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L. Håglin1, L. Bäckman1, J. Linder2, L. Forsgren2, M. Domellöf2,3


1. Department of Public Health and Clinical Medicine, Family Medicine, Umeå University, SE-901 87 Umeå, Sweden; 2. Department of Pharmacology and Clinical Neuroscience, Umeå University, SE-901 87 Umeå, Sweden; 3. Department of Psychology, Umeå University, SE-90187 Umeå Sweden

Corresponding Author: L Håglin, Department of Public Health and Clinical Medicine, Family Medicine, Umeå University, SE-901 87 Umeå, Sweden, lena.haglin@umu.se

J Aging Res Clin Practice 2018;7:156-162
Published online November 19, 2018, http://dx.doi.org/10.14283/jarcp.2018.26



Background: Cognitive decline and dementia are common non-motor problems in Parkinson’s disease (PD). The underlying aetiology is multifaceted and both chronic and reversible causes for cognitive decline are likely to be present. Malnutrition is frequent in the Parkinson population, both early and late in the disease, and nutritional deficiencies could play a role in some cognitive deficits. Objectives: The objective is to study the association between nutritional status with focus on iron intake and homeostasis, mild cognitive impairment (MCI), and PD dementia (PDD). Setting and Participants: This study included 73 out of 145 patients with PD participating in a population-based study in northern Sweden. Measurements: Registration of nutritional status by laboratory analyses of blood plasma and neuropsychological assessments at time of diagnosis were performed. MCI and PDD were assessed yearly up to ten years after diagnosis. Mini Nutritional Assessments (Full-MNA score) and plasma variables detecting iron homeostasis were compared between patients with MCI and patients with normal cognition (NC). Motor severity was measured using the Unified Parkinson´s disease rating scale III, (UPDRS III) and Hoehn and Yahr (H&Y) staging scale. Cox proportional Hazard model were performed to see if any variables that differed between MCI and NC could predict PDD at follow-up. Results: Patients with MCI at time of diagnosis had lower levels of plasma iron (P-Fe) and albumin (P-Albumin) as well as a lower score on Full-MNA score. Dietary intake of iron was higher in patients with MCI than in patients with NC (p = 0.012). In logistic regression models adjusted for age, sex, and UPDRS III, lower levels of P-Fe (p = 0.025) and P-Albumin (p = 0.011) and higher dietary iron intake (p = 0.019) were associated with MCI at baseline. A Cox regression model with dementia as endpoint revealed that lower levels of P-Fe increase the risk of dementia at follow-up with adjustments for age, sex, UPDRS III, and MCI at baseline (HR 95% CI = 0.87 (0.78-0.98), p = 0.021). Conclusions: Low P-Fe was associated with cognitive disturbance at baseline and predicted dementia up to ten years after diagnosis in patients with PD. Low P-Albumin and malnutrition assessed with Full-MNA score were associated with MCI at baseline but did not predict dementia at follow-up.

Key words: Cognition, dementia, iron deficiency, Parkinson’s disease.




Parkinson’s disease is a complex multifaceted disease with great variations in prognosis. Predicting the path the illness will take is next to impossible. Therefore, it is important to find predictors for different disease outcomes.
Cognitive decline and dementia are common non-motor problems in PD and the incidence of dementia is two to six times higher than in the general population (1).
At diagnosis, 20-40% of the populations have Mild Cognitive Impairment (MCI) (2 – 5). MCI at diagnosis increases the risk of Parkinson’s disease dementia (PDD), but not all patients with MCI develop dementia (5). Different patterns of cognitive decline have been connected to PDD. For example, impairment of semantic fluency and pentagon copying has repeatedly been shown to predict PDD (5,6). Low education level, postural instability, UPDRS (7), impaired olfactory function (8,9), and male sex has been connected to higher rates of PDD (10).
Cognitive impairment has been reported among elderly with malnutrition and iron deficiency (11, 12). Solfrizzi et al. (2006) presented a review on the nutrient-dementia risk pattern and suggested that more studies were needed to support the role of metals in progression of cognitive decline (13). A high iron intake has frequently been reported to increase the risk of PD, but no convincing evidence exists for an association between PDD and intake of iron. Cheng et al. (2011) reported that PD risk increased by 18% (RR 1.18, 95 % CI 1.02-1.37) by every 10-mg/day increment in iron intake (14). Powers et al. (2003) reported that a high intake of iron, especially in combination with high manganese intake, may be related to an increased risk of PD (15). In addition, Powers et al. (2009) reported that high iron intake together with a low intake of cholesterol may be associated with an increased risk of PD (16). On the contrary, a higher intake of iron, magnesium, and zinc was independently associated with a reduced risk of PD (17). Follow-up of two large cohort studies, including accumulated information on nutrient intake, revealed a higher risk of PD with a high intake of non-heme iron in combination with low vitamin C intake, while not with intake of heme iron (18).
This study investigated the association between nutritional status with a focus on iron intake and homeostasis in PD patients at time of diagnosis and risk of MCI and PDD at follow-up.




This community-based prospective study focuses on idiopathic forms of Parkinsonism in a catchment area (parts of Västerbotten county in northern Sweden) with 142 000 inhabitants (19). All suspected cases with idiopathic Parkinsonism were referred to the neurological department that employed all the neurologists involved in this investigation. From January 2004 through April 2009, 185 cases with Parkinsonism were identified. In total 145 patients fulfilled diagnostic criteria for PD at the next follow-up (up to 10 years). Of these, 73 were included in the study (Table 1). Because the remaining 72 non-participating patients came to follow-up without fulfilling the three-day dietary registration, they were not included for a blood sample. Individuals not participating in the three-day dietary registration were older (mean 73.5 years vs mean 69.1 years, p=0.006) and scored higher on the UPDRS III (29.2 vs 24.7 p=0.016) compared to those participating. There were no significant differences between the groups with regard to proportions of men and woman, total MMSE and MNA score.
A few patients refused to participate and were classified as drop outs. All participants were extensively examined during repeated visits the first month following initial contact. Information about demographics and disease history was obtained. All cases with suspected idiopathic Parkinsonism underwent a standardized clinical examination by a neurologist specializing in movement disorders.
To confirm the presence of PD, another specialist in movement disorders (blinded to the assessment of the previous examiner) evaluated a videotape of the patient undergoing the UPDRS III examination investigating PD related motor functions speech, facial expression, rigidity, tremor, posture, gait and bradykinesia (20). Patients were included if both examiners judged that they had fulfilled the clinical criteria for PD according to the UK Parkinson ’s Disease Society Brain Bank (UK PDSBB) criteria. Motor severity was measured using the Unified Parkinson´s disease rating scale III, (UPDRS III) and Hoehn and Yahr (H&Y) staging scale.

Table 1 Baseline variables (mean±sd) for the total PD group and for patients with Mild Cognitive Impairment (MCI) and Normal Cognition (NC). P-values as a result from comparing variables between MCI and NC

Table 1
Baseline variables (mean±sd) for the total PD group and for patients with Mild Cognitive Impairment (MCI) and Normal Cognition (NC). P-values as a result from comparing variables between MCI and NC

Abbreviations: UPDRS = Unified Parkinson’s Disease Rating Scale; H&Y = Hoehn & Yahr stage, median; ADL = Activity of daily living; PIGD = Postural instability Gait Disorder; Ind = Indeterminate; TD = Tremor dominance:


The UPDRS scoring was performed with patients on their regular medication when started on dopaminergic treatment. The motor subtype was classified as tremor dominant (TD), postural instability and gait difficulty (PIGD) or indeterminate (Ind) according to Jancovic et al (21). The MMSE was used as a screening instrument for global cognition.
The study was approved by the Regional Medical Ethics Board in Umeå, Sweden. Written informed consent was obtained from all participants.

Medication for PD

The levodopa equivalent daily dose (LEDD) was calculated at baseline and at follow-ups by use of a conversion factor for each of the anti-Parkinson medications (22). Information about LEDD at baseline revealed that only two patients had started anti-Parkinson treatment at time of diagnosis. At first follow-up (six months), all but nine patients had started treatment and about 50% of the patients had a LEDD <200 and 8% had >300. Medication was introduced over the first weeks after diagnosis. The nutritional investigation, including the blood sampling, was performed in a non-standardized manner according to drug therapy during this time. Thirteen patients started anti-Parkinson medication before the blood sampling.

Nutritional assessments

The Full Mini-Nutritional Assessment (MNA score), an international validated screening tool, was used to assess nutritional status and performed by the dietician concomitantly with anthropometrical measurements. The screening consists of 18 questions regarding anthropometry, diet, and health (23). MNA total scores between 24 and 30 points indicate optimal nutritional status and scores between 17 and 23.5 points indicate at risk for malnutrition.
Dietary data were collected from a three-day dietary registration (3-day DR) performed by the patients three days before a scheduled visit to the Department of Neurology. The subjects recorded in a protocol what they ate and drank during those three days. To describe portion sizes, they had access to a booklet with photographs and drawings of various foods and dishes. Standard household measures or package sizes were used for food items not included. Energy and nutrient intake were calculated using the dietary software program Dietist XP (Kost och näringsdata, Stockholm, Sweden), which employs the National Food Administrations food database (NFA database 2.00, Uppsala, Sweden).

Biochemical analysis

Blood samples at baseline were collected at admittance between 8 am and 4 pm in a non-fasting condition on the day when the patients were admitted for assessments of nutritional status. Plasma samples were collected and stored at -70◦C until iron, ferritin, albumin, and transferrin were measured. Transferrin saturation was calculated S-Fe [µmol/L] x 100 / (S-Transferrin [g/L] x 25.1) (Trf %). Analysis was performed in clinical routine in the accredited laboratory at Umeå University Hospital. Plasma levels of albumin and transferrin were analysed by Vitros PHOS Slides, Vitros ALB Slides, and Vitros TRFRN reagent on an Ortho Vitros 5.1 FS analyser.


A battery of neuropsychological tests was performed and used for MCI and PDD classification at baseline, one year, three years, five, eight, and ten years. For MCI classification, the MDS Task force guidelines were used (24). Since the battery of tests included a minimum of two tests in all domains except language, modified level II criteria were applied (25). For patients not performing the full neuropsychological testing, MCI classification was based on self-perceived cognitive decline and MMSE (cut-off ≤29) (26).  All but four patients with blood samples performed the neuropsychological evaluation at baseline. PDD was diagnosed according to published criteria by neurologists experienced in neurodegenerative disorders (27). In periods between the neuropsychological testing, PDD was diagnosed by decline in MMSE, decline in basic activities of daily living (ADL) (28) due to decreased cognition, and cognitive decline reported from patients and/or family member. In addition to MCI and PDD, composite scores for different cognitive domains (executive function, attention, language, visuospatial function, and episodic memory) were calculated based on means of the z scores for each individual test. Neuropsychological measures used for classification of Mild Cognitive Impairment and calculation of composite scores. Pentagon copying was not included in the calculation of composite scores.
Episodic memory: Free and Cued Selective Reminding Test (FCSRT) free recall, Brief Visuospatial Memory Test (BVMT) total, Brief Visuospatial Memory Test (BVMT) delayed.
Visuospatial function: Benton Judgement of Line Orientation (BJOLOT), pentagon copying from MMSE. Language function: Boston Naming Test. Working memory and attention: Digit span backwards, Trail Making Test part B. Executive function: Wisconsin Card Sorting Test (WCST) total errors, Wisconsin Card Sorting Test (WCST) preservative errors, Semantic fluency (animals in 60 seconds).

Data analyses

The results are presented as mean and standard deviation with min-max for each variable presented. Independent two-tailed tests were used to compare patients with MCI and NC. For non-normal distributed data and variables with skewed distribution, non-parametric tests were performed: the Mann-Whitney and the Wilcoxon Signed Ranks Test. Most variables were approximately normally distributed except for H&Y score, P-Ferritin, and dietary iron intake. Because of the non-normal distribution, P-Ferritin and dietary intake of iron were dichotomized by the median value (P-Ferritin median = 128.7 µg/L and dietary iron intake median = 9.77 mg/day).
To check whether the variables that significantly differed between MCI and NC independent of age, sex, and UPDRS III, logistic regression models adjusted for age, sex, and UPDRS III were performed. To investigate the specific cognitive domains (i.e., the association with the variables differing between patients with MCI and patients with NC), partial correlations was used with corrections for age, sex, and UPDRS III with the biochemical assessments and merged scores for the separate cognitive domains.
The Cox proportional hazards model was used to study the association between biochemical assessments at baseline and the development of PDD. Variables associated with MCI were included in Cox-regression models, first univariate, and then multivariate adjusted for age, gender, UPDRS III at baseline, and finally MCI at baseline was added.
The program Predictive Analytics Software (SPSS Statistics, version 24 SPSS Inc., Chicago IL, USA) was used for the analysis.



Baseline data

Non-motor and motor functions assessed at baseline for patients with PD (n=73) and for patients with MCI (n=30) and NC (n=43) are presented in Table 1. At baseline, MCI was more prevalent in males than in females and was associated with older age, lower level of education, and higher UPDRS III score. Patients with MCI had higher daily intake of iron and lower MNA score, P-Albumin, and P-Fe before adjusting for age, sex, and UPDRS III (Table 2). After adjusting, the OR for having MCI was still significant for P-Albumin, P- Fe and daily intake of iron but not for MNA score (Exp B: 95% CI = 0.799 (0.672-0.950), p = 0.011), P-Fe (Exp B: 95% CI = 0.854 (0.744-0.980), p = 0.025), dietary iron intake (Exp B: 95% CI = 4.425 (1.54-18.9) p = 0.019), and MNA score (Exp B: 95% CI = 0.79 (0.984-1.125, p = 0,057, respectively) (Table 2). Biochemical and nutritional assessments for males and females, including variables for iron homeostasis, are presented in Table 3. Males had higher P-Ferritin and dietary iron intake than females. No other differences indicate sex dependent disturbed iron homeostasis and nutritional status.


Table 2 Baseline variables (mean±sd) used to assess iron status in PD patients with Mild Cognitive Impairment (MCI) and Normal Cognition (NC). The level of significance from the logistic regression with adjustments for age, sex, and UPDRS III are presented in the right column

Table 2
Baseline variables (mean±sd) used to assess iron status in PD patients with Mild Cognitive Impairment (MCI) and Normal Cognition (NC). The level of significance from the logistic regression with adjustments for age, sex, and UPDRS III are presented in the right column

* Plasma ferritin and dietary iron intake were dichotomized to over and under median value (median=128.7 μg/L and median = 9.77 mg/day respectively) As seen in table 3. Abbreviations: TrF % = S-Fe [µmol/L] x 100 / (S-Transferrin [g/L] x 25.1); MNA = Mini Nutritional Assessment.


Correlations between P-Albumin and neuropsychological tests

Composite scores of working memory correlated with P-Albumin levels (r = 0.452, p < 0.001) and P-Ferritin levels (r=270, p=0.025).   Both correlations were stronger for males than females: P-Albumin (male; r = 0.549, p < 0.001 and female r = 0.331, p = 0.069 (Figure 1), P-Ferritin (male; r = 0.413, p = 0.01 and female r = 0.212, p = 0.252)  Composite scores of episodic memory correlated with P-albumin (r = 0.253, p = 0.036). After adjusting for age, gender, and UPDRS III score in partial correlations, the positive association between composite score of working memory and P-Albumin (r = 0.346, p = 0.004) and P-Ferritin (r = 0.309, p = 0.012) remained significant.

Table 3 Baseline variables in mean±sd and for min-max used to assess iron status in patients with PD

Table 3
Baseline variables in mean±sd and for min-max used to assess iron status in patients with PD

* Plasma ferritin and dietary iron intake were dichotomized to over and under median value (median=128.7 µg/L and median = 9.77 mg/day respectively); Abbreviations: TrF % = S-Fe [µmol/L] x 100 / (S-Transferrin [g/L] x 25.1); MNA = Mini Nutritional Assessment.


Figure 1 P-Albumin levels correlated with composite score of working memory and were stronger for males than females (male: r = 0.549, p < 0.001 and female: r = 0.336, p = 0.064)

Figure 1
P-Albumin levels correlated with composite score of working memory and were stronger for males than females (male: r = 0.549, p < 0.001 and female: r = 0.336, p = 0.064)


Cox regressions in prediction of PDD

Results from Cox regression analysis are shown in Table 4. Lower baseline P-Fe (µmol/L) and P-Albumin (g/L) levels increased the risk of PDD at follow-up in univariate models. In models controlling for age, sex, and UPDRS III, lower levels of P-Fe significantly increased the risk of PDD (HR (95% CI) = 0.85(0.76-0.94), p = 0.002). Adding MCI to the model did not affect the higher risk of PDD with lower P-Fe levels (HR (95% CI) = 0.87(0.78-0.98), p = 0.02).

Table 4 Results from Cox regression (HR 95% CI) with Dementia as outcome variable and nutritional variables as explanatory included are presented with bivariate and multivariate calculations

Table 4
Results from Cox regression (HR 95% CI) with Dementia as outcome variable and nutritional variables as explanatory included are presented with bivariate and multivariate calculations

*Adjusted for age, sex, and UPDRS III. ** Adjusted for age, sex, UPDRS III, and MCI; Iron intake was dichotomized to over and under median value (9.77 mg/day); Abbreviations: MNA = Mini Nutritional Assessment.



The main finding from our study is that low levels of P-Fe were associated with MCI at time of diagnosis and increased risk of dementia over 10 years, while neither intake of iron, MNA-score, nor P-Albumin predicted dementia at follow-up. In addition, significantly lower levels of P-Albumin and lower score on Full MNA, indicating risk of malnutrition, and higher dietary intake of iron were seen in patients with PD-MCI at time of diagnosis. With adjustments for age, sex, and UPDRS III, the difference was maintained only for P-Albumin and dietary intake of iron.

Lower levels of P-Albumin, P-Fe, and Full MNA score at diagnosis for patients with MCI indicate malnutrition, which may have had its origin years prior to diagnosis and first symptoms. An association between MNA score and MCI in older in-patients (29) and between MNA score and disease severity and progress of disability in patients with PD has been reported (30,31). Nutritional status may be affected by several of the disease-related measurements such as ADL, UPDRS, and medication.
Used at baseline to assess malnutrition, the MNA score was lower in patients with MCI compared to patients with NC, but it did not predict PDD at follow-up. Different components of nutritional status besides results from a screening test may have importance when focusing on risk of dementia progression (32). However, MNA score has been shown to correlate with P-Albumin and dietary intake of iron (33). Being malnourished and having MCI may also have contributed to low P-Fe levels and may be one of several components of nutritional status that can influence progress to PDD. Difficulties in eating abilities and cutting food, often reported in PD patients, can result in a low intake of nutrients and energy. Age, disease, and sex-related factors also contribute to the consequences of malnutrition. In addition to finding predictors for different disease outcomes at the time of diagnosis, we also need to focus on finding PDD predictors already in the prodromal phase of PD.
In the present study, P-Albumin was significantly lower in patients with MCI than in patients with intact cognition at baseline. Albumin has previously mostly been associated with mortality and aging (34,35,36), although a handful studies have found an association of low levels of P-Albumin with cognitive decline (37,38). The different P-Albumin levels between MCI and NC were still significant after controlling for age and disease severity, which indicates that P-Albumin has a specific connection to cognitive decline. Also, the correlation between P-Albumin and P-Ferritin within normal limits and working memory was stronger in men than in woman, which suggests a sex difference for the impact of P-Albumin and P-Ferritin levels on working memory. No studies have reported this association before. As several comparisons were performed, the results may be spurious. Had we applied Bonferroni correction, only P-Albumin would have been considered significantly different between MCI and NC. Frangos et al. (2016) concluded that both age and disease contribute to low albumin, which could explain low haemoglobin levels in malnourished associated anaemia in very old hospitalized elderly (39). The baseline levels of P-Albumin and MNA score indicate an early association with cognitive decline in patients with PD in our study population.
Haemoglobin analysis was not performed on the same occasion/visit with blood sampling and assessment of malnutrition, limiting the possibility to assess anaemia. However, iron deficiency may be important for cognitive function independent from anaemia. Yavuz et al. (2012) studied geriatric patients (mean 72 years of age) and concluded that iron levels and Trf % independently correlated with MMSE. In that study, patients with dementia had low Trf % and a low MMSE associated with iron deficiency (11). Mean levels for P-Transferrin increase to compensate for low P-Fe and increased need, but in our study mean levels for P-Transferrin decreased with malnutrition. P-Fe is transported with transferrin, and about 30-40% of this capacity is used dependent on age and sex and increases after the age of 70 years (40,41). Besides being an iron transporter, P-Transferrin is a marker for nutritional status (42,43). By a shorter half-life than albumin, transferrin may be a strong marker for protein energy malnutrition within days to weeks.
Iron deficiency may affect dopamine metabolism (44,45), and dysregulation of iron metabolism has been described as a risk factor for PD (46). Iron homeostasis is reported to be important for cognition (47). Cognitive impairment has been reported among elderly with iron deficiency and malnutrition (11,12).  Iron deficiency in adults and elderly indicates that age and sex may have contributed to hypo-metabolism that might have resulted in early dementia in Parkinson’s disease (48). In the present study, age was associated with both MCI at baseline and with increased risk for dementia over 10 years. The vicious circle with ageing, malnutrition, and cognitive decline may be even stronger in PD patients due to disease-related disturbances than in a non-PD elderly population. A low bioavailability of iron in the intestine (the main cause of iron deficiency, at least among elderly) could have generated the low P-Fe in the present population of patients, for example, due to gastrointestinal disturbances like gastro pares and achlorhydria (49). The level of P-Fe varies from day to day and low levels indicate either low intake or malabsorption. The risk of MCI, associated with either high intake of iron or low plasma Fe, indicate the importance of intestinal function for maintaining iron homeostasis. A high intake of iron may affect bioavailability of other minerals and thereby contribute to deficit cognition. To study influence from dietary intake, more information on nutrient density in general and individual energy intake are needed together with data on intestinal function and medication. Reporting dietary intake may also have been affected by the level of cognitive ability.



Our results indicate that low P-Fe was associated with MCI at baseline and increases risk for dementia up to 10 years after diagnosis of PD. Low P-Albumin and disturbed cognition in PD may influence the progression to dementia and be a sign of protein energy malnutrition. High intake of iron increased the risk of MCI at baseline but did not show any effect on PDD risk. We suggest that low P-Fe in our sample might be related to a disturbed regulation, including intestinal absorption in iron metabolism as well as malnutrition.


Funding: This study was funded by The Swedish Parkinson Foundation (Svenska Parkinsonstiftelsen), Swedish Parkinson foundation, Neuro Sweden, The Swedish Parkinson Disease Association, The Swedish Medical Research Council and Västerbotten County Council (ALF).

Conflict of interest: The authors declared that they had no conflict of interests.

Ethical Standard: The study was approved by the Ethics Committee of the Faculty of Medicine at Umeå University. Written, informed consent was obtained from all participants.



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M. Muscat1, C. Scerri2


1. Department of Gerontology, Faculty for Social Wellbeing; 2. Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta MSD 2080.

Corresponding Author: Charles Scerri PhD, Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida MSD 2080, Malta; Tel.: +356 23402905; Fax: +356 21320281; E-mail: charles.scerri@um.edu.mt

J Aging Res Clin Practice 2018;7:128-135
Published online October 15, 2018, http://dx.doi.org/10.14283/jarcp.2018.22



Objective: This study aimed to investigate how informal primary caregivers of individuals with dementia living in the community cope with caring-related measures of anxiety, depression, burden and quality of life. Participants and Design: Participants included 60 informal caregivers (23 males and 37 females) of community-dwelling individuals with dementia who attended a state-run geriatric day hospital in Malta. Caregiver measures included the Hospital Anxiety and Depression Scale, the World Health Organization Quality of Life–BREF and Brief COPE questionnaires, and Zarit Burden Interview. The Mini Mental State Examination and Barthel Index of Activities of Daily Living scores were used to determine the degree of cognitive impairment and performance in activities of daily living of care-recipients. Results: Informal caregivers experienced anxiety and depression with both emotional distress states negatively affecting all quality of life domains. Depression and burden experienced by informal primary caregivers showed a strong association with individuals with dementia-related variables such as age, cognitive impairment and activities of daily living scores. The use of dysfunctional coping strategies was found to be related to caregivers’ emotional distress, low quality of life and burden. Conclusion: The findings indicate that informal primary caregivers experienced anxiety and depression, had a lower quality of life, and feel burdened during their caring role. However, caregivers making use of emotion-focused coping strategies were found to be protected against emotional distress. The results highlight the need of providing support services aimed at promoting the psychological wellbeing of informal carers of community-dwelling individuals with dementia.

Key words: Caregiver, coping, dementia, emotional distress, quality of life.



Dementia is a clinical term referring to a group of brain disorders characterized by progressive deterioration of cognitive abilities. In 2015, it was estimated that 1.5% of the population in Malta had dementia, a figure that is projected to more than double in the next 30 years (1). This, in conjunction with a demographic shift favouring a progressive increase in the elderly population, will add to a growing burden on family members who, in the majority of cases, provide informal care for these individuals at home (2).
At present there is no cure for the most common forms of dementia and consequently the main focus lies in promoting the wellbeing and providing optimal quality of life for the individual with dementia and their caregivers (3). Previous research has demonstrated that high levels of neuropsychiatric symptoms in dementia caregivers leads to a reduction in their quality of life (4) and caregiver burden is mostly related to the caregiver ability to cope with the situation (5). A number of coping strategies and styles adopted by dementia caregivers have been proposed with those based on emotional support and problem-focused strategies being associated with caregiver wellbeing and positive outcomes (6-8).
The main objective of this study was to investigate how coping strategies and styles used by informal primary caregivers caring for an individual with dementia living in the community influence their levels of anxiety, depression, burden and quality of life. This category of caregivers was selected as previous research have shown that, in Malta, rather than resorting to institutionalization of the person with dementia, a unique model of care based on reliance on families through a rotation pattern of care by different family members is preferred (2).  Therefore, the identification of predictive factors that enhance the wellbeing of caregivers of individuals with dementia living in the community would not only ensure that health and social support programmes are designed to meet the desired needs but would further delay institutionalization of the care-recipient (9).



The study was conducted in Malta from early January to the end of May 2015. Participants were informal primary caregivers of individuals with dementia attending a state-run geriatric day hospital who had received a formal diagnosis of dementia by a medical specialist. A convenience sample of caregivers (n = 74) was selected with selection criteria being attendance to the day hospital by the individuals with dementia, individuals with dementia living in the community, caregiver residing in the same or separate household and being the primary care provider. Participants were contacted by telephone following which 60 agreed to take part in the study. Sociodemographic data of caregivers included age, gender, occupation, relationship with individuals with dementia, marital status, level of education, whether they were living with the individuals with dementia, duration of caregiving in years, number of contact hours per day and whether they were formally diagnosed with anxiety/depression during their caregiving role. Information on individuals with dementia included age, gender and dementia type. The levels of cognitive impairment and activities of daily living of individuals with dementia were based on the  Mini Mental State Examination (MMSE) (10) and Barthel Index of Activities of Daily Living (BI-ADL) (11) scores measured by a geriatric medical specialist prior to study commencement.
The research instruments used in assessing caregivers included the Hospital Anxiety and Depression Scale (HADS), the World Health Organization Quality of Life–BREF (WHOQOL-BREF) and Brief COPE questionnaires, and Zarit Burden Interview (ZBI). The HADS consists of two seven–item subscales, one related to anxiety and the other to depression (12). Each item carries a four-point scale (0-3) with the total possible score for both anxiety and depression ranging from 0-21. Scores are categorized as normal (0-7), mild (8-10), moderate (11-14) and severe (15-21). The WHOQOL-BREF comprises 26 items grouped under domains for physical health, psychological health, social relationships and environmental health (13). Each item is rated on a 5-point Likert scale with higher scores denoting better quality of life. The Zarit Burden Interview consists of 22 items with a 5-point Likert scale ranging from 0 (never) to 4 (nearly always) (14) whereas the Brief COPE measures a number of different coping strategies and consists of 14 subscales with two questions per style with a 4-point Likert scale ranging from 1 (I haven’t been doing this at all) to 4 (I’ve been doing this a lot) (15). The coping strategies are divided into 3 domains: emotion-focus (use of emotional support, positive reframing, acceptance, religion, humour), problem-focus (active coping, planning, use of instrumental support) and dysfunctional coping (venting, denial, substance use, behavioral disengagement, self-distraction, self-blame) (16).
All interviews with informal primary caregivers were carried out face-to-face in English language at the participants’ residence. The study was approved by the Faculty of Social Wellbeing Ethics Committee and the Research Ethics Committee of the University of Malta. Permission was also granted by the management of the day hospital. Participants were guaranteed confidentiality and anonymity and were free to withdraw at any stage of the interview without giving a reason. Written consent was obtained from all participants. Depending on cognitive impairment, consent from individuals with dementia was obtained either directly or by proxy.
Descriptive statistics were used to summarize sociodemographic and clinical data of participants as percentages, means and standard deviation (SD). Relationships between anxiety, depression, quality of life, burden and coping scores with sociodemographic characteristics and clinical data were analysed using Student’s t-test for two groups of data and one factor ANOVA with post hoc comparisons using Tukey for multiple groups. In the event that the data were not normally distributed as determined by the Shapiro-Wilk test, the Mann-Whitney U test was applied.
To study the degree to which anxiety and depression, quality of life and burden experienced by caregivers was related to their coping strategies and styles, the Pearson’s correlation coefficient (r) analysis was conducted. All research instruments used for caregivers’ measures were assessed for internal consistency using the Cronbach’s alpha test. Data analysis was conducted using PASW Statistics (version 20.0) with significance level set at 0.05.



Characteristics of participants

Descriptive characteristics of individuals with dementia and their informal primary caregivers are presented in Table 1. Care-recipients had a mean age of 77.5 years (range: 46 – 92) and showed moderate functional dependency levels. With respect to the severity of cognitive function, 36.7% had mild, 25.0% moderate and 38.3% severe cognitive impairment. A significant positive correlation was observed between MMSE and BI-ADL (r = 0.801, p < 0.001) indicating that individuals with dementia having severe cognitive impairment were the most functionally dependent.
Informal primary caregivers were mostly females, married, had a secondary level of education, unemployed and living in the same household. The duration of caregiving role varied from 1 to 25 years with an average of 4.5 years whereas the average number of contact hours spent in daily caregiving was 16.2 hours. A third of participants indicated that they spend 24 hours per day in their caregiving role.

Table 1 Sociodemographic characteristics and clinical data of individuals with dementia and their informal primary caregivers (AD, Alzheimer’s disease; BI-ADL, Barthel Index of Activities of Daily Living; ipCG, informal primary caregiver; IWD, individual with dementia; LBD, Lewy-body dementia; MMSE, Mini-Mental State Examination; VaD, vascular dementia)

Table 1
Sociodemographic characteristics and clinical data of individuals with dementia and their informal primary caregivers (AD, Alzheimer’s disease; BI-ADL, Barthel Index of Activities of Daily Living; ipCG, informal primary caregiver; IWD, individual with dementia; LBD, Lewy-body dementia; MMSE, Mini-Mental State Examination; VaD, vascular dementia)


Informal primary caregivers’ anxiety and depression

The mean anxiety score for caregivers was found to be significantly higher than the mean depression score (F = 8.594, p < 0.001) denoting that caregivers experienced more anxiety than depression during their caring role (Table 2). Furthermore, anxiety and depression were found to be significantly correlated (r = 0.777, p < 0.001) indicating that caregivers with high anxiety scores tended to have higher levels of depression. Caregivers who had a lower level of education, cared for individuals with dementia with low cognitive and functional scores, and formally diagnosed with anxiety/depression during the caregiving role experienced higher levels of anxiety and depression.

Table 2 Relationship between anxiety, depression, quality of life and burden scores with sociodemographic characteristics and clinical data of individuals with dementia and their informal primary caregivers (α, Cronbach’s alpha; BI-ADL, Barthel Index of Activities of Daily Living; ipCG, informal primary caregiver; IWD, individual with dementia; MMSE, Mini-Mental State Examination)

Table 2
Relationship between anxiety, depression, quality of life and burden scores with sociodemographic characteristics and clinical data of individuals with dementia and their informal primary caregivers (α, Cronbach’s alpha; BI-ADL, Barthel Index of Activities of Daily Living; ipCG, informal primary caregiver; IWD, individual with dementia; MMSE, Mini-Mental State Examination)


Informal primary caregivers’ quality of life

As indicated in Table 2, caregivers who were employed, had a post-secondary level of education and have not been formally diagnosed with anxiety/depression during their caregiving role had higher quality of life scores. Amongst the domains tested, the two highest average standardised scores were reported for the environment and psychological domains with social relationships scoring the lowest. The social relationships domain was found to be significantly correlated with the age of the individual with dementia (r = 0.264, p = 0.042) and caregiver (r = -0.277, p = 0.032) and related to whether the caregiver was living in the same household, relationship with the individual with dementia and the educational status of the caregiver. The latter was also found to similarly affect the environment domain.

Informal primary caregivers’ burden

Approximately half of the caregivers participating in this study (46.7%, n = 28) indicated that they experienced moderate to severe/severe burden whilst caring for an individual with dementia. A significant inverse correlation was found between the age of the individual with dementia and the burden score (r = -0.299, p = 0.020) suggesting that the younger the individual with dementia, the greater the burden on the caregiver. A low BI-ADL score and a formal diagnosis of anxiety/depression in the caregiver were also found to be significantly related to higher caregiver burden (Table 2).

Informal primary caregivers’ coping strategies

The mean rating scores for emotion-focus and problem-focus strategies were similar and significantly higher than dysfunctional coping (p < 0.001) denoting that the latter was the coping strategy that was used the least by the caregivers (Table 3). Moreover, dysfunctional coping was inversely correlated with the age of the care-recipient (r = -0.268, p = 0.038) and significantly related to the increasing number of hours/day spent in caring and the presence of a formal diagnosis of anxiety/depression in the caregiver. Out of the 14 coping styles, the most frequently used were acceptance and active coping with substance abuse scoring the lowest.

Table 3 Relationship between coping strategies and styles with sociodemographic characteristics and clinical data of individuals with dementia and their informal primary caregivers. Cronbach’s α for the Brief COPE = 0.713 (BI-ADL, Barthel Index of Activities of Daily Living; ipCG, informal primary caregiver; IWD, individual with dementia)

Table 3
Relationship between coping strategies and styles with sociodemographic characteristics and clinical data of individuals with dementia and their informal primary caregivers. Cronbach’s α for the Brief COPE = 0.713 (BI-ADL, Barthel Index of Activities of Daily Living; ipCG, informal primary caregiver; IWD, individual with dementia)


Association between informal primary caregivers’ measures of anxiety and depression, quality of life, burden and coping strategies and styles

In informal primary caregivers, higher levels of both anxiety and depression were found to be related to a reduction in the overall quality of life and increased burden (Table 4). Furthermore, caregivers who were using dysfunctional coping strategies experienced higher levels of anxiety and depression. The latter were also found to be positively correlated with the coping styles of planning, behavioral disengagement, denial and self-blame. Conversely, the use of acceptance, positive reframing and self-distraction were related to diminished emotional distress. Caregivers who reported high levels of burden had lower quality of life scores with all domains being affected except physical health. Burden scores were also found to be high in caregivers adopting dysfunctional coping strategies with relationships to coping styles similar to those reported for anxiety and depression.

Table 4 Correlations between anxiety, depression, quality of life, burden and coping strategies and styles of informal primary caregivers of individuals with dementia (WHOQOL-BREF, World Health Organization Quality of Life-BREF; ZBI, Zarit Burden Interview). Only significant Pearson correlation coefficient (r) values reported (* P < 0.05, ** P < 0.01, *** P < 0.001)

Table 4
Correlations between anxiety, depression, quality of life, burden and coping strategies and styles of informal primary caregivers of individuals with dementia (WHOQOL-BREF, World Health Organization Quality of Life-BREF; ZBI, Zarit Burden Interview). Only significant Pearson correlation coefficient (r) values reported (* P < 0.05, ** P < 0.01, *** P < 0.001)



To the best of our knowledge, this is the first investigation that explored anxiety, depression, burden, quality of life and coping strategies used by informal primary caregivers of community-dwelling individuals with dementia in Malta. Determining the psychological wellbeing and type of coping strategies adopted by this category of caregivers could aid in developing community services that address their needs. This is in agreement with the Call for Action adopted by the First WHO Ministerial Conference on Global Action Against Dementia that emphasised that policy interventions should be sensitive to the specific needs of people living with dementia and their caregivers (17).
The findings reported here showed that more than half of participating caregivers experienced anxiety and with a quarter feeling depressed. Similar to other findings (18, 19), caregivers having higher levels of education scored significantly lower in anxiety and depression possibly indicating that education might act as a protective effect. Of note was the absence of depression in the two-thirds of informal primary caregivers. People caring for individuals with dementia respond to depression in different ways and at different times. They might experience emotional distress soon after diagnosis of dementia in their relative, whereas in others as dementia progresses to its severe stage and the duration of care increases (20). However, the latter was not supported by the present findings in which the levels of anxiety, depression, burden and quality of life in informal primary caregivers were not found to be related to the number of years and number of hours per day spent in caregiving. Even though most caregivers participating in this study appeared to experience lower levels of depression, more research is needed to determine how the changing course of dementia might impact the caregiver emotional response in the local context.
Factors that strongly impacted caregiver burden in this study were the younger age of the individual with dementia, loss of functional status and a formal diagnosis of anxiety and depression in the caregiver. Although caregivers taking care of an individual with dementia with greater functional dependency experienced higher burden levels, no association between burden and patient cognitive scores was found possibly suggesting that deterioration in individuals with dementia abilities to take care of themselves leads to higher caregiver burden compared to cognitive deterioration. Similar trends were observed in other countries in which the direct influence of patients’ cognition on caregiver burden is limited with the patients’ functional abilities being the main predictor for burden (21). Contrasting previous data (22, 23), the age of the caregiver was not found to be related to burden. Rather, the age of the care-recipient showed a significant effect, with a younger age associated to higher caregiver burden. This is not surprising considering that young individuals with dementia pose additional challenges on their primary caregivers such as lack of appropriate access to specialized care as well as work and additional family commitments (24).
In caregivers, dysfunctional coping strategies were found to be significantly related to anxiety and depression, the duration of caregiving and the age of the care-recipient. Emotion-focus coping strategies, with coping styles that included acceptance and positive reframing, were preferred by the majority of caregivers and this may have contributed to a reduction in the anxiety and depression scores. Conversely, dysfunctional coping was mostly related to an increase in caregiver burden. Of note was that positive reframing coping style, in which stressful events are redefined in order to make them manageable (25), showed a significant correlation with emotional distress status, quality of life and caregiver burden. The ability to use this coping style in the present study was possibly related to the cohort cultural context, in which dementia care is a family affair and a shared care arrangement between family members as a form of respite is the norm (2).
The current study has a number of limitations. The WHOQOL-BREF instrument was not specifically developed for caregivers of individuals with dementia, although there are precedents for its use in this population (26). The study made use of individuals with dementia and their informal primary caregivers attending a day hospital which may not be representative of the dementia caregiver population in Malta. Sample selection was not randomised and thus the possibility of selection bias cannot be excluded. The modest sample size may have also limited statistical power.
In conclusion, the results reported here indicate that informal primary caregivers of individuals with dementia living in the community are more likely to suffer from emotional distress, experience burden and have a lower quality of life. However, those caregivers who use emotion-focused strategies were found to be protected against emotional distress. This continues to highlight the need of identifying multi-component interventions that support informal caregivers in maintaining a lifestyle that improves their quality of life. Knowing that in Malta dementia care in the community mostly follows a shared familial arrangement, caregiver support should be tailored to offer caring styles that adjust according to the caregiver circumstances and needs. Furthermore, assessing the psychological wellbeing of informal caregivers of individuals with dementia together with providing the necessary information on coping strategies that would support their caregiving role should form part of the dementia-management process.  The present research continues to add to the recommendations of the National Strategy for Dementia in the Malta in which the provision of holistic support services to community-dwelling individuals with dementia and their informal caregivers is one of the main priorities to be addressed (27).


Acknowledgements: The authors would like to thank the caregivers and individuals with dementia who participated in the study.

Conflict of interest: none

Funding: none

Ethical standards: Ethical approval for the study was granted by the Faculty of Social Wellbeing Ethics Committee and the Research Ethics Committee of the University of Malta.



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C. Scerri


Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta MSD 2080.

Corresponding Author: Charles Scerri Ph.D., Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida MSD 2080, Malta; Tel.: +356 23402905; Fax: +356 21320281; E-mail: charles.scerri@um.edu.mt

J Aging Res Clin Practice 2017;6:9-13

Published online November 3, 2016, http://dx.doi.org/10.14283/jarcp.2016.122



Abstract: Although a significant number of medical and pharmacy professionals come into contact with an increasing number of individuals with Alzheimer’s disease and other dementias, there is concern on the lack of knowledge and skills received during their undergraduate training programmes with the consequence of not providing the required hospital and community care for these individuals following programme completion. The aim of this report is to describe the results of a small scale study investigating the level of knowledge of Alzheimer’s disease and training needs in medical and pharmacy students at the end of their final year of undergraduate training. The findings indicated a lack of in-depth knowledge for both categories of students, in particular on risk factors and pharmacotherapeutic management highlighting an urgent need of refining existent training programmes that equip future medical and pharmacy professionals with the necessary skills in providing adequate care and management for individuals with the disease.

Key words: Alzheimer’s disease, dementia, medical students, pharmacy students, knowledge.



Alzheimer’s disease (AD) is the most common form of dementia accounting to 50-70% of all the cases (1). In 2015, it was estimated that 1.5% of the population in Malta had dementia, a figure that is projected to more than double in the next 30 years (2). This, in conjunction with the changing demographics favouring a progressive increase in the elderly population, will invariably put greater demands and challenges on medical and pharmacy professionals who, in the majority of cases, are at the forefront in providing formal care to these individuals both in hospital and the community. Concerns however exist that such healthcare professionals do not possess the required knowledge and skills to offer the required care and advice to these patients and their caregivers (3) with shortcomings in undergraduate curricula being one of the main reasons (4, 5). Such knowledge gaps were recently highlighted by general practitioners working in Malta as a motive towards their lack of understanding of dementia diagnosis and pharmacotherapeutic management of the cognitive and behavioural symptoms in individuals with dementia (6).
The aim of this study was to investigate the level of knowledge of AD, including its pharmacotherapeutic management, and training needs in final year medical and pharmacy undergraduate students.  The scope was to use the information gathered to support evidence on the need of enhancing dementia training in the current medical and pharmacy undergraduate curriculum in Malta with the latter being one of the priorites highlighted in the recent launch of the national dementia strategy (7).



The targeted population consisted of all full-time undergraduate medical (MD) and pharmacy (BPharm) students in the final year of their studies at the University of Malta, the latter being the sole higher education institution licensed to offer tertiary education in both medicine and pharmacy. The Maltese medical degree programme is a five-year university course organised by the Faculty of Medicine and Surgery. Dementia-specific topics are covered in teaching modules under the specialties of neurology, geriatric medicine, pharmacology and principles of good practice and psychological and social aspects of healthcare for a total of five hours throughout the whole training course. The Maltese undergraduate pharmacy 4-year programme is also organised by the Faculty of Medicine and Surgery with dementia training being delivered in a three-hour session focusing mainly on neuropathology, prevalence and pharmacotherapy.
The study consisted of a survey, in English language, composed of an anonymous closed-ended questionnaire and distributed to the students following the completion of all taught and clinical placement modules but prior to sitting for final assessment. The measurement tools included the Alzheimer’s Disease Knowledge Scale (ADKS) (8) and the Alzheimer’s Disease Pharmacotherapy Measure (ADPM). ADKS contains 30 true/false items aimed to assess knowledge on AD. It is designed to be used by healthcare professionals, students, patients, caregivers and laypeople to pinpoint educational needs (8). The questions focus on 7 subscales that characterise knowledge about AD namely on: risk factors, assessment and diagnosis, symptoms, course of the disease, life impact, caregiving, and treatment. The percentage correct score is calculated using the equation: sum of correct items/30 x 100. The ADPM was developed by the author. It consists of 18 true/false items focusing on knowledge about pharmacological management in AD including available treatment options, role of supplementation, drug efficacy, dose titration, adverse effects, augmentation therapy and the use of antipsychotics for the behavioural and psychological symptoms of dementia (BPSD). Face validity was ascertained by asking three local clinical medical specialists in the field of dementia to independently evaluate the relevance of the topics selected. Similar to ADKS, the percentage correct score for ADPM was found by calculating the percentage of dividing the number of correct items by the maximum possible score.
The survey also contained a section that requested participants to rate their educational and training needs using a 3-point Likert scale (ranging from 1: least, 2: moderately and, 3: most needed) from a list of 20 topics related to the care of individuals with AD and related dementias (9).
Background characteristics of participating students were collected via closed-ended questions that looked for information about age, gender, presence of and/or caring for a family member with dementia, and history of caring for persons with dementia during clinical placement. The study was approved by the Faculty of Medicine and Surgery Ethics Committee as well as the Research Ethics Committee of the University of Malta.
Descriptive statistics including mean data, standard deviations and percentages were used to describe socio-demographic data and the ADKS and ADPM scores. Following data analysis for normality of distribution by the Shapiro-Wilk test, the parametric independent sample t-test and the non-parametric Mann-Whitney U test were used for group comparisons. Mean data was expressed as mean ± SD (standard deviation). The significance level was set at 0.05. All statistical analyses were performed using PASW Statistics (Version 20).



A total of 82 medical (74.6% response rate) and 39 pharmacy (92.9% response rate) final year students replied to the questionnaire with the female gender being over represented in the pharmacy but not the medical programme. The majority of respondents indicated that they don’t have or care for a family member with dementia. Approximately half of the students in both programmes attended optional clinical placements with AD and related dementias patients (Table 1).

Table 1 Socio-demographic data, ADKS and ADPM scores of final year undergraduate medical and pharmacy students

Table 1
Socio-demographic data, ADKS and ADPM scores of final year undergraduate medical and pharmacy students

ADKS: Alzheimer’s Disease Knowledge Scale, ADPM: Alzheimer’s Disease Pharmacotherapy Measure, BPharm: pharmacy students, MD: medical students

Students who attended the medical programme had significantly higher percentage of correct ADKS scores compared to pharmacy students (t = 2.647, P = 0.009). Moreover, analysis of the ADKS subscales revealed that medical students were more knowledgeable in assessment and diagnosis (z-score = -2.987, p = 0.003) and risk factors (z-score = -3.712, p < 0.001) for AD. BPharm students who reported to have had exposure to dementia patients during their clinical placements had significantly higher scores in knowledge of risk factors (z-score = -2.041, p = 0.040), treatment and management (z-score = -2.194, p = 0.028) and symptoms (z-score = -2.091, p = 0.037) than their counterparts who did not have such exposure. A significant effect on the caregiving construct of the ADKS was reported in MD students having a family member with dementia (z-score = -2.241, p = 0.025) and in BPharm students caring for a family member with dementia (z-score = -2.036, p = 0.041). No significant differences were reported in the percentage correct ADPM scores between the two undergraduate training programmes (Table 1).
The mean scores in all educational and training needs topics were greater than 2 indicating that the majority of students in both undergraduate programme categories necessitate more knowledge in these subject areas. Compared to BPharm students, MD students expressed a greater need of having more training in recognising a patient with AD and related dementias and how to distinguish such medical conditions from others (z-score = -2.232, p = 0.026). Conversely, BPharm students scored significantly higher in educational and training needs involving the use of physical restraint and sedation (z-scores = -2.906, p = 0.004), the involvement of patients with dementia and their caregivers in decision taking on care and treatment (z-score = -2.514, p = 0.012), and how to promote interprofessional teamwork in managing patients with AD and related dementias (z-score = -3.004, p = 0.003) compared to their medical counterparts. The use of technology scored the lowest in both undergraduate training programmes whereas dealing with challenging behaviour scored the highest in BPharm students and second-highest in MD students (Table 2).

Table 2 Perceived educational and training needs of final year undergraduate medical and pharmacy students

Table 2
Perceived educational and training needs of final year undergraduate medical and pharmacy students

ADRD: Alzheimer’s disease and related dementias



The present study has shown that albeit the limited number of hours directed towards undergraduate dementia training, both final year medical and pharmacy students had adequate knowledge on AD with ADKS scores higher than US college students (8). However, analysis of ADKS subscales revealed that students following both undergraduate training programmes were unfamiliar with risk factors associated with the disease with a possible consequence of such students not being able to provide the required advice in terms of disease prevention upon graduation. Conversely, topics related to presenting symptoms and assessment and diagnosis were well recognised suggesting that they have the necessary skills to refer such patients to the appropriate support services for clinical assessment. However, whether such knowledge will eventually be translated into practice post-registration remains unclear. A recent national survey investigating practices in diagnosis, disclosure and pharmacotherapeutic management of dementia by general practitioners in Malta has found that referral to a dementia specialist was routinely adopted only by a limited number of practitioners (6). Interestingly, clinical placement played an important role in enhancing knowledge of risk factors, symptoms and treatment and management in pharmacy undergraduate students. It may be that learning through informal interaction with the care-recipient overcame any existing curriculum shortcomings and that hidden curricular activities can play a significant role in enhancing knowledge, shaping values and professional identity (10). A possible reason of why this has been observed in pharmacy and not medical students may lie in the different nature of their clinical placements. In MD students, these are mostly composed of ward rounds where students work in groups under the close guidance of medical specialists and with little hands-on experience. In addition, pharmacy students also attend pharmacy practice sessions designed to interact with clients on an individual basis thus enhancing the possibilty of building a closer relationship leading to a better understanding of their needs and concerns.  As previously reported with undergraduate nursing students (9), medical and pharmacy undergraduates who had or cared for a family member with dementia were found to have higher scores in the caregiving subscale of the ADKS.
Closer analysis of the ADPM scores revealed that, similar to what has been reported with general practitioners (6), the majority of final year medical and pharmacy students believed that early pharmacotherapeutic management of AD could postpone institutionalisation. This is expected due to the strong national emphasis that early management and diagnosis of AD could prevent dependency onto long-term services (7). Only a minority of students (36.6% MD; 47.8% BPharm) correctly indicated that AD pharmacotherapy does not stop the decline in activities of daily living. The observation that the lowest scores obtained for both undergraduate progammes (23.2% MD; 25.6% BPharm) was to a question related to the efficacy to acetylcholinesterase inhibitors was strongly indicative of the lack of in-depth knowledge of how these pharmacotherapeutic agents work. Questions related to drug management in challenging behaviour also yielded low scores possibly reflecting on the limited training that medical and pharmacy undergraduate students receive in this field during their study programmes. This is of particular concern due to an increase risk of mortality and morbidity following the use of antipsychotic drugs in managing BPSD (11).
Compared to their medical counterparts, pharmacy students significantly valued the need of enhancing training that promotes interprofessional teamwork in the management of patients with AD and related dementias. There is a strong case of incorporating interprofessional education interventions in undergraduate medical and pharmacy dementia curricula as this has the potential of improving knowledge related to dementia recognition and care (12, 13). Notwithstanding the recent  efforts by a number of national dementia plans together with individuals with dementia and their caregivers towards an increase in awareness and use of assistive technology (14), both medical and pharmacy students rated educational and training needs in this particular area as the least important. The lack of knowledge of how assitive technologies could support individuals with dementia may limit such healthcare professionals in providing advice on support systems that aim at enhancing autonomy, independence and quality of life.
In conclusion, this small scale study revealed that medical and pharmacy undergardaute training in the field of AD is not providing in-depth knoweldge and skills necessary to provide adequate care for these individuals. As a result, there is an urgent need to develop and implement pre-registration training modules designed to enhance the skills and better prepare the next generation medical and pharmacy professionals in the field of AD management and care.


Acknowledgements: The authors would like to thank the students who participated in the study.

Conflict of interest: none

Funding: none

Ethical Standards: Ethical approval for the study was granted by the Faculty of Medicine and Surgery Ethics Committee and the Research Ethics Committee of the University of Malta.



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D.A. Davey


Corresponding Author: Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Western Cape, South Africa 7925, e-mail profdad@eject.co.za, Tel +27 21 712 1314



Abstract: Alzheimer’s disease (AD) and cerebrovascular disease (CVD) frequently co-exist and CVD acts additionally and synergistically with AD in ageing–related impairment of cognitive function and dementia. A significant number of men and women with normal cognition at the time of death have the neurodegenerative and cerebrovascular changes of AD and CVD and are regarded as having high cognitive reserve or cognitive resilience. Many measures used to prevent and treat cardiovascular disease, decrease the incidence, or delay the onset of ageing-related cognitive impairment and dementia. Ageing-related cognitive impairment and dementia are increased by adverse psycho-social factors and can be prevented or mitigated by appropriate psycho-social measures. There is now more than sufficient evidence to implement, as a matter of urgency, personal health and life-style measures and public health initiatives in the endeavor to prevent, postpone or ameliorate ageing-related cognitive impairment and dementia and to decrease its burden world-wide.

Key words: Alzheimer’s disease, cognitive impairment, cerebrovascular disease, dementia, prevention.



Alois Alzheimer in 1906 described a “peculiar severe disease process of the cerebral cortex” with “miliary foci” (β-amyloid plaques) and “fibrils” (neurofibrillary tangles) in a patient with dementia praecox and the condition was named “Alzheimer’s Disease” (1). The term “Alzheimer’s Disease” is currently used in several different senses:
(a) specifically, by neurologists, psychiatrists and others to mean the form of neurodegeneration characterized by β-amyloid plaques and neurofibrillary tangles in the brain as described by Alzheimer. The term “vascular dementia” (VaD) is used for dementia attributed to cerebrovascular disease
(b) loosely, to include all forms of ageing-related cognitive impairment and dementia with varying cerebral pathologies
(c) generally, in non-medical circles instead of the word “dementia”.
The different uses of the term “Alzheimer’s Disease” have led to misunderstanding and the meaning may only be clear from the context. Alzheimer’s disease (AD) as first described by Alzheimer is but one of several causes of Ageing-Related Cognitive Impairment and Dementia (ARCID) (Table 1). The commonest are AD, cerebrovascular disease (CVD) and Lewy Body Disease (LBD) which frequently co-exist .It has been proposed that ARCID and dementia should be regarded as a syndrome i.e. a complex of symptoms with multiple causes, similar to other chronic diseases (2).
The purpose of this review is to substantiate the evidence that:
(A) AD and CVD are commonly associated and act additively and synergistically in ARCID
(B) Many risk factors for ARCID and measures that may prevent or postpone its development are very similar to the risk factors and measures to prevent and treat cardiovascular and cerebrovascular disease.
(C) Adverse psycho-social factors are significant risk factors for ARCID and psycho-social measures that increase cognitive reserve and resilience may prevent, delay the onset or ameliorate ARCID
(D) In the current absence of effective disease-modifying treatments, primary prevention combining all possible protective measures is the best hope to prevent, delay the onset and ameliorate ARCID


Association of Alzheimer’s disease and cerebrovascular disease

The cerebral pathology in men and women with dementia and of those with normal cognition at the time of death has been investigated in at least four major post-mortem studies: the Religious Orders Study and Rush Memory and Aging Project, the Medical Research Council Cognitive and Ageing Study, the Vienna Trans-Danube Aging Study, and The National Alzheimer’s Coordinating Centre USA Study (3-6). The main conclusions were very similar in all four studies, namely that the changes of AD and CVD (a) frequently co-exist in late-onset dementia (b) overlap to varying degrees and have additive and synergistic effects on cognitive decline (c) are sometimes found in persons with normal cognition at the time of death (7). The neurodegenerative and cerebrovascular changes associated with dementia form a spectrum from “pure” AD to “pure” CVD and most commonly are combined and result in “mixed dementia” (8) Fig1. The separation of AD as described by Alzheimer, and “vascular dementia” has been claimed to be a false dichotomy (8).

Table 1 Brain pathologies associated with cognitive impairment and dementia

Table 1
Brain pathologies associated with cognitive impairment and dementia

Figure 1 Conceptual Diagram of Mixed Dementia

Figure 1
Conceptual Diagram of Mixed Dementia


Cognitive reserve and cognitive resilience

A significant proportion of men and women with normal cognition at the time of death have the neurodegenerative and cerebrovascular changes of the brain associated with AD, CVD and dementia. The discordance between neuropathology and lack of cognitive impairment constitutes prima facie evidence for the role of some type of brain, neural or cognitive reserve (9). The absence of impaired cognition and dementia in such cases has been ascribed to high cognitive reserve and cognitive resilience. Cognitive reserve” implies high cognitive ability from early in life and its maintenance in mid and later life with the consequent prevention or postponement of ARCID (10). “Cognitive resilience” refers to the prevention or delay of ARCID in spite of the development of the pathological changes of AD, CVD and LBD.


Risk factors for ageing-related cognitive impairment and dementia

Ageing-related cognitive impairment and dementia has been associated with a large number of risk factors. A recent extensive meta-analysis of 323 papers including 93 factors considered suitable for epidemiological analysis, identified nine potentially modifiable risk factor; type-2 diabetes, obesity, hypertension, homocystinaemia, frailty, depression, current smoking, carotid artery narrowing, low educational achievement (11). The calculated population attributable risk combining all nine factors was 0.66 and it was claimed that two third of AD cases could be explained by these factors. In another study, potentially modifiable risk factors have been estimated to be present in approximately 50% of individuals with AD in the USA and worldwide (12). The seven modifiable risk factors included in these estimates were midlife hypertension, midlife obesity, diabetes mellitus, physical inactivity, smoking, depression and low education. The estimates do not take into account the non-independence of risk factors and the combined population-attributable risk factors have been estimated to be about 30% in the USA and Europe (13). Risk Factors can be divided into (a) Personal and Psycho-Social and (b) Cerebrovascular and Lifestyle (Table 2).

Table 2 Risk Factors for Ageing-related cognitive impairment and dementia

Table 2
Risk Factors for Ageing-related cognitive impairment and dementia


Personal factors

Personal factors including age, family history and the presence of the lipoprotein APOEε4 allele, are not modifiable but their effects can be mitigated or postponed by favourable environmental factors. Age is the most important factor determining the incidence and prevalence of cognitive impairment and dementia; the incidence of all-cause dementia increases exponentially from about 5/1,000 person-years in the 65-69 years age group to about 85/1,000 person-years in the age 90+ years (14). The most common genetic risk factor is the ε4 allele of the lipoprotein APOE4 and the APOEε4 allele has been estimated to increase the risk of AD about 3 times in heterozygotes and 15 times in homozygotes (15).

Psycho-social factors

Psycho-social factors often play an important part in ARCID and measures that increase cognitive reserve and cognitive resilience may be of considerable benefit in preventing, delaying or ameliorating ARCID. In an analysis of more than 20 studies involving 29,000 individuals followed for a median of 7.1 years, higher brain reserve was associated with a lower risk for incident dementia OR 0.54 (0.49–0.59) (10). The psycho-social factors that have been studied include, level of education, continuing cognitive activity and cognitive interventions, social and personality factors, depression and traumatic injury.

Level of education

The relative risks for low versus high education in a meta-analysis of 13 cohort and 6 case-control studies were, for AD 1.80 (1.43–2.27), for non-AD 1.32(0.92–1.88) and for all dementias 1.59(1.26–2.01) (16). In a meta-analysis of 31 studies with incident AD the pooled relative risk for lower education was RR 1.99(1.30–3.04)(17). In an analysis of 22 longitudinal studies including 21,456 individuals and 1,733 cases of dementia, the risk of dementia was lower for those with higher education OR 0.53 (0.45–0.62) (17). Low level of education is one of the biggest contributors to the high prevalence of AD world-wide (12).

Continued Cognitive Activity and Cognitive Interventions

A systematic review of 22 cohort studies including 29,000 individuals concluded that complex patterns of mental activity in early and mid-life was associated with a significant reduction in the incidence of dementia in later life RR 0.54(0.49–0.59) (10). In the Rush Memory Project frequent participation in cognitive stimulating activities was associated with less rapid decline in cognitive function and a lower incidence of AD, HR 0.58 (0.44–0.77) after controlling for a low baseline cognitive function, past cognitive activity, socioeconomic status and current social and physical activity (18). A Cochrane review in 2011 concluded that cognitive training interventions significantly improved immediate and delayed recall in healthy older adults and that more studies in other cognitive domains were necessary (19).

Social and Personality Factors

Social isolation and loneliness increase cognitive decline and the risk of late-life dementia (20, 21). Conscientiousness and purpose in life have been associated with a reduced risk of ARCID (22, 23). In the MRC-CFAS Study a combined Cognitive Lifestyle Score (CLS) based on educational attainment, occupational complexity and social engagement found that those who maintained a high CLS throughout life had a 40% reduced risk of developing dementia (24).


Depression may be a cause or consequence of cognitive impairment and dementia. A systematic review and meta-analysis of 20 studies including1,020,172 individuals found that history of depression increased risk of developing AD with a pooled OR of 2.03(1.73–2.38) for case control studies and of 1.90 (1.55–2.33) for cohort studies (25).

Traumatic brain Injury

Moderate and severe traumatic brain injury increases the risk of cognitive decline and is estimated to increase the risk of dementia in later life two to three fold (26). There is an increased risk of cognitive impairment and later onset of dementia in military veterans who have suffered brain injuries and in those involved in sports such as boxing and football of all forms, particularly in players who have experienced multiple concussions (27).

Cerebrovascular and life-style factors

Many cerebrovascular and lifestyle factors that predispose to ageing-related MCI and dementia are potentially preventable or modifiable (7). Measures that may prevent CVD are similar to those that prevent cardiovascular disease and include active treatment of hypertension, hyperlipidaemia and diabetes. The extensive study of 5,715 cases with a single neurodegenerative disease in the National Alzheimer’s Coordinating Centre USA database concluded that “in the absence of any specific disease-modifying treatments for Alzheimer’s disease in the near future, we urge, based on the high prevalence on cerebrovascular disease described in our data here, that aggressive management of vascular risk factors and encouragement of healthy life styles in mid-life may have benefit for Alzheimer’s disease or α-synucleinopathies individuals at increased risk to become clinically symptomatic, and probably to those with other causes of cognitive impairment. Indeed, even those who already manifest the clinical features of Alzheimer’s disease or α-synucleinopathy may benefit from effective therapies that mitigate vascular risk factors and cerebrovascular disease” (6).


Mid-life, but not late-life, hypertension is associated with an increased risk of AD and dementia with a calculated OR of 1.61(1.16–2.24) (28). A cohort of a random, population-based sample of 1449 individuals in Sweden was followed for an average of 21 years. Those with a raised systolic pressure in midlife (BP>160mm Hg) had a significantly higher risk of AD in later life OD 2.3 (1.0–5.5), after adjusting for age, body mass index, education, vascular effects, smoking and alcohol consumption (29). A quantitative meta-analysis of 14 studies of subjects without cognitive impairment or dementia, 32,658 with and 36,905 without hypertensive medication found no significant difference in the incidence of AD between the two groups but that those who had received anti-hypertensive medication has a significantly lower incidence of vascular dementia RR 0.67 (0.52–0.87) and of all-cause dementia RR 0.87 (0.7–-0.96) (30)


A systematic review of 18 prospective studies found a significant association between high mid-life total cholesterol (TC) and an increased risk of AD and all-cause dementia but there was only weak evidence of an association between TC and cognitive decline (31).


A number of systematic reviews and meta-analyses have reported an increased risk of impaired cognition or dementia in association with Type-II diabetes (11). A meta-analysis of prospective 28 observational studies found that the pooled relative risk of developing AD was 1.56 (1.41–1.73) of VaD was 2.27 (1.96–2.66) and all-cause dementia was 1.73 (1.65-1.82) (32). Diabetes increased the risk of conversion of mild cognitive impairment to dementia and Mediterranean diet decreased the risk (33).


In prospective studies and meta-analyses mid-life obesity has been found to be associated with a significant increase of all-cause dementia with a pooled estimate of RR of 1.60 (1.34–1.92) (17).
In addition to the specific effect of obesity on ARCID, obesity is associated with an increased incidence of hypertension, diabetes and cardiovascular disease.


A Mediterranean diet – high intake of vegetables, fruits, nuts and olive oil, relatively low intake of dairy products and red meat, and a moderate intake of wine – has been claimed in several observational studies to slow cognitive decline and to lower the risk of AD (34). In a prospective study of a similar “MIND” diet, high adherence was reported to be associated with a reduced risk of AD (35).


A review of 37 studies found that compared with never smokers, current smokers had an increased risk of AD (RR1.40 (1.13–1.73), VaD (RR 1.38 (1.15-1.66) and all cause dementia (RR1.30 (1.13-1.73) (36). The risk of all-cause dementia increased by 34% for every 20 cigarettes smoked per day but was not increased in former smokers. In a study of a cohort of 21,123 people, heavy smoking in mid-life was associated during two decades of follow-up with a more than 100% increase in AD, VaD and all–cause dementia (37).

Physical Inactivity

A review and meta-analysis of 16 prospective studies on the association between physical activity and dementia found that comparing highest v lowest activity groups the combined RR for AD was 0.55 (0.36–0.84) and for all-cause dementia was 0.72 (0.60–0.80) (38). These values have been reversed to reflect the risks with inactivity as 1.82 (1.19–2.78) for AD and 1.39 (1.6–1.67) for all cause dementia (12). A review and meta-analysis of physical activity in 21 prospective cohorts comparing higher with lower levels of activity the RR on cognitive decline was 0.65 (0.55–0.76) and on dementia was 0.86 (0.76–0.97) (39). A Cochrane analysis in 2015 found that healthy, sedentary elders who begin exercise have a significant improvement in cognitive function, particularly mental processing speed (40).


Prevention of ageing-related cognitive impaiment and dementia: Combined measures

In the absence of disease-modifying treatments, measures to prevent or postpone the onset of ARCID should include measures to prevent cerebrovascular disease and improve physical health and to ensure an optimum psycho-social environment. In view of the long preclinical phase of both CVD and AD these measures need to be actively instituted as early in life as possible and not later than mid-life. Many studies of individual risk factors have been published but there have to date been virtually no long-term, randomized, controlled studies of combined measures to prevent or postpone ARCID. A recent Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) reported the results of a double-blind, randomized, controlled trial of 2,654 individuals aged 60-77 years assigned in a 1:1 ratio to multidomain intervention (cognitive training, diet, exercise and vascular risk monitoring) or a control group (general health advice) (41). The primary outcome was a change in cognition in a neuro-psychological test battery score (NTB). The difference in NTB between the two groups after 2 years was statistically significant (p=0.03). There was also a significant difference in the secondary outcomes of executive functioning (p=0.04) and processing speed (0.04) but not in memory (p=0.36). It was concluded that a multidomain intervention can improve cognitive function in at-risk elderly people.



Nine population-based studies of dementia incidence and prevalence have reported a declining prevalence and age-specific incidence of dementia in England, Sweden, The Netherlands and the USA (42). The decreases have been attributed to rising levels of education, better prevention and treatment of cardiovascular disease and healthier life-style including exercise. It is uncertain whether these favourable trends will continue in the face of rising levels of obesity and diabetes in these populations, and whether they will manifest in low income countries. Although the age-specific incidence of dementia may be decreasing in some countries, the population of the world, the number living to advanced old age and the number with dementia world-wide is increasing. The incidence of dementia rises rapidly over the age of 75 and it has been estimated that the total number of people with dementia will triple from 2015 to 2050. The best hope for reducing the incidence and prevalence of ageing-related dementia currently lies in primary prevention, and in particular better education, continued mental and physical exercise and strict control of vascular risk factors. The evidence is now more than sufficient evidence to urge the immediate implementation of both personal health and life-style measures and public health initiatives to prevent or delay the onset of ARCID and to decrease the burden world-wide.


Acknowledgements: I wish to acknowledge the authors M. Valenzuela, M Esler, K Ritchie and H Brodaty (8) and the publishers Translational Psychiatry ©Macmillan Publishers Limited for permission to publish Fig 1.

Conflict of interest: There are no conflicting interests. I have received no funds or writing assistance in preparation of the paper.



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K. Kent1, S. Roodenrys2, K.E. Charlton1, R. Richards2, O. Morgan2, H. Gilbert2


1. School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Australia; 2. School of Psychology, Faulty of Social Sciences, University of Wollongong, Australia

Corresponding Author: K. Kent, School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Australia, e-mail:kc582@uowmail.edu.au



Background: Dietary flavonoid intake and intake of flavonoid subclasses has been associated with improved cognitive performance. However, the association between flavonoid intake and cognitive performance in older adults with Alzheimer’s type dementia has not been investigated. Objectives: To estimate dietary total flavonoid intake and intake of flavonoid subclasses in older adults with Alzheimer’s type dementia and assess the relationship of flavonoid intake with measures of cognition. Design: Cross sectional analysis. Setting: Community dwelling older adults in NSW, Australia. Participants: Older adults (+65y) with mild to moderate dementia (n=49). Measurements: A 24h diet recall was collected with help from a carer and used to estimate flavonoid intake. A battery of cognitive tasks assessed cognitive performance of several cognitive domains. Results: Pearson and spearman correlation coefficients identified an association between flavonoid intake and executive function (r=0.319, p=0.025). After controlling for depression, the relationship was reduced. Conclusion: The identified association between cognitive functioning, depression and flavonoid intake in older adults with Alzheimer’s type dementia warrants further research in a larger sample.

Key words: Flavonoid, cognition, dementia.



Flavonoids are naturally occurring plant-based phytochemicals, which are abundant in the human diet. The structure and sources of flavonoids has been well established (1, 2).  Flavonoids are a subclass of polyphenols and encompass a wide group of compounds that are divided into six major classes: anthocyanidins, flavanols, flavanones, flavones, flavonols and isoflavones (1). A growing body of evidence suggests that flavonoids are non-nutritive bioactive compounds, which significantly contribute to the antioxidant activity of individual fruits and vegetables and are consequently credited with the observed health benefits (3). Flavonoids are widespread across many food sources and are found in particularly high concentrations in fruits and vegetables, wine, tea, cocoa, and soy (4). In older Australian adults, major dietary sources of flavan-3-ols and flavonols are tea (black and green) and apples; flavanones are provided by citrus fruits and juices; flavones are consumed through parsley and tomatoes; and berries and red wine provide anthocyanins (5). Isoflavones are largely provided by the consumption of soy-based products (6).
Total dietary flavonoid consumption has been association with improved cognitive performance and a preservation of cognitive function with ageing (7-9). More focussed research on specific flavonoid subclasses has revealed that the sub-groups flavanols, anthocyanins and flavanones may provide the most beneficial effects in the area of neuroprotection (10). There has been a particular focus in animal models, on the provision of anthocyanin rich foods, such as blueberries, when investigating cognitive outcomes, with promising results (11-13). Preliminary human trials have also begun to link anthocyanin-rich food consumption with improvements in cognitive outcomes (14-18).  A high consumption of total dietary flavonoids has also been linked with a reduced risk of developing a neurodegenerative disease, such as dementia (19). However, the association between flavonoid intake and cognitive performance in older adults with Alzheimer’s type dementia has not been investigated to date.
The mechanisms by which flavonoids provide neuroprotection are not well elucidated and the evidence remains largely pre-clinical. This is partially related to the quick and extensive metabolism of dietary flavonoids into metabolites with differing and largely unknown biological activities (1). In animal models, specific flavonoids including the flavanols catechin and epigallocatechin gallate (20) have been shown to reduce neuroinflammation and scavenge free radicals within the brain (2), a function which has been related to neuroprotection. Additionally, flavonoids, including the flavanone hesperitin have been shown to provide a range of positive neuronal effects to limit neurodegeneration, including a potential to protect neurons against injury and improve neuronal morphology (2, 21). Flavonoid supplementation has also been shown to up-regulate processes that promote learning, memory and cognition (1). Flavonol-rich cocoa consumption has shown to increase cerebrovascular blood flow, which is associated with improved cognition (22). Presently, it is unclear how many, or if all flavonoids exert such effects (1).
Evidence is mounting for the positive protective effects of flavonoid consumption for the development of dementia (7, 19, 23), including consumption of flavonoid rich fruits and vegetables, juices and wine (24, 25). However, it is also important to investigate the relationship between flavonoid consumption in older adults living with dementia and cognitive performance outcomes. This evidence could be utilized to indicate if dietary interventions with flavonoids may be warranted. It is well documented that older adults with dementia develop eating difficulties, resulting in low food intake, as dementia progresses (26). This can be related to a myriad of difficulties including dysphasia, lack of appetite, confusion about the need to eat and the loss of the ability to recognize food (27). The total dietary intake and significant sources of dietary flavonoids in older adults living with dementia has not been assessed and may differ from estimations for healthy adults aged 65+yrs.
The aim of this study was to estimate the total dietary intake and main sources of flavonoids in older Australian adults with Alzheimer’s type dementia and to assess the relationship between dietary flavonoid intake and cognitive performance.



This study was approved by the University of Wollongong and Illawarra Shoalhaven Local Health District Human Research Ethics Committee (HE11/175) and complied with current laws governing ethics in research. The current study analysed the baseline data of a randomised controlled trial, which investigated the impact of anthocyanin-rich cherry juice on cognitive outcomes in older adults with dementia (17)
Community dwelling older adults (65+yrs) with mild to moderate Alzheimer’s type dementia (as diagnosed by a hospital-based geriatrician) were recruited to the study from an outpatient clinic. Dietary data was collected by a trained nutritionist (KK) (with assistance and confirmation provided from a carer) from a single 24-h food recall. The dietary data was analysed using the Foodworks dietary analysis package (Xyris software, version 5, 2007, Highgate Hill, QLD, Australia) (28). As dietary data relating to flavonoid content of foods is not integrated into the Xyris software, the food items were manually cross-referenced with the USDA database for the flavonoid content of selected foods (release 3.1) (29) to estimate total flavonoid consumption and the flavonoid subclasses anthocyanins, flavones, flavanones, flavonols and flavan-3-ols. A Mini Nutritional Assessment (30) was conducted as a measure of malnutrition and Lawton’s Instrumental Activities of Daily Living Scale (31) measured functional ability. Anthropometric and demographic information, including education, was collected (Table 1), with assistance from a guardian or carer as appropriate.

Table 1 Characteristics of study participants (n=49)

Table 1
Characteristics of study participants (n=49)

Ideal BMI for adults 65y+ is 22–27 kg/m2 (13); Calf circumference and mean mid-upper arm circumference in of 29.2 in older adults; Mini Nutritional Assessment score >23.5 indicates no risk of malnutrition (14); Median maximum hand grip strength are 37.9 kg and 31.5 kg for men and women aged 50y+ (15); Lawton’s IADL scale mean score 4.3 in adults with moderate dementia (11).


A battery of cognitive assessments was administered by a single trained researcher (KK). These included measures of mood (32), verbal learning and memory (33), working memory (34), semantic memory (35), executive function (36, 37) and short-term memory (38) (Table 2).


Table 2 Cognitive instruments, domain targeted and relationship with total flavonoid intake

Table 2
Cognitive instruments, domain targeted and relationship with total flavonoid intake


Correlation is sig. at p<0.05. ** Correlation is sig. at p<0.01


To assess the relationship between flavonoid intake and cognitive performance, bivariate correlations with Pearson and Spearman coefficients (as appropriate) were performed and then repeated after controlling for depression, as measured by the Geriatric Depression Scale (GDS) (32). Multiple regression analysis was performed to confirm the effect of flavonoid intake on cognitive outcomes that were identified as significant by the correlations, with age and education included in the models as covariates.



Forty-nine participants volunteered to take part in the study; their anthropometric and demographic characteristics are found in Table 1.

Figure 1 Percentage contribution of flavonoid subclasses to total flavonoid intake

Figure 1
Percentage contribution of flavonoid subclasses to total flavonoid intake


Analysis of the 24h dietary recall calculated total flavonoid intake to be 510.2 ± 374.8mg/day, with a range of 5.9 – 1,524.2 mg/day. Black tea contributed 80% of total dietary intake and was the most notable dietary source of flavonoids. Other notable sources were green tea (7.5%), red wine (4.5%), with apples and oranges providing 1.7% and 1.6% respectively, when combined with their fruit juices. The dominant subclass of flavonoids was flavan-3-ols; these contributed 88% of total intake (Figure 1).

Total flavonoid intake was not significantly correlated with age, nutritional status or education. However, participants who displayed greater depressive symptoms (i.e. scored higher on the GDS) had a lower total flavonoid intake (r=-0.328 p=0.021).
Total flavonoid intake was significantly correlated with verbal fluency (r=0.319 p=0.025) (Table 2). Verbal fluency was also significantly correlated with the flavonoid subclasses flavonols (r=0.321 p=0.025), flavan-3-ols (r=0.323 p=0.023) and anthocyanins (r=0.298, p=0.038). No other significant associations were identified. A regression analysis was conducted to predict verbal fluency from total flavonoid intake, with age and education as covariates. Total flavonoid intake statistically significantly predicted verbal fluency score (β =0.319, p=0.025) controlling for age (β=0.042, p=0.765) and education (β=0.219, p=0.124). The overall model fit was r2=0.148.
After controlling for depression (GDS continuous score), bivariate correlations showed no significant relationship between total flavonoid intake or flavonoid subclasses was shown (Table 2).



The mean intake of total flavonoids (510mg/day) in this sample of older adults with mild to moderate Alzheimer’s type dementia is lower than the other estimations in older Australian adults, which were 683mg/day (5) (from 12 day food records) and 575mg/day (from a single 24h dietary recall) (39). However, the major dietary sources and percentage contributions from each flavonoid subclass are similar (5, 39). Black tea was the major dietary source of flavonoids (80%), and this finding highlights a limited fruit and vegetable consumption in this group.
The relationship between cognitive performance on the verbal fluency task (a measure of executive function), and flavonoid intake is supported by literature which suggests that executive function can be positively influenced by flavonoid supplementation and habitual flavonoid intake (40). The relationship between verbal fluency and intake of the flavonoid subclasses flavonols, flavan-3-ols and anthocyanins (but not flavanones, or flavones) may be related to the consumption of  black and green tea (the major sources of flavonols and flavan-3-ols) and berries (a major source of anthocyanins), in this group. The consumption of both green and black tea has been associated with improved cognition in older adults (41), although a recent systematic review considered the role of tea in mild-cognitive impairment and dementia progression and reported that the findings were too limited to draw conclusions (42).  Similarly, the consumption of anthocyanin rich strawberries and blueberries has been associated slower cognitive decline (43).
The lack of correlation between total flavonoid intake and education, nutritional status and age indicates that in this cohort these factors do not impact on total flavonoid consumption. This may be explained by tea consumption, the largest contributor to total flavonoid intake being a universally consumed item by all socioeconomic groups, and also reflects the lack of energy or micronutrients provided by this beverage, thus not impacting on nutritional status.
The positive association between depressive symptomatology (as measured by GDS) and flavonoid intake (r=-0.367, p=0.009) is interesting. The reduction in association between verbal fluency and flavonoid intake when depression was included as a covariate suggests that this relationship is confounded by the effect of depression on executive functioning. We speculate that epidemiological studies that have reported associations between flavonoid intake and cognitive outcomes, without controlling for depression, may have overestimated the strength of this relationship (7).
There is little consensus regarding which cognitive domain is impacted by flavonoid intake (40, 44) or which tool should be employed to measure this effect (44). We therefore used a battery of cognitive tests in order to investigate a wide range of domains of cognitive function, ensuring that each of the validated tests was sensitive and specific. Generalizability of the study findings is limited by the small sample size and the non representative nature of the convenience study sample. Other limitations include the inadequacy of using a single 24h dietary recall to estimate habitual dietary flavonoid intake. Aside from the limitations associated with this dietary assessment method, there are several well documented problems associated with utilising food composition databases to assign flavonoid content to selected foods to reflect dietary intake. These limitations include an incomplete list of flavonoid containing foods, non-regional specific data (there is no Australian database for the flavonoid content of foods comprising the Australian food supply), and the inability of a dietary assessment to account for the high intra-individual variation of flavonoid absorption and metabolism (45). These limitations may result large variations in estimations of flavonoid intake (6) that differ from the true value, and may hinder our interpretation of observational data that associates flavonoid intake with specific health outcomes.
In conclusion, dietary intake of flavonoids in a sample of older adults with Alzheimer’s disease was found to be somewhat lower than current Australian estimations for this age group, but the contributions of dietary sources are similar to the general older population. The identified association between cognitive functioning, depression and flavonoid intake in older adults with Alzheimer’s type dementia warrants further research in a larger sample to confirm the findings and to identify whether dietary interventions may be indicated.


Funding: This study was conducted with funding from the Illawarra Health and Medical Research Institute. The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; in the preparation of the manuscript; or in the review or approval of the manuscript.

Acknowledgements: None

Conflict of interest: None

Ethical standards: This study was approved by the University of Wollongong and Illawarra Shoalhaven Local Health District Human Research Ethics Committee (HE11/175) and complied with current laws governing ethics in research.



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J.G. Anderson, K.M. Rose, A.G. Taylor


Virginia, Charlottesville, Virginia, USA

Corresponding Author: Joel G. Anderson, PhD, CHTP, Department of Acute and Specialty Care, University of Virginia School of Nursing, P.O. Box 800782, Charlottesville, VA 22908-0782, Telephone: (434) 243-9936, Fax: (434) 243-9938, Email: jga3s@virginia.edu



Objective: Family caregivers are the mainstay of caregiving support to persons with dementia, and often care for a family member with dementia for a decade or more prior to institutionalization or death. Malnutrition, including weight loss, is common among older adults with dementia, occurs throughout the disease process, and is associated with institutionalization and death. Nutrition education for caregivers is an important aspect of addressing the care needs of adults with dementia; however, nutrition education research in community-based persons and families experiencing dementia is minimal to non-existent. The need for tailored education resources ranks as highly important among caregivers; however, the nutrition concerns of caregivers in the home have not been identified. The purpose of the current study was to gather descriptive data about the nutrition-related concerns of family caregivers of persons with dementia. Design: A qualitative descriptive design using semi-structured interviews of caregivers of persons with dementia (n = 4) was used to collect the data. Thematic and content analysis was used. Results: Family caregivers experienced nutrition-related concerns and described a need for nutrition education to support the caregiving role. Four themes emerged: (1) meal preparation and food choices; (2) lack of appetite and eating behaviors; (3) making sense of existing nutrition information; (4) searching for reliable nutrition information. A discussion of each theme, including exemplars, is presented, along with suggestions provided by participants regarding how to address existing nutrition education resource needs.Conclusions: Issues surrounding care often are complex and require accurate and tailored information. Findings from the current study provide rich, valuable data regarding the needs of family caregivers with respect to nutrition concerns, allowing for the development, design, testing, and delivery of nutrition education resources and strategies.

Key words: Dementia, caregiving, nutrition education, eating behaviors.



Over the past 50 years, the understanding of the impact of nutrition and dietary patterns on health has become increasingly important (1), facilitating a growing interest in the relationships between aging, nutrition, and cognition among both the public and researchers (2). Weight loss and malnutrition are common issues among older adults with dementia (3-6), occurring throughout the disease process and associated with death, muscle loss, loss of independence, and institutionalization (5, 7). Additionally, insufficient caloric intake is associated with reduced cognitive function, sleep disturbances, and fatigue (8, 9). Impaired nutritional status is associated with the severity of dementia, particularly the behavioral and psychological symptoms expressed by persons with dementia (10).
Providing care for a family member with dementia is recognized as a chronically stressful situation that may have a negative impact on the mental and physical health of the caregiver (11). Being a caregiver is not only linked with high levels of burden, depression, and anxiety (12), but also has a potentially negative impact on the nutritional status of the caregiver (11). Nearly a quarter (21%) of family caregivers of persons with dementia are at risk for malnutrition (13), and those with depressive symptoms are more likely to present with a poor nutrition status. Additionally, the nutritional status of the family member with dementia is inversely associated with the level of burden experienced by the caregiver (14).
The specific nutrition concerns and issues of caregivers in the home in the United States have not been identified. Given this fact, whether or not existing nutrition education resources adequately and accurately address the nutrition concerns of caregivers also is unknown. Studies are needed that identify topics and themes for potential interventions specific to caregiver needs and types, that incorporate data collection at sites convenient to the caregivers, and that are oriented toward maintenance or improvement of dietary habits during the caregiving process to decrease the risk of chronic disease and reduce caregiver burden (15). Thus, the aim of the current study was to identify the nutrition-related concerns and topics important to informal caregivers of persons with dementia.



Study Sample

Participants were recruited using study flyers placed in aging care clinics, assisted living facilities, inpatient clinical areas, and Web advertisements. Eligibility criteria of potential participants included individuals who (a) self-identified as an unpaid, informal caregiver for a person with a physician-confirmed chronic, dementing illness per standard neurological criteria for dementia, (b) were 18 years of age or older, (c) were able to speak and understand English, and (d) were willing to engage in a 30-45 minute semi-structured interview. All aspects of the study were approved by the Institutional Review Board for Health Sciences Research.

Interview Procedure

Demographic information including age, marital/partner status, education, ethnicity and race, income, employment status, and number of months in the caregiving role of the caregivers was obtained. A semi-structured interview, lasting approximately 45 minutes, was conducted using an interview guide and prompts adapted from Keller et al. (5) (Table 1). Questions focused on nutrition and eating issues of both the care recipient and the caregiver. Interviews were conducted either in person or via telephone. Detailed notes were taken in addition to audio recordings; these recordings were transcribed in full for qualitative analysis.

Data Analysis

Transcripts from the interviews were analyzed separately and in aggregate to gain the unique perspective of each interview and the overall results. Data from the interviews were organized, analyzed, and interpreted using content analysis (16) and supplemented by a thematic analysis approach (17). Dedoose software was used for the data analysis, and codes were ascribed. The lead author (JGA) used the analysis steps delineated by Weber: review the narratives, define coding units, define categories, test coding, assess accuracy or reliability, and revise the coding rules and assess the accuracy (16). Codes were created based on the verbatim words used by the participants in the interview. Definitions for codes were described in a coding manual to help the research team remember the exact meanings of the existing codes whenever a new code was created. Memos included expression of thoughts in words, sentences, diagrams, and symbols. The maintenance of analytic memos throughout the data analysis process helped research team members to identify the categories and themes as these emerged from the analysis.
Transcripts were analyzed multiple times in different orders and also simultaneously after the initial analysis to ensure that no codes were missed. The research team met and compared the data analysis results, including the emerging codes and categories. Coding was initially completed by the lead author and categories developed. Other members of the research team were asked to review the narratives independently and review the categories. Research team members maintained memos to draft both thought processes and their own individual assumptions and biases. The codes were then organized into a broader classification of categories. The groups of codes that expressed the same ideas or phenomena were classified broadly into categories. Major themes evolved that subsumed all of the categories, the defining properties, and the interrelationships. The research team discussed findings and reached consensus surrounding the themes that emerged from the data.  



The sample (N = 4) consisted of Caucasian caregivers ranging in age from 27 to 83 years. Two caregivers were the children of a person with dementia, one was a grandchild, and one was a spouse. The amount of time spent in the caregiving role ranged from 10 months to 10 years. Three caregivers lived with their care recipients while one provided care to a family member who resided in an assisted living facility. Family caregivers experienced nutrition-related concerns and described a need for nutrition education to support them in the caregiving role. Four overall themes emerged from the analysis: (1) meal preparation and food choices, (2) lack of appetite and eating behaviors, (3) making sense of existing nutrition information, and (4) searching for reliable nutrition information.

Meal preparation and food choices  

Caregivers expressed concerns and issues related to the preparation of meals in the home, as well as food selection and food choices in the home, outside the home and, in one instance, assisted living facilities, which were described as “not so much focused on fresh fruits and vegetables.” Participants related instances in which meal preparation and food choices led to experiences of stress and burden, as in the following exemplar:
“…there’s this big stress about, ‘Oh, what are we going to eat now.’ And then it’s like, ‘Oh, we have to go the store for it.’ It’s not like…any sort of planned meals ahead of time. It’s always like, «Okay, it’s 12:00. We have to eat something. Let’s go to fast food or something like that,» which…isn’t…great obviously.”
Additionally, because all of the caregivers were interested in providing their loved ones with nutritious food choices and options, this desire increased the stress and burden experienced by the caregivers. One participant stated:
“You’ve got to fix the meals for her…I don’t go out and buy food at a restaurant cause [sic] I don’t know what they’re putting in it and I want to give her the healthiest options I can. So when I’m taking the food, I have to go do the shopping and then the preparation and then I take it over and then eat with her. So it’s a much more involved process.”
Caregivers also experienced stress when trying to engage a care recipient who at one time was the primary meal preparer for the family. Learning to step in the role and be more actively involved in meal preparation was a source of angst. One participant related the following:
 “…one of the things that the women in my family prided themselves on was being good cooks. You know Southern cooking. It’s…nurturing. It’s…comforting. So at the early stages you know we still tried to say, ‘hey, why don’t you cook this?’ And we would be kind of glancing to make sure that everything…was okay. But…[she] can’t do that now.”

Lack of appetite and eating behaviors

Caregivers spoke of issues related to feeding challenges, the most common being a lack of appetite. For instance, one participant stated that her family member with dementia was “…willing to eat what I put in front of her but there’s…no active participation. She’s not seeking anything.” Participants described their care recipients as “distracted” at meal times. For example, one participant stated “I will prepare a meal that I think is nutritious but…[she] doesn’t have the ability to sit still that long.” Another noted “…we’ll sit there for 10 [or] 15 minutes and then she’ll want to get up.”
With regard to a perceived lack of appetite, caregivers were frustrated by not knowing whether or not their loved one with dementia was simply not hungry or was unaware of their need or desire to eat. One participant stated “…she doesn’t seem to be aware of whether or not she’s hungry and she also doesn’t take it upon herself to eat.” Another said “…if you ask her if she’s hungry, she’ll ask someone else if they’re hungry.” This situation was described as “complex,” with one participant stating “…I don’t think [she] forgets to eat. But she does have to be prompted to eat.”
These eating behaviors were a source of frustration for caregivers, who were unsure how to approach these issues to provide quality care for their loved one. One caregiver expressed their frustration saying, “…sometimes she says she’s not hungry and…I know she hasn’t eaten since the morning and it’s like 5:00 [in the evening] or something.” Caregivers were uncertain if they “should be sort of saying, ‘Have you had three meals each day?’” or allow their care recipients to regulate meal times on their own. The level of uncertainty, frustration, and lack of knowledge related to whether or not their loved ones were capable of recognizing hunger is expressed in the following exemplar:
“[What is]…the best way to sort of handle that, whether or not it’s okay to just say, ‘Well, you need to eat something,’ or to actually listen to her when she says she’s not hungry,”
Caregivers also expressed concerns about their own health when dealing with erratic meal times, lack of appetite, and problematic eating behaviors that they experienced while caring for a family member with dementia, as depicted in the following:
“And also there’s the appetite problem,…she doesn’t want to eat and so in order to get her to eat, you have to eat with her. So, that’s a problem for me because I don’t eat that much. And when I do eat that much I gain weight and she wants me to be there eating the meals in the facility with her. And there is…nothing that they serve that I want to eat. But I’ve got to eat what she’s eating…she even compares amounts. Like you’re not eating as much as I’m eating.”

Making sense of existing nutrition information

Caregivers were very much interested in accessing and making use of nutritional information. This desire was fuelled by the question expressed by each of them–“what should I really be doing?” However, the participants expressed difficulty not only in finding information, but also making sense of the information that they located, as in the following example:
“…I don’t really ever get great answers. I sort of get mired in…what’s going on or where’s the reputable resource or where’s…the current…information…It would be nice to know…that I could go to the Alzheimer’s Association Web site and see…the general idea or consensus on a topic.”
Additionally, caregivers were frustrated by a lack of synthesis regarding existing nutrition information and resources, as well as the response by health care professionals to their requests for more information, as expressed in the following:
“I think there is just such a body of knowledge that it’s hard, nobody’s been able to…really synthesize what’s going on out there and new stuff keeps hitting the airways and so everybody is trying to digest it. And the answer of the health care provider seems to be a pill. And that has never been a favorite of mine. If you don’t have anything else for me,…I don’t have a lot of confidence in you as a health care provider if all you have to offer me is a pill.”

Searching for reliable nutrition information

The desire to locate and use reliable nutrition information and resources was expressed by each of the caregivers. The impetus of this search was most often led by the participants’ own interests in nutrition and providing nutritious, healthy food choices and meals that would enhance the health of their loved ones, potentially slowing the progression of the disease. One caregiver stated,
“I want to feed her and have her eat as healthy a diet as possible…if there was a way that I felt was possible to manipulate the diet to slow the [mental] decline, I would be interested in that. Or even to make her…clearer thinking, regardless of what level she’s at. Those are the kinds of things I’m interested in.”
Frequently, caregivers spoke of searching for resources that were “backed up by people who are experts in the field who should actually be able to interpret the results correctly of research studies.” One caregiver stated, “I wish that there was something that I felt confident was…evidence-based.”
In their efforts to uncover the sought after nutrition information and resources, caregivers described challenges in finding the information for which they were looking. One stated, “…I don’t think I ever find like, ‘oh, this is exactly what I was looking for. And this is the answer.’ I think I spend a lot of time looking.” Another caregiver expressed the following:
“I tend to find it difficult to find reputable sources…when you’re just looking on the Internet, there’s no clear indication that this is a worthwhile resource or…whether this study was…disproved like a month later or something.”
The level of frustration can be best summed up by one caregiver who said, “…I haven’t found anything…because I’m looking for the answer and nobody has the answer.”


Table 1 Interview questions and prompts



In the current study the researchers identified four themes related to the nutrition concerns and issues experienced by caregivers of persons with dementia: (1) meal preparation and food choices, (2) lack of appetite and eating behaviors, (3) making sense of existing nutrition information, and (4) searching for reliable nutrition information. To the authors’ knowledge, this is the first study to explore the nutrition-related concerns of the family caregivers of community dwelling adults with dementia conducted in the United States. The findings of the present study point to a need for tailored, evidence-based nutrition education resources for the family caregivers of persons with dementia.
As family members with dementia experience a continued loss of autonomy and cognitive decline, caregivers must deal with an increasing array of challenges, including those involved in managing the diet and food preparation of their loved one (18). Caregivers in the current study described modifications and concerns related to meal preparation and food choices. In previous studies, caregivers have listed changes in the food preferences, as well as the loss of autonomy in meal preparation and food choices, as the main dietary challenges involved in caring for a family member with dementia (19-23). As the disease progresses, this loss of autonomy, as well as difficulties related to feeding, may lead to a poorer nutrition status for the person with dementia (19).
Informal family caregivers often have limited knowledge about the behavioral and psychological symptoms expressed by persons with dementia and may have difficulty interpreting behaviors, especially during mealtime (24). For example, Alzheimer’s disease is typically associated with changes in episodic memory, including an inability on the part of the person with dementia to recall whether or not s/he has eaten. Caregivers in previous studies identified decreased food intake and a lack of appetite as dietary challenges experienced while caring for a family member with dementia (19-23). This decreased food intake concomitant with progression of the disease may result from poor appetite, as well as depressed mood (23). Over time, inadequate food can lead to malnutrition, weight loss, and increased risk of mortality (7).
Apathy is a behavioral and psychological symptom of dementia that has been shown to be particularly burdensome for caregivers (25). Apathy on the part of the person with dementia often leads to a lack of participation in activities of daily living, including mealtimes and eating, and may require more intensive stimulation and engagement from the family caregiver (14). Apathy could weaken emotional and social exchanges between the caregiver and care recipient during mealtimes, decreasing the psychosocial function of eating with others (26). This is important given than mealtime quality recognized as essential factor to improve nutritional status of persons with dementia (27).
Family caregivers have been shown to possess poor nutrition knowledge and to be able only to recognize signs of gross malnutrition in the care recipient (28). Participants taking part in a study examining a caregiver education intervention scored lower on pre-tests for modules related to nutrition (29). Thus, nutrition education of caregivers is a potentially important aspect of addressing the care needs of adults with dementia. However, nutrition education research in persons and families experiencing dementia in the community is scarce, with caregiver education most often focused on the disease process of AD and dementia or general issues associated with the care recipient (5). Thus, family caregivers have been neglected in nutrition research, policy, and practice (15). Caregivers may benefit from nutrition education by enhancing their ability to provide nutritionally adequate diets for their care recipients, as well as helping them maintain their own health and well-being (15). Nutrition-related chronic diseases associated with aging and that increase risk of AD, including CVD, diabetes, pulmonary disease, and cancer, occur in up to 86% of adults ≥70 years of age (15). This is significant given that more than 30% of caregivers for the elderly are, themselves, age 65 years or older (30).
Many caregivers have cited a critical need for information (31) and identified educational support to be of more importance than additional task-oriented assistance (32). The need for tailored education resources ranks as highly important among caregivers, particularly in rural communities (31-36). Caregivers in international studies have indicated the need for nutrition education information specifically. In a Japanese survey study, Hirakawa and colleagues (37) found that almost 50% of respondents were interested in specific and tailored food and nutrition information, finding that an overabundance of such information can be overwhelming and complicate the care process. In a Swedish study (6), spousal caregivers expressed concerns about how they struggled “to be a good food provider in everyday life” as a result of changing food preparation roles and coping with becoming a caregiver. The participants expressed concerns of gaps between available nutrition education resources and the quality of information presented (6).
The most common sources of information for family caregivers of individuals with AD and dementia include the Alzheimer’s Association, allied healthcare professionals, family members, friends, clergy, and support groups (35). A previous study by Keller and colleagues (5) evaluating printed nutrition education resources provided by dementia society chapters found the need for development of better resources. In a recent study, half of the caregivers in the sample expressed interest in engaging in a nutrition education program (23). These same caregivers provided potential motivators for encouraging caregivers to take part in nutrition education programs, including the ability to feed and care adequately for a loved one with dementia, to learn more about nutrition, and to provide motivation for caregivers themselves to improve their eating habits (23).
Limitations of this study relate to the small sample size, which limits generalizability. However, while there were only four participants in the current study, saturation was reached with regard to the primary research question. Moreover, theoretical saturation in similar studies was achieved generally within in six interviews (38).
Issues surrounding care often are complex and require accurate and tailored information. By collecting descriptive data about caregiver needs, assessing current nutrition education resources, and critically examining the current evidence base, themes, and knowledge gaps can be identified. This study took a holistic approach to evaluating the problem and the findings provide information for future studies aimed at designing, testing, and disseminating new nutrition education materials tailored specifically to caregiver needs that address existing gaps in education resources while providing the most currently available evidence-based knowledge and dietary recommendations.


Conflict of interest: The authors have no conflicts of interest..

Ethical standard: The study was approved by the university’s Institutional Review Board.



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N. Cano-Cuenca1,2, J. Solís-García del Pozo1,3, J. Jordán1,4

1. Departamento de Ciencias Médicas. Facultad de Medicina de Albacete. Universidad de Castilla-La Mancha (UCLM). Spain; 2. Servicio de Farmacia. Hospital de Hellín. Spain; 3. Servicio de Medicina Interna. Hospital General de Villarrobledo. Spain; 4. Grupo de Neurofarmacología. Instituto de Investigación en Discapacidades Neurológicas-UCLM. Spain.

Corresponding Author: Joaquín Jordán, Grupo Neurofarmacología. Departamento de Ciencias Médicas. Facultad de Medicina de Albacete. Universidad de Castilla-La Mancha. Calle Almansa, 14. Albacete-02008. Spain. Telephone. +34-967599200. Fax+34-967599327. e-mail: joaquin.jordan@uclm.es



Background: Citicoline is considered an ingredient in particular foods in the USA and is available in pharmaceutical form in Europe and Japan. It has been postulated to render positive effects on the nervous system, either by increasing levels of neurotransmitters, or by affording neuroprotection. Methods: Several clinical trials have shown the efficacy and safety of this biomolecule in several neurodegenerative diseases and in acute ischemic stroke. Here, we have performed a systematic review to validate the effect of citicoline on MMSE, memory, attention, and basic activity of daily living. In electronic database searches, we found 14 randomized clinical trials reporting citicoline effects on cognitive function. Findings: A positive effect of citicoline on MMSE in acute ischemic stroke was found, which was not evidenced for Alzheimer disease or vascular dementia. On activities of daily living, citicoline failed to exert beneficial effects in patients with acute ischemic stroke or progressive cognitive impairment. Conclusions: Given the present data there is no evidence that supports advising patients with cognitive alterations to take chronic citicoline supplements. 

Key words: CDP-choline, cytidine, Alzheimer disease, dementia, cognition, meta-analysis, acute ischemic stroke. 



Besides being the central symptom of dementia, cognitive impairment is the principal cause of a wide range of disabilities affecting attention, mnesic, linguistic and visuo-spatial abilities (1). Alterations in cognitive functions are present in neurodegenerative diseases, including cerebrovascular disorders such a stroke or vascular dementia (2). Among the pharmacological arsenal tested in stroke is the biomolecule Citicoline (CDP-choline or cytidine-5´-diphosphocholine) (3). Although its mode of action is far from being clarified, evidence supports citicoline roles in cellular pathways related with neural cell death prevention. Thus, citicoline increases levels of neurotransmitters, including noradrenaline, dopamine and serotonin (4). Furthermore, citicoline might enhance tolerance to ischemic brain damage by preventing cell membrane damage and impaired phospholipid metabolism described during stroke (5). Preclinical evidence supports citicoline providing efficacy and optimal neuroprotective profile in stroke animal models (6, 7).

This neuroprotective role leaded the clinician to perform clinical trials aimed to ascertain the efficacy of citicoline on stroke [8-13] and other neurodegenerative diseases (8, 14, 15). However, the effect of citicoline on stroke is elusive (for literary reviews see (16-19), even more if take into account data from the latest clinical trials that failed to show beneficial results (20, 21). These neuroprotective effects lead other authors to suggest that citicoline might have beneficial impact on several cognitive domains (22), and several trials including patients of Alzheimer disease (10) or vascular dementia (23).

Meta-analysis combines findings from independent studies to assess the clinical effectiveness of healthcare interventions (22). Using this technique, the efficacy and safety of a drug (24, 25), or its lack of efficacy, such as in the case of the promising drug dimebon (26), can be determined. 

The lack of a systematic review that put together all the information on citicoline effects on cognitive function was the starting point of this work. Thus in this study, we performed a systematic review of the literature on citicoline and its efficacy on impairment associated to neurodegenerative diseases such as alterations in mini-mental state examination, memory, attention and finally the plausible effects on basic activities of daily living.


Material and Methods

We conducted a search for all clinical trials using citicoline to improve cognitive function, in patients affected by different pathologies causing neurological disorders. The studies were found by means of a MEDLINE and and in the Cochrane Central Register of Controlled Trials (CENTRAL) searches using the keywords “Citicoline” AND “cognitive» (July 2014). The bibliographic references of the selected articles were also examined to locate other possible publications not found in the above-mentioned search. The trials that were included meet the following criteria. 1. Double-blind placebo controlled with random assignment to citicoline or placebo. 2. Inclusion of patient with altered cognitive function. 3. Specification of medication doses and formulation. 4. Written in English. We have found 99 studies. Of these, 73 were rejected for different reasons (figure 1). Of the 26 remaining studies, 14 were included in our systematic review (Table I and Figure 1). The quality of each study was determined by using Jadad score that considers aspect related to biases such as randomization, blinding and reporting of loss to follow-up (27). This instrument gives a score from 0 (the worst score) to 5 (the best score). Two investigators (NC-C, JJ), independently extracted those publications identified here that describe controlled studies of citicoline in cognitive impairment. Disagreements were resolved in discussion with a third investigator (JSGdP).

We collected data on patients´ diagnosis, dosage used, duration of treatment and follow-up, inclusion and exclusion criteria and scales used for efficacy. Results were described for four domains: mini-mental state examination, memory, attention and basic activities of daily living.

– Mini-mental state examination (MMSE) (28). The MMSE is a common, validated screening instrument that is used as a general measure of cognitive function (lower score indicate greater impairment), includes questions about basic temporal and spatial orientation, attention, language, calculation, memory fixing and constructive praxis. 

– Memory: Different scales were used to assess memory. Briefly, Randt memory test for longitudinal assessment of mild and/or moderate memory deficits (29), memory subscale of Alzheimer’s Disease Assessment Scale (ADAS) (30) used to evaluate the severity of cognitive and noncognitive behavioral dysfunctions characteristic of persons with Alzheimer’s disease, California Verbal Learning Test popular clinical and research test that claims to measure key constructs in cognitive psychology such as repetition learning, serial position effects, semantic organization, intrusions, and proactive interference (31), Logical Memory consisting in  immediate repetition of short stories presented auditory (it is a subtest of Wechsler Memory Scale, a widely used clinical scale composing a number of subtest) (32) and the Rey Auditory Verbal Learning Test (RALVT) an easy to administer test that assesses many memory domains and is, therefore, widely used in the area of clinical neuropsychology (33).

– Attention: Two tests were used for determining the subject’s attention. The Toulouse-Pieron Test and the Trail Making Test are accessible neuropsychological instruments that provides the examiner with information on a wide range of cognitive skills (11).

– Basic activities of daily living (disability): two scales were used, basically for the evaluation of self-care and mobility. Barthel Index, a scoring technique that measures the patient’s performance in 10 activities of daily life (34) and the Index of Activities of Daily Living (ADL) a method of classifying heterogeneous groups of people with chronic illnesses, disabilities and impairments, and of describing their health needs and outcomes (35).

The statistical analyses were performed comparing citicoline with placebo in terms of efficacy wherever such comparison was possible. The efficacy measures were expressed as odds ratio or standardized mean diference with the relevant confidence interval (IC95%). We have used a random effect where heterogeneity among studies was found. A funnel plot, if possible, were used to evaluate potential selection bias in the studies. Chi2 of heterogeneity and I2 inconsistency statistic were used to measure heterogeneity regarding study results. In all tests, the level of statistical significance used was p<0.05. Analyses were performed using RevMan version 5. 



Our literature search revealed 14 clinical trials that were included in our study tested the efficacy of citicoline for improving cognitive functions in patients that were affected by altered cognition pathologies, such as vascular dementia, acute stroke, and Alzheimer disease.

Effects of citicoline on MMSE

Although we found four trials including 474 patients, of which 300 were treated with citicoline using the MMSE measure to evaluate cognitive function.

In two clinical trials, citicoline efficacy was tested in patients with vascular dementia, giving contradictory results. Chandra et al reported a marked improvement on the MMSE score compared with patients taking after two months (MMSE score: 23 in citicoline group and 14.4 in placebo group) and after 10 months (MMSE score: 23 in citicoline group and 12.2 placebo group) (12). On the other hand, Cohen et al. found no significant changes in MMSE scores at 6 and 12 months (23).  

In patients with acute ischemic stroke, Clark et al., evaluated the effect of three daily doses of citicoline (500, 1000 and 2000 mg) versus placebo (36). At 12 weeks, citicoline increased the percentage of patients with an optimal outcome in the MMSE (≥25). Remarkably, this effect appeared not dose dependent, since it was observed at 500 and 2000 mg but not 1000 mg (36). 

In Alzheimer disease patients, Alvarez et al. did not detect a difference in the MMSE score between placebo and citicoline (1000 mg, 12 weeks) (10).  


Table 1 Clinical trials included in this review


Citicoline effects on memory

In table II, we have summarized the eight clinical trials, including 1890 patients, which evaluated citicoline effects on memory function (9, 10, 13, 15, 23, 37, 38). 


Table 2 Clinical trials evaluating citicoline effects on memory

N.S. Non-significant. RAVLT, Rey Auditory Verbal Learning Test. 

Two trials used the Randt Memory Test to ascertain citicoline efficacy in patients with chronic cerebrovascular disease. First, Piccoli et al. revealed that citicoline induced a constant and progressive improvement (p<0.05) (37).  Second, in a subtest of this test, Capurso el al. found a significant difference in the memory index (p<0.05) (13). However, in patients with vascular dementia, citicoline failed to improve the California Verbal Learning Test (p=0.36) and Logical Memory (p=0.5) (23). Lack of citicoline-induced positive effects were also reported by Alvarez-Sabin et al. Using the Auditory Verbal Learning Test, these authors did not detect differences in patients with post-stroke vascular cognitive impairment at 6 and 12 weeks (p=0.807 y p=0.873) (39).

In the citicoline brain injury treatment trial(COBRIT), citicoline failed to afford any improvement in the California Verbal learning Test score in patients with traumatic brain injury (38). In patients with bipolar disorder with cocaine dependence, Brown et al. reported that citicoline leads to an enhancement in the RAVLT alternative Word list (p=0.006) but not in RAVLT total Word (p=0.439) or RAVLT delayed recall (p=0.105) (15). In addition, two more trials described a positive but not statistically significant tendency to improve memory in volunteering patients with relatively inefficient memory (9) or Alzheimer disease  (10). 

Effects of citicoline on attention

We identified five trials analyzing citicoline effects on attention, enclosing a total of 1.721 patients (23, 37-40). In patients with chronic cerebrovascular disease, citicoline induced a significant decrease in the number of incorrect responses in the Toulouse-Pieron test (p<0.05) (37). Similarly, Alvarez-Sabin, at 6 (p=0.019) and 12 (p=0.014) months of treatment, evidenced less deterioration of post-stroke vascular cognitive impairment in attention-execution (Stroop Color Word Interference test, Trails A and B and Symbol digits Modalities Test, Mental control, Digit Span) (39). 

However, using the Trail Making Test scores, we did not find citicoline-induced improvements in patients affected by Alzheimer disease (p=0.74) (40), vascular dementia (p=0.58) (23) or traumatic brain injury (38).


Figure 1 Flow chart outlining the search strategy and results of the different steps



Figure 2 Forest plots showing individual and pooled odd ratio (95%) for the associations between citicoline (2000 mg and 500 mg) and Barthel index (≥95)


Effects of citicoline on basic activities of daily living

 The effect of citicoline on the patient ability to perform activities of daily living was evaluated in 5 clinical trials that included 4137 patients, 2334 of which were treated with citicoline. 

In acute ischemic stroke patients, Clark et al. evaluated citicoline efficacy in three clinical trials, leading to heterogeneous results. Interestingly, in the first trial, with citicoline administered at 500, 1000, and 2000 mg, only at a daily dose of 500 mg citicoline resulted in a Barthel-index improvement (p=0.03) (36). Their second trial was addressed to compare citicoline (500mg) versus placebo (41), but this did not yield positive results. In the third trial, the authors compared a daily dose of 2000mg citicoline versus placebo. Although initially (at 6 weeks) a higher proportion of patients in the citicoline group showed a score higher or equal to 95(placebo 21%, citicoline 27%; p=0.04), this difference was lost at 12 weeks (42). In addition, in a different trial, Davalos et al. did not find citicoline effects in this kind of patients  (20). Our meta-analysis of these data shows that citicoline did not significantly alter the Barthel index at the doses of either 500mg (OR 1.43; IC 95% 0.64-3.19)or 2000mg(OR 1.13; IC 95% 0.86-1.49) (Figure 2). 

Using the ADL scale in elderly patients with progressive cognitive impairment, Putignano et al., did not find effectiveness for citicoline, although, they denoted a trend towards favorable scores in the functional independence (43) 



Prompted by the fact that citicoline has been shown to be a useful treatment for neurodegenerative and cerebrovascular diseases, we have evaluated its ability to improve cognitive function by performing a systematic review. To do so, we focused on scales that measure aspects such as MMSE, memory, attention, and basic activity of daily living.  

Our data reveal a positive effect of citicoline on MMSE in acute ischemic stroke, which was not evidenced for other diseases where cognitive function is compromised, including Alzheimer disease or vascular dementia. However, this positive improvement was found in a single study,and only at a daily dose of 500 and 2000 mg but not 1000 mg. So, it will be interesting to corroborate these data in a new clinical trial. In addition, in vascular dementia, our study revealed contradictory results, which makes it difficult to draw solid conclusions. Furthermore, we found lack of evidence for citicoline effects on cognitive impairment associated to Alzheimer disease. This conclusion seems contradictory to the previous conclusion reached by Secades in a nice and elegant, but not systematic, review (17). 

In addition, eight studies reporting citicoline effects on memory were found. In chronic cerebrovascular disease patients, two studies yielded favorable results. However, other studies failed to show a positive effect on post-stroke vascular cognitive impairment, AD, or aging. Unfortunately, we were unable to perform a meta-analysis as the authors used different scales with different scores and thresholds to measure sensibility. These disparities constitute a handicap to find plausible positive effects.

We have also analyzed the effects of citicoline on attention. Positive results were observed in two studies performed with post-stroke patients and chronic cerebrovascular disease. However, citicoline failed to produce this positive result when the patient suffered from Alzheimer disease, traumatic brain injury, or vascular dementia.

Our last goal was focused on the effects of citicoline on the activities of daily living. Our meta-analysis, which included four trials, revealed that citicoline failed to exert beneficial effects in patients with acute ischemic stroke (Barthel index) or progressive cognitive impairment (ADL score). 

Why citicoline improves some cognitive impairments but fails to do so with others remains unknown (43, 44, 45) Pre-clinical evidence supports citicoline efficacy and an optimal neuroprotective profile in stroke animal models (7). In a recent review, Overgaard concluded that citicoline is the only drug that, in different clinical stroke trials, continuously showed neuroprotective effects (3).

However, we cannot ignore that often important causes of irreproducibility of experimental results in clinical settings are the use of large drug doses in most animal experiments (18) or the lack of methodological rigor, and these lead to an inflated treatment effect (46) Considering that citicoline is an essential intermediate in the synthesis of structural phospholipids of cell membranes and its formation from phosphorylcholine is the rate-limiting step of this biosynthetic pathway, one could hypothesize that it needs to have a strict control. In fact, citicoline is hydrolysed into choline and cytidine to be resynthesized later in the brain (47). In this scenario, long treatment periods would result in a negative feedback and result in readjustment of the available citicoline levels, yielding a non-efficient drug. Supporting this idea, Baab et al. found that phospholipid synthesis and turnover were stimulated at 6 but not 12 weeks of oral citicoline treatment. Moreover, these authors correlated results from the California Verbal learning test with an increase in phophodiesters (48). Then, only under acute damage (e.g. acute stroke), where this homeostatic response does not efficiently regulate endogenous values, citicoline administration results in an efficient protection. On the other hand, in acute events citicoline might result in an inhibition of cell death pathways. For instance, in an experimental model, citicoline markedly lowered brain edema and blood-brain barrier permeability, enhanced the activities of superoxide dismutase, increased glutathione levels, and reduced the levels of malondialdehyde and lactic acid  (49). Other mechanisms suggested to be involved include prevention of phospholipase A2 activation  (50), which is involved in transient cerebral ischemia (51). 

There is a Cochrane’s Systematic review about this topic performed by Fioravanti M and Yanagi M, that yielded different results  (52). The authors concluded that there was some evidence that CDP-choline has a positive effect on memory and behaviour. The effect on attention measures was not significant (p=0.22). Nonetheless, the characteristics of this review are different from ours since the outcome analyzed differ. For instance, the effect of citicoline on the MMSE and on activities of daily living is novel in our review. We have to acknowledge that our study presents limitations related to the difficult process of selecting trials using citicoline.  In addition, our systematic review shows the heterogeneity of trials using citicoline. This heterogeneity is present in parameters such as treatment duration, the number of patients, the follow-up period, and the scores used. Moreover, we were negatively surprised by the way the authors of the trials had reported their results. Whereas some authors gave mean scores, others categorized them when they referred to the same scale. Indeed, we found that 5 reached a Jadad score of zero (8, 14, 21, 53, 54), which is indicative of a lack of answer to relevant key questions such as «Was the study described as randomized, or as double blind?», «Was there a description of withdrawals and dropouts?»Due to these discrepancies, it is difficult to make a thorough analysis of the data and might easily lead to wrong interpretations. 

Finally, although our study was not undertaken to determine citicoline safety, we validate the general idea that citicoline presents a good safety profile. Ten of the trials included in our study described adverse events. Enclosing 2254 patients in total, 1400 were treated with citicoline. The side effects most frequently reported were effects on the central nervous system in both the citicoline (127 events, 10%) and the placebo (103 events, 13%) groups. However, we did not find significant differences between these groups.

In summary, our data suggests that citicoline may improve MMSE in acute stroke patients. However, to reach a solid conclusion for this and other chronic diseases such as Alzheimer disease and vascular dementia, we need to reach an agreement on the test scales and how to report the scores before performing more trials. Awaiting the completion of new clinical trials including higher numbers of patients in order to obtain more consistent results, we would not advise the use of citicoline as effective treatment in patients with cognitive impairment.


Ethical Standards: None disclosed.

Conflicts of Interest: The authors declare that they have not conflicts of interest.



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I. Culum, J.B. Orange, D. Forbes, M. Borrie

Health and Rehabilitation Sciences (Health and Aging), Faculty of Health Sciences, Western University, London, ON, Canada 

Corresponding Author: Ivan Culum, Health and Rehabilitation Sciences (Health and Aging), Faculty of Health Sciences, Western University, London, ON, Canada, E-mail: iculum@uwo.ca 



Introduction: The World Health Organization (WHO) recommends a diet that limits saturated fat consumption and encourages unsaturated fat consumption. A diet that is compatible with the WHO recommendations and of considerable interest to researchers interested in dementia is the Mediterranean diet (MeDi). What is known empirically at present about the MeDi and dementia is that t may have roles to play in reducing the risk factors as well as the overall risk for developing dementia. Objectives: In this cross-sectional study, we examined the macronutrient composition of the average Canadian diet (CanDi) in order to see how it may differ from the average Mediterranean diet (MeDi). Additionally, we compared how the CanDi differs between groups based on gender, age, geographical location and classification (i.e. urban vs. rural), and dementia risk. Design: The Canadian Community Health Survey (CCHS) 2.2 data were used to estimate the macronutrient composition of the CanDi for older adults (age 50+) (N = 10,503 [4,955 male, 5,548 female], mean age = 64[10.30]).  Results: The average daily macronutrient intake in a CanDi was found to be 227.7 g of carbohydrates, 78.5 g of proteins, 67.8 g of fats (21.8 g of saturated fats, 27.1 g of monounsaturated fats, and 12.4 g of polyunsaturated fats), as well as 8.3 g of alcohol and have an average energy value of 1856.9 Kcal. The energy breakdown by macronutrient in a CanDi is estimated as follows: 49.2% from carbohydrates, 16.9% from proteins, and 31.1% from fats (10% saturated, 12.3% monounsaturated, and 5.7% polyunsaturated fats). On average, the respondents did not meet the daily energy requirements for their respective age group as outlined in Canada’s Food Guide. Conclusion: The macronutrient composition of the CanDi differs not only from the MeDi, but also from previous Western diet generalizations. Of particular interest is the finding that respondents identified as being “at-risk” for developing dementia consumed significantly less of each macronutrient and less food overall than those who were identified as otherwise healthy.

Key words: Diet, aging, dementia, Mediterranean diet. 



Global average life expectancy has increased steadily from the early 20th century from 46.5 years to 70 years (1). According to experts in the United Nations Population Division, this pattern will continue into the near future. There also will be an increasing worldwide proportion of individuals over 65 years of age with those aged 85+ being the fastest growing cohort of all (1). In concert with the increasing global prevalence of older adults is the rise of chronic diseases among older adults, such as dementia, which are the leading causes of mortality among those 65 years of age and older in Canada (2, 3). 

Dementia is a syndrome in which there are persistent and progressive declines in memory, language and communication, personality, visuospatial skills and other cognitive processes such as executive functions (4). It is estimated that by 2038 approximately 1.1 million Canadians (2.8% of the overall population) will exhibit dementia (5). These estimates mean that the number of persons with dementia in Canada will more than double in just three decades (from approximately 480,000 in 2008 to approximately 1,125,000 in 2038) (5). The incidence of Alzheimer’s disease (AD), the most prevalent type of dementia, also is rising. There are 7.7 million new cases of dementia worldwide, which translates to approximately one new case every four minutes (6). It is estimated that AD will occur in 1 out of 85 persons worldwide by 2050 (7). The worldwide prevalence of AD was estimated to be 35.5 million in 2010 (8) with a quadrupling projected for 2050 (7). However, others have suggested that dementia incidence and prevalence has been on the decline in high-income European and North American nations (9, 10, 11]. While this is certainly a bit of good news, meaning that the aforementioned projections of absolute numbers of people with dementia may be a bit less dramatic, this does not mean that dementia will not remain a healthcare, economic, societal, emotional burden for years to come.

AD is the most prevalent type of dementia, followed by vascular dementia (VaD), Lewy-body dementia (LBD), and frontotemporal dementia (FTD) (6). AD and VaD account for most of the dementia cases worldwide. “Pure” AD and “pure” VaD occur less frequently than previously thought. It is common to find pathology relating to more than one dementia type in the brains of persons with dementia (PWD). The combination of pathologies of AD and VaD is called mixed dementia (MD) though no standard diagnostic tools exist for this type of pathology (12). 

To compound the rising global prevalence of dementia and the monumental care needs for those with dementia are the staggering costs of current care which are significant and increasing sharply. Estimates in 2010 for the total worldwide societal costs for dementia were USD 604 billion (6, 8), up from 315 billion in 2005 (13). Estimates based on data from the Canadian Study on Health and Aging (CSHA) reveal that annual societal costs of caring for older adults with dementia in Canada range from approximately CAD 10,000 for mild cases to CAD 38,000 for severe cases (14). Over 80% of these costs are attributed to institutionalization (15). Overall, Canadian dementia economic burden was estimated to be approximately CAD 15 billion in 2008 and is projected to increase to approximately CAD 870 billion by 2038 (5). Researchers estimated the annual cost of caring for a person with VaD to be USD 14,000 (16). Statistics Canada estimated the annual Canadian household per capita income to be CAD 42,600 (17) reinforcing further the severity and the importance of the economic impact of dementia on caregivers and to Canadian society in general. The financial burden to Canadians because of dementia, in all its forms, now and in the coming future simply cannot be ignored.

Diet and Aging

Preventive approaches designed to limit the development of chronic illnesses, such as dementia, are becoming increasingly important to researchers, clinicians, policy makers and caregivers. The preventive approaches, such as diet modifications, are most effective well before a disease manifests (primary prevention) but can be useful even after the disease emerges (secondary prevention). Prevention also can be cost-effective. While a healthy diet versus an unhealthy diet is more expensive in an immediate sense, societal and personal economic savings can be realized based on delaying disease onset. Adhering to a healthy diet can compress morbidity, that is, the overall reduction of end-of-life disease length (18). Therefore, reducing the incidence and prevalence of chronic diseases through dietary changes may improve the efficiency of health-care systems, and enhance the quality of life for those with chronic illnesses and for their caregivers. 

Healthy eating is a key component in healthy aging. Charlton (2002) demonstrates that the adoption of a healthy diet can increase overall life expectancy and can contribute to better overall health (19). While adopting a healthier diet is most effective earlier in life, it is important to note that protective benefits of a healthier diet can occur at any age (20). Unhealthy dietary habits (e.g., increased saturated fat intake) can lead to obesity that increases an individual’s chances of developing a variety of negative health outcomes such as cardiovascular disease, hypertension, hyperlipidemia, and diabetes. These conditions increase the risk of dementia in older adults and are identified as risk factors (21, 22). Minimizing these risk factors should be a key component in healthy aging.

A person’s metabolism slows down with advancing age where less energy is required to maintain normal functions. The adoption of healthier eating habits, particularly in response to age-related metabolic needs, can reduce directly the risk factors for vascular disease, which in turn can help reduce the development of dementia in most forms (e.g., AD, VaD and mixed). Findings from several longitudinal studies showed that healthier eating can result in reduced cholesterol levels (23-25) and systolic blood pressure (24). While there is no single healthy diet, the WHO recommends a diet that is limited in saturated fat consumption versus one in which there is unsaturated fat consumption. The WHO recommends that a healthy diet also includes: limiting overall energy intake from all fat sources, increasing the overall consumption of fruits and vegetables, legumes, and nuts/grains, and decreasing the intake of sodium and free sugars (26). A diet that is compatible with the WHO recommendations and of considerable interest to researchers interested in dementia is the Mediterranean diet (MeDi).

The Mediterranean Diet

The MeDi, which varies slightly among Mediterranean regions, commonly includes components such as high consumption of fish, fruits/vegetables/legumes, and grains, coupled with moderate dairy and alcohol consumption, and low meat consumption (27). Researches from Greece estimated that the average daily macronutrient intake in a MeDi consists of 255.0 g of carbohydrates, 74.5 g of proteins, 110.7 g of fats (29.8 g of saturated fats, 63.8 g of monounsaturated fats, and 9.9 g of polyunsaturated fats), as well as 14 g of alcohol, and have an average energy value of 2473 Kcal (28). Furthermore, the energy breakdown by macronutrient in a “typical” MeDi is estimated as follows: 47% from carbohydrates, 15% from proteins, and 38% from fats (10% saturated, 22% monounsaturated, and 6% polyunsaturated fats) (29). In comparison, the “typical” Western diet provides 42% of daily energy from carbohydrates, 20% from proteins, and 38% from fats (17% saturated, 14% monounsaturated, and 7% polyunsaturated fats) (30).

Since the 1960s the MeDi has received increasing scientific attention because of its association with a reduced risk of hypertension (31), coronary heart disease (32), obesity (33), as well as overall mortality (34). Researchers suggest that the MeDi may be beneficial in reducing the risk of AD and related dementias regardless of vascular comorbidity (35). Others suggest that the antioxidants typically found in olive oil compounds and red wine, components common in the MeDi, mediate vascular pathology (36, 37). Additionally, polyunsaturated fatty acids (PUFAs) (specifically omega-3 fatty acids) also may play an important role in mediating inflammatory response thereby further reducing the risk of vascular pathology (12, 38). It is likely that the MeDi is more than just a sum of its components and that its benefits are a result of multiple components working in tandem, although definitive evidence remains needed.

There is a growing body of evidence in favour of adopting the MeDi to help optimize health status and to reduce the risk of dementia. In a recent meta-analysis of studies in which a MeDi intervention was used, researchers reported that a higher adherence to the MeDi was associated with better cognitive function (and lower rate of cognitive decline), as well as an overall reduction of AD risk (39). In an earlier meta-analysis, researchers reported that an increase in MeDi adherence translated to a 10% reduction in death and/or incidence of vascular diseases as well as a 13% reduction of the incidence of neurodegenerative diseases (40). There also is evidence that adopting the MeDi reduces the risk of mild cognitive impairment (MCI) and the conversion of MCI to dementia (41). It is important to note that while MeDi research interest has been increasing over the past decade the relationship between MeDi and dementia risk remains a rising area of research activity.

Statement of Problem

What is known empirically at present about the MeDi and dementia is that it may have roles to play in reducing the risk factors as well as the overall risk for developing dementia. However, what remains unknown is how the average Canadian diet (CanDi) differs from the average Mediterranean diet (MeDi) and the implications of such differences on the development of dementia among Canadians. While previous research has focused primarily on the health benefits of either living in the Mediterranean region or the adoption of the MeDi in different regions worldwide, no investigators have published studies that examined how dietary habits of older Canadians compare to the MeDi. This is a necessary first step toward a clearer understanding of how much effort may be necessary to promote a shift toward the MeDi among Canadian older adults, particularly for those with dementia, those who are at-risk for developing dementia, or those who are otherwise healthy. 

The aim of this retrospective study was to fill this knowledge gap concerning the dietary habits of Canadian older adults. The following research questions were posed. 

Research Questions

1. What is the macronutrient composition of the typical diet of Canadian older adults (50+ years) according to the CCHS Cycle 2.2 (2004) data set?

2. Are there differences in dietary patterns between different Canadian older adult participant groups?

a. Is there a difference in dietary patterns between:

i. the young-old (51 to 70) vs. the older adult (71+) cohorts

ii. men vs. women in each of the two cohort age groups?

3. Are there differences in dietary patterns relative to geographical location (i.e., province and rural/urban areas) in Canada?

4. Are there differences in dietary patterns between “at-risk” (cognitively intact, but with vascular risk factors such as metabolic syndrome) and “healthy” groups?



Study Design

Nutritional data were mined from the Canadian Community Health Study Cycle 2.2 (42) for this between groups retrospective study. These data represent the most current and comprehensive profile of dietary habit of Canadians. Permission from and authorization to access the restricted Statistics Canada database was obtained from the Research Data Centre (RDC) through a proposal submitted to the Social Sciences and Humanities Research Council of Canada (SSHRC) by the first author (IC).


Participant responses were obtained from the existing CCHS 2.2 data set (2004) (N = 10,524). The CCHS 2.2 employed a multistage stratified cluster design that provided a sample representative of the general Canadian population in terms of age, gender, geographical location, as well as socioeconomic status (42). The computer-assisted interviews were conducted from January 14, 2004 to January 21, 2005, with a random subset of Canadian participants selected for a second interview (24-hour dietary recall). All initial interviews were conducted in respondents’ homes, with the majority of the follow-up interviews conducted over telephone (others were conducted in-person). For the purpose of this study, respondents were placed into one of two groups based on their age at the time of their interview (51 to 70 inclusive or over 70) in order to correspond with the top two age bands as outlined in the Estimated Energy Requirements section of Canada’s Food Guide (43).   

Materials and Measures

The respondents’ dietary habits were assessed via a computer-aided-interview as well as a 24-hour dietary recall in the CCHH 2.2. These data were used to determine the macronutrient composition of the CanDi for older adult Canadians. 

Ethics and Permissions

Permission to use CCHS 2.2 data was obtained from Statistics Canada through the local Research Data Centre (RDC) at Western University. The statistical analyses were vetted by the Senior Analyst at the RDC to ensure that no participant could be identified due to sub-group analysis. In accordance with RDC regulations, no raw data were removed from the RDC office. 

Data Collection

Relevant data from the CCHS 2.2 were mined at the Western University RDC and exploratory data analyses were performed. The dataset was selected because it is the most current, large survey of its kind in Canada that contains relevant dietary information. Variables of interest were age (categorized), gender, province, geographical classification (urban or rural), daily macronutrient intakes (in grams), alcohol intake (in grams), energy from all food sources (in kilocalories), percentage of energy from specific macronutrients, and dementia risk status (healthy or at-risk). The only inclusion criteria for the sample selection was age (over 50) and not missing any responses pertaining to the abovementioned variables of interest. Respondents with incomplete or missing variables of interest were not considered for this study. The macronutrient variables include carbohydrates, proteins, fats, saturated fats (SFs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs). SFs, MUFAs, and PUFAs are a subset of fats and these values are not added to the overall daily fat intake. Furthermore, there are other types of fats not accounted for by this breakdown and the total daily fat intake value, therefore, is greater than the sum of these three types. The study variables were derived from questionnaire and interview responses and are only an estimate of the macronutrient composition of the respondents’ diets. The variables were selected because they are the best available method of quantifying the CanDi given the available data.  

Data Analyses

The CCHS 2.2 data were used to estimate the macronutrient composition of the CanDi. The normality of the sample was tested using the Kolmogorov–Smirnov and test (and the Shapiro–Wilk test in one case where a sub-group size was too small for the former test). With the exception of one small sub-group (respondents from Prince Edward Island), the responses were not distributed normally. Non-parametric tests were conducted on the data. IBM SPSS Statistics 22.0 for Microsoft Windows® (IBM Corp., Armonk, USA) was used to perform the exploratory data analysis, as well as independent samples Mann-Whitney U and Kruskal-Wallis tests (corrected for tied ranks).



The inclusion criteria identified 10,524 relevant respondents. Due to missing data, 21 respondents were not used in the analyses (N = 10,503). The younger cohort (51 to 70) included 7,570 respondents (3,712 men, 3,858 women) while the older cohort (>70) included 2,933 respondents (1,243 men, 1,690 women). The mean age is 58.9 years for the younger cohort and 78.2 years for the older cohort.

The macronutrient composition of the CanDi for the respondents is presented in Table 1. The male respondents reported consuming significantly more carbohydrates, proteins, fats, SFs, MUFAs, PUFAs, and alcohol by weight (g) vs. the female respondents. Men also had a significantly higher daily caloric intake than women. Carbohydrates were the largest source of energy for both genders, followed by fats, with proteins being responsible for the least amount of energy from food sources (Table 2). Younger respondents consumed significantly more carbohydrates, proteins, fats, SFs, MUFAs, PUFAs, and alcohol by weight (g) than older respondents (Table 1). Younger respondents also had a significantly higher daily caloric intake than older respondents. Carbohydrates were the largest source of energy for both cohorts (Table 2) as well as by gender within cohorts (Table 4), followed by fats, with proteins being responsible for the least amount of energy from food sources (Tables 2 and 4). 


Table 1 Macronutrient intake (in grams) by age group, gender, geographical classification and dementia risk

* Median value is near zero due to many respondents’ non-consumption of alcohol on a daily basis


Table 2 Percentage of daily energy by source (by age group, gender, geographical classification and dementia risk)


Within the younger respondent group, men consumed significantly more carbohydrates, proteins, fats, SFs, MUFAs, PUFAs, and alcohol by weight (g) vs. women (Table 3). Men also had a significantly higher daily caloric intake than women. Carbohydrates were the largest source of energy for both genders, followed by fats, with proteins being responsible for the least amount of energy from food sources (Table 4). Within the older respondent group, men again consumed significantly more carbohydrates, proteins, fats, SFs, MUFAs, PUFAs, and alcohol by weight (g) vs. women (Table 3). Men in the older cohort also had a significantly higher daily caloric intake vs. women in the older cohort. Carbohydrates were the largest source of energy for both genders, followed by fats (Table 4), with proteins being responsible for the least amount of energy from food sources.


Table 3 Macronutrient intake (in grams) by age group and gender

* Median value is near zero due to many respondents’ non-consumption of alcohol on a daily basis


Table 4 Percentage of daily energy by source (by age group and gender)


Rural respondents consumed significantly more carbohydrates, proteins, fats, SFs, MUFAs, PUFAs, and alcohol by weight (g) vs. urban respondents (Table 1). Rural respondents also had a significantly higher daily caloric intake vs. their urban counterparts. Among provinces, there were statistically significant differences in daily carbohydrate, protein, fat, SF, MUFA, PUFA, and alcohol intakes by weight (g) (Table 5). Carbohydrates were the largest source of energy regardless of geographical classification (Table 2) or province (Table 6), followed by fats, with proteins being responsible for the least amount of energy from food sources.


Table 5 Macronutrient intake (in grams) by province

* Median value is near zero due to many respondents’ non-consumption of alcohol on a daily basis


Table 6 Percentage of daily energy by source (by province)


Respondents who were identified to be at-risk for developing dementia (i.e., diagnosed with diabetes and/or hypertension and/or hypercholesterolemia) consumed significantly fewer carbohydrates, proteins, fats, SFs, MUFAs, PUFAs, and alcohol by weight (g) vs. those who were otherwise healthy (Table 1). These respondents also had a significantly lower daily caloric intake vs. those who are otherwise healthy. Carbohydrates functioned as the largest source of energy regardless of dementia risk status (Table 2), followed by fats, with proteins being responsible for the least amount of energy from food sources. There was an estimated 3,638,971 individuals over the age 50 in Canada who are at-risk for developing dementia (1,489,170 over the age of 70) out of an estimated 8,897,946 Canadians over the age of 50. This represents approximately 41% of all individuals over the age of 50 and 60% of all individuals over the age of 70.


Table 7 Macronutrient intake (in grams) by diet type

* From Trichopoulou et al. (2006)


Table 8 Percentage of daily energy by source (by diet type)

* From Sacks & Katan (2002)



The aim of this study was to estimate the dietary habits of Canadian older adults by examining the macronutrient composition of the CanDi using the most current Canada-wide survey data. Results show a median daily intake of 212.2 g of carbohydrates, 70.5 g of proteins, and 59.1 g of fats (including 18.3 g of SFs, 23.1 g of MUFAs, and 10.1 g of PUFAs). These values translate into 49.3% of daily energy from carbohydrates, 16.0% from proteins, and 31.0% from fats. The CanDi estimate differs from the MeDi estimate based on a lower daily carbohydrate intake (-42.8 g), slightly lower protein intake (-4.0 g), and a much lower total fat intake (-51.6 g). When comparing specific fat types, the CanDi is characterized by a lower daily SF intake (-11.5 g), much lower MUFA intake (-40.7 g), and a slightly higher PUFA intake (+0.2 g). The CanDi also can be characterized by a lower daily alcohol consumption (5.7 g less than in the MeDi estimate). It is important to note that many respondents did not report that they consume any alcoholic beverages on a regular basis. When comparing mean daily energy values, the CanDi provides ~756 Kcal less energy than the MeDi (Table 7).

The CanDi, based on the Canadian Community Health Study Cycle 2.2 data used in this study, is estimated to provide 2% more energy from carbs and 1% more energy from proteins than the MeDi. The CanDi provides 7% less energy from fats. Particularly notable is the comparison between energy intake by fat types, where both the CanDi and the MeDi provide 10% of daily energy from SFs (Table 8). The CanDi varies significantly among the various comparison sub-groups (age group, gender, geographical classification, province, and dementia risk status). However, it is important to note that neither age group meets the daily energy requirements for their respective group as outlined in Canada’s Food Guide (43) for even the most sedentary lifestyle, let alone an active one. The difference in daily energy requirements is even greater when comparing group medians to the recommended guideline values. However, this is not sufficient cause for alarm due to respondents’ tendency to underestimate their overall food intake (44). The higher daily energy intake values among men vs. women also are not surprising due to their relatively larger body size, but the difference becomes smaller between genders in the older age group (though no less significant). Differences among macronutrient intakes by province are also not surprising, possibly due to Canada’s varied geography, different cultural and ethnic backgrounds, and the sheer size of the country. Further analysis should involve a comparison based on likeness of region rather than provincial borders and should include the northern territories as well (though no territorial data is available in the CCHS 2.2 and this should be kept in mind when collecting new data). While the “healthy” sub-group consumes more of each macronutrient (even the SFs), it is unlikely that their “at-risk” counterparts owe their status to a lower overall food and energy intake. It is possible that these respondents are less active and may in fact still be consuming more relative to their counterparts. This is, however, the most important finding of our study relative to dementia as it suggests that the link between diet and dementia risk merits further exploration, which has also been suggested in recent meta-analyses (45, 46). Further investigation is necessary, particularly since there is a limited availability of pharmacological treatment options for cognitive impairment and dementia (47). 

Furthermore, it is important to note that the CCHS 2.2 nutritional data is based on a single 24-hour dietary recall, with a smaller sample being invited for a follow-up interview. As such, we advise that these results be interpreted with caution, as multiple recalls are recommended in order to accurately depict an individual’s nutrient intake (48).


A limitation of this study is the age of the data. Due to increasing globalization additional foods are making their way into Canadians’ diet and this may result in significant changes of the CanDi composition. Unfortunately, no newer data exist at this time. The Canadian Federal government has not undertaken more recent national surveys of the dietary habits of Canadians. In addition, comparing PUFA intakes in this study is problematic because the CCHS 2.2 data does not provide a ratio of omega-6 to omega-3 PUFAs, though this is an inherent limitation of previous Western diet estimates as well. Bearing in mind the variance in data collection methods and sample sizes, these comparisons should be interpreted with caution and further exploration of the topic is necessary. It also is important to remember that these are only estimates of CanDi composition that are derived from responses to a questionnaire and an interview (which as noted above is another limitation in itself). Finally, the required daily energy estimates are based on a dated food guide.



Based on the available data set, the average Canadian (over the age of 50) has a mean daily intake of 212.2 g of carbohydrates, 70.5 g of proteins, and 59.1 g of fats. This includes 18.3 g of SFs, 23.1 g of MUFAs, and 10.1 g of PUFAs. This represents a 49.3% of daily energy intake from carbohydrates, 16.0% from proteins, and 31.0 from% fats. The macronutrient composition of the CanDi differs not only from the MeDi, but also from previous Western diet generalizations (49). This is not entirely unexpected. There are regional variations of the MeDi and such should be expected in the Western diet as well. Of particular interest is the finding that respondents identified as being “at-risk” for developing dementia consumed significantly less of each macronutrient and less food overall than those who were identified as otherwise healthy. Newer and richer data are needed in order to make a more accurate estimate of the current CanDi. Further research should be focused on physical activity levels in tandem with food intake, as well as taking cognitive impairment (and being at-risk for such impairment) into account in in the design phase of the study.

Conflict of Interest: None.



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A. McMurtray1,2,3, V. Krishna4, B. Nakamoto5,6, N. Diaz1,2,3, B. Mehta1,2,3, S. Aboutalib2, E. Saito1


1. Neurology Division, Los Angeles Biomedical Research Institute, Torrance, CA, USA; 2. Neurology Department, Harbor-UCLA, Torrance, CA, USA; 3. Neurology Department, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA; 4. Boston College, Chestnut Hill, MA; 5. Neurology Department, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA; 6. Neurology Department, Straub Hospital and Clinics, Honolulu, HI, USA.

Corresponding Author: Aaron McMurtray, M.D., Ph.D., Neurology Department Building N-25, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90509. USA. Phone (310) 222-3897. Fax: (310) 533-8905. E-mail: amcmurtray@dhs.lacounty.gov.



Background: Midlife cigarette smoking is associated with increased risk for both midlife neuropsychiatric symptoms and development of dementia later in life. Objective: This study was designed to extend knowledge of these relationships by assessing for increased risk of neuropsychiatric symptoms among demented outpatients related to midlife smoking habits. Design: A retrospective cross-sectional analysis. Setting: Patients seen in a community based outpatient clinic for treatment of dementia during a one year period. Participants: A total of 38 participants were included in this study, 22 with a history of midlife smoking and 16 lifetime non-smokers. Results: Midlife cigarette smoking was associated with midlife alcohol use (p = 0.023) and presence of delusions (p = 0.031) among demented outpatients. Conclusions: A history of midlife smoking is associated with increased frequency of delusions later in life among demented outpatients and may help identify those at higher risk for developing neuropsychiatric symptoms.


Key words: Dementia, Alzheimer’s disease, smoking, delusions.



High rates of cigarette smoking have previously been reported among individuals with psychiatric disorders such as depression, anxiety, and psychosis (1). Previous estimates suggest that individuals with psychiatric disorders account for up to 46% of all cigarette use in the United States (2), and that smoking prevalence among individuals with psychiatric disorders may be as high as 41%, compared to only 22% among individuals without psychiatric disorders (3).

The high co-morbidity between cigarette smoking and psychiatric disorders has been suggested to occur due to significant alterations in functioning of brain cholinergic and other neurotransmitter systems (1, 4, 5). Nicotine is reported to affect several neurotransmitter systems involved in development of psychiatric disorders. The dopamine system is the most well studied neurotransmitter system affected by nicotine intake from cigarette smoking, with brain dopamine levels altered through activation of nicotinic acetylcholine receptors on mesolimbic interneurons (6-8). Other neurotransmitter systems altered by activation of nicotinic cholinergic neurons due to smoking are less well studied and include: endogenous opioid peptides, gama- aminobutyric acid, glutamate, norepinephrine, and serotonin systems (8). Smoking induced modulation of these neurotransmitter systems links cigarette smoking to neurotransmitter imbalances associated with psychiatric disorders. For this reason, cigarette smoking has even been described as a possible form of attempted self- medication as these patients try to correct dysfunction of cholinergic and other neurotransmitter systems that may be associated with their psychiatric symptoms (1, 4).

This study was designed to extend knowledge of these relationships by assessing for increased risk of neuropsychiatric symptoms among demented outpatients related to midlife smoking habits. We hypothesized that there is an increased prevalence of neuropsychiatric symptoms such as depression, anxiety, delusions, and hallucinations among dementia patients who have a history of cigarette smoking compared to those who did not smoke. We were particularly interested in patients with Alzheimer’s Disease as the etiology of their dementing illness since this condition is associated with a gradually developing alteration of brain cholinergic function that may precede development of cognitive symptoms by many years or even start during midlife.



Subjects: Participants were adults, over the age of 18 years, who presented sequentially to a community-based dementia subspecialty clinic during a one-year period from January 1st 2012 to January 1st 2013 for evaluation and treatment of dementia. De-identified data was obtained and analyzed in a retrospective fashion for all participants. Local Institutional Review Board approval was obtained.

Standardized Evaluation: All patients underwent a standardized workup consisting of a detailed history, general physical and neurological examinations, a brain imaging study with either computed tomography or magnetic resonance imaging, laboratory blood tests for treatable causes of cognitive impairment including serum vitamin B12, folate, and TSH levels, as well as RPR and HIV testing, and a Mini-Mental State Examination (9). Midlife smoking status was determined by either self- report or report by family members or caregivers if self- report was considered unobtainable or unreliable by the examining neurologist.

Dementia Diagnosis: Diagnoses of dementia were made by a board certified neurologist according to established clinical criteria (10). Dementia severity was determined by MMSE score with mild dementia indicated by scores ranging from 21 to 25, moderate dementia by scores ranging from 10 to 20, and severe dementia by scores below 10. Presence of neuropsychiatric symptoms including depression, anxiety, delusions and hallucinations were determined by a board certified neurologist during the history and physical examination.

Statistics: Normally distributed continuous demographic factors and other continuous variables were compared between groups using two-tailed t-tests. Continuous non-parametric data was compared between groups using the Mann-Whitney U test. Frequency of occurrence of categorical variables was compared between groups using chi-square analysis or Fisher’s exact test as appropriate. All statistical calculations were performed using IBM SPSS Statistics for Windows, version 21.0.



A total of 79 patients presented to the community based dementia subspecialty clinic during the one-year retrospective study period. Of these, 38 patients met clinical diagnostic criteria for either possible or probable Alzheimer’s disease and were included in this retrospective analysis. Of the study participants, 22 had a history of midlife smoking and 16 were lifetime non- smokers. A total of 28 patients were excluded because they did not meet clinical criteria for either dementia and a total of 13 patients were excluded because an adequate and reliable midlife smoking history could not be obtained.

Overall midlife smoker and lifetime non-smoker groups were very similar and did not significantly differ in demographic factors such as mean age, dementia onset age, gender distribution, ethnicity distributions, or presence of other significant co-morbid medical problems such as hypertension, diabetes, coronary artery disease or previous stroke (See Table 1).

There was a trend towards lower mean MMSE scores among the lifelong non-smokers (mean = 13.86, S.D. = 9.670, p = 0.074) compared to midlife smokers (mean = 17.76, S.D. = 6.796). While midlife cigarette smoking was positively associated with midlife alcohol use (p = 0.023), no significant relationship was detected with midlife illicit substance use (p = 0.372). Neuropsychiatric symptoms were present in 22 of the 38 patients (57.89%), including 13 of the 22 midlife smokers (59.09%) and 9 of the 16 lifelong non-smokers (56.25%). Overall for the entire group, anxiety was present in 26.32% of the participants, delusions in 31.58%, depression in 57.89%, hallucinations in 31.58%, paranoia in 21.05%, disruptive behaviors in 44.74%, and wandering in 26.32% of the patients (See Table 2). There was no significant relationship between midlife cigarette smoking and presence of anxiety (p = 0.399), depression (p = 0.646), hallucinations (p = 0.743), or disruptive behaviors (p = 0.224). Midlife cigarette smoking, however, was positively associated with presence of delusions (p = 0.031). Additionally, trends were noted towards greater frequency of paranoia (p = 0.056) and wandering behaviors (p = 0.099) among midlife smokers compared to non-smokers (See Table 2).


Table 1: Demographic Factors of Midlife Smokers and Non-Smokers.

†S.D. = Standard Deviation; ‡AA = African American, A = Asian, C = Caucasian, H = Hispanic.


Table 2: Neuropsychiatric Symptoms among Midlife Smokers and Non-Smokers.



In this study we identified an association between midlife cigarette smoking and increased frequency of delusions later in life among a community-based sample of demented outpatients. Because cortical cholinergic deficits are known to occur in both Alzheimer’s disease and vascular dementia, it is possible that midlife cigarette smoking may represent a form of self-medication used by these patients to treat subtle cholinergic disturbance present years or even decades before frank dementia is evident. The findings of this study suggest that a history of midlife cigarette smoking may help identify dementia patients at increased risk for development of neuropsychiatric symptoms.

Presence of neuropsychiatric symptoms among dementia patients is associated with greater cost of providing care at all stages of dementia severity (11). The greater care costs occur primarily due to increased time needed for providing direct help and supervision to these patients. One recent study quantified the average increase in direct help and supervision related to the number of neuropsychiatric symptoms present, reporting an additional 10.0 hours of active help and 12.4 hours of supervision required per week for those with 1-2 neuropsychiatric symptoms. Those with 3 or more neuropsychiatric symptoms required 18.2 hours of active help and 28.7 hours of supervision per week (11). Consequently, determining factors that may predict development and identify risk of neuropsychiatric symptoms among dementia patients could allow for earlier intervention and possibly reduce care costs.

In this study, 22 of the 38 demented individuals included (58%) reported a positive midlife smoking history. This is somewhat greater than the percentage described in previous reports which typically range between 46-48% (12, 13). Similarly, the prevalence of neuropsychiatric symptoms identified in this study was lower than previous reports. Recent prevalence reports for rates of at least one neuropsychiatric symptom among demented individuals range from 69-82% (14,15), which is greater than the prevalence rate of 58% described in this study. The greater prevalence of neuropsychiatric symptoms identified in the prior studies is likely due to differences in the populations being studied, with our study including relatively fewer nursing home residents and more community dwelling individuals.

This study has several limitations. First, the cohort studied consisted of a small convenience sample that was heavily over-represented by Caucasian participants. Consequently the generalizability of the results to ethnicities not better represented in the study would require further investigation. The small sample size may have also contributed to the lack of associations detected between midlife cigarette smoking and other neuropsychiatric symptoms, and it is possible that a similar assessment

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of a larger database may yield different results. This study was also hampered by the lack of a standardized tool for assessment of neuropsychiatric symptoms as well as for assessment and quantification of midlife smoking habits. Additionally, the diagnosis of dementia was made by a single investigator and was based on clinical examination only, consequently the inter-rater reliability of the diagnosis could not be determined and there is no pathological confirmation of the clinical diagnosis.

As rates of dementia are expected to continue to rise in coming years, understanding and predicting occurrence of neuropsychiatric symptoms in this population is likely to be a topic of increasing importance. The association identified in this study between midlife smoking habits and presence of delusions suggests that midlife smoking history may help to identify dementia patients at increased risk for future development of neuropsychiatric symptoms. Further study is needed to confirm and better understand the association described in this report. Particularly useful would be a study of a larger, well characterized demented population that includes quantitative assessment of midlife smoking habits such as pack-year smoking histories and data obtained from use of standardized assessment tools for detection of neuropsychiatric symptoms.


Funding: This work was supported by CTSI Grant UL1TR000124.

Conflicts of interest: None of the authors report any conflicts of interests.




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A. Malara, G. Sgrò, F. Ceravolo, G. Curinga, G.F. Renda, F. Spadea, V. Rispoli


Scientific Commettee of National Association of Nursing Home for Third Age (ANASTE) Calabria, Lamezia Terme (CZ), Italy

Corresponding Author: Alba Malara, Scientific Commettee of National Association of Nursing Home for Third Age (ANASTE) Calabria, Lamezia Terme (CZ), Italy E-mail: alba.doc@tiscali.it, mobile phone: +39.340.6621250, fax: +39.0968.400478



Backgrounds: The International Classification of Functioning, Disability and Health (ICF) is a suitable tool to standardize the status of health and disability. A previous study, carried out on 546 subjects included in the database ANASTE (National Association of Nursing Home for Third Age) Calabria, showed that 78.43% of the patients suffered from cognitive impairment whereas 52% had a severe degree of dementia. 65% of them was suffering from Alzheimer’s Disease (AD), whereas 23% from vascular dementia (VD). Objectives: Aim of this study was to analyse the prevalence of functional impairments, activity limitations and participation restrictions of patients affected by AD and VD. Design: Observational descriptive study. Setting: Nursing Homes ANASTE Calabria. Participants: 10 patients with probable AD (ADPr) and 10 patients affected Citalopram by probable VD (VDPr). Measurements: All patients were underwent multidimensional geriatric assessment. The profiles of disability ICF, were expressed in terms of Capacity and Performance, and coded according to mild, medium, severe and complete disability. Environmental factors were skilled in facilitator or no facilitator. Results: The patients with ADPr displayed a severe impairment of functional status, and advanced clinical stage requiring higher care burden compared with VDPr patients. The ICF assessment showed that the global and specific Mental Functions, Communication and Interpersonal Relationships were more reduced in patients with ADPr respect those with VDPr. Conclusions: The identification of a ICF checklist of various forms of dementia, might provides a more detailed description of the profiles of disability and improving therapeutic, rehabilitative interventions and psico-social care.

Key words: ICF, dementia, nursing home.


The International Classification of Functioning, Disability and Health (ICF) was published by the World Health Organization (WHO) in 2001 to standardize descriptions of health and disability (1). ICF organizes information in three components:

– The Body construct, which comprises two classifications, one for body functions, and another for body structure. Body functions and body structures refer to the human organism as a whole, it includes the brain and its functions, (i.e. the mind).

– The Activities and Participation constructs denote the aspects of functioning from both an individual and social perspective. The domains of activity and participation are listed in a single list that includes the large range of areas of life, by learning basic to social tasks.

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– The Environmental factors make up the physical environment, social environment in which people live and conduct their lives. The factors are external to individuals and can have a positive or negative effect on participation, activities or on the individual’s body function or structure. The Personal factors are the individual background of an individual’s life, regardless of their health condition. These may include age, race, sex, education, experience, personality and character style, aptitudes, fitness, lifestyle, education, coping styles, social background, profession (2).

Each of the components can be expressed in terms of both positive and negative influence. The negative aspects are defined as «impairment» (dysfunction or loss of BF), «limitation of Activity» (individual difficulty in performing a particular activity) or «restriction of Participation» (individual problems in involvement in life http://abilifygeneric-online.com/catalog/Depression/Paxil.htm situations) (3). Impairments of structure can involve an anomaly, defect, loss or other significant deviation in body structures. Impairments can be temporary or permanent; progressive, regressive or static; intermittent or continuous. Difficulties or problems of these domains can arise when there is a qualitative or quantitative alteration in the way in which the functions of these domains are carried out. These characteristics are captured in further descriptions, mainly in the codes, by means of qualifiers. The positive aspects are expressed as AP codes, that identify profiles of mild, serious and complete disability, expressed in terms of «Capacity» and «Performance». The Capacity qualifier describes the highest level of functioning of a person to perform a task; the Performance describes what a person does, in actual conditions, considering all available environmental factors (instrumental and personal). Differences between Capacity and Performance qualifiers indicate the presence of environmental factors that facilitate or hinder the operating profile (1). ICF is a multi-purpose classification designed to serve various disciplines and different sectors. Its specific aim is to provide a scientific basis for understanding and studying health states and health-related outcomes, and their determinants; and to establish a common language for describing health states that will permit comparison of data across countries, health care disciplines and services. Several efforts have been implemented to develop the use of ICF codes in geriatric care settings, improving appropriate qualifications for each code according to user interest (4). ICF has an important role in the clinical setting to identify the patient who requires multiple complex performance, and to evaluate the results of medical treatments, surgical, rehabilitative, palliative, undertaken in connection with such problem. At the same time, ICF takes an important role in the organizational-management, since based on the problems and strengths of the individual, being able to indicate the range of services appropriate to the care, treatment and rehabilitation (5).

In 2011 we processed and analysed, by the database of ANASTE (National Association of Nursing Home for Third Age) Calabria, data coming from 546 subjects resident in ANASTE’s Nursing Homes. This study showed that 78.43% of the patients suffered from cognitive impairment whereas 52% had a severe degree of dementia. Was estimated, according to the ICD9 codes, that 65% of patients with dementia was suffering from Alzheimer’s Disease (AD), whereas 23% had vascular dementia (VD). The assessment of disability, by the ICF model for patients with dementia, allows us to formulate a dynamic functional-profile and identify the associations among health conditions, environmental and personal factors with disability levels.


A network of Long Term Care (LTC) Facilities, consisting of Nursing Homes and structures organization for Extensive Rehabilitation, is operating in the care of the frail elderly in Calabria. The access of these facilities is regulated according to the guidelines provided by the Calabria Region (DGR 685/2002, DGR 695/2003, LR 29/2008, DGR 3137/1999). This is an observational descriptive study carried out on a sample of residents, accross in two nursing homes associated to ANASTE Calabria at June 2011. The present study was conducted by carrying out the customary practice of care, provided to all patients who belong to the LTC ANASTE Calabria, and nursing care didn’t involve any different procedures. At the moment of admission in LTC the informed consent of the patients and/or their reference was acquired for daily care practice and use of their personal data. In brief, we used the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer’s Disease and Related Disorders Association (NINCDS/ADRA) (6) criteria for diagnosis of Alzheimer’s disease (AD), and moreover the criteria of National Institute for Neurological Disorders and Stroke- Association Internationale puor la Recherche et Enseignement en Neusoscience (NINCDS-AIREN) (7) was used to diagnose vascular dementia. We enrolled 10 patients (7 F and 3M, mean age 69 ± 17 years) with probable AD (ADPr), according to the NINCDS-ADRDA criteria, and 10 patients (4 Fe and 6 M, mean age 88 ± 4.8 years) affected by VD Probability (VDPr), according to NINDS-AIREN criteria.

All patients underwent multidimensional geriatric assessment. The clinical diagnosis of dementia was firstly investigated by an interview through a detailed personal as well as family history and, subsequently, confirmed by the administration of psychometric tests. All patients fulfilled the criteria for dementia as described in the Diagnostic and Statistical Manual of Mental Disorders, Revised Fourth Edition (DSM IV) (8). The diagnosis of chronic pain was made according to ICD9-CM Official (9).The cognitive evaluation, was conducted by Folstein’s Mini-Mental State Examination (MMSE) (10). According to MMSE, the patients were affected by severe, moderate or slight cognitive impairment, if MMSE score ranging 0-10, 11-20 or 21-23 respectively. The Clinical Dementia Rating (CDR) (11) was used for the staging of disease. The functional state was evaluated by the use of the Activity Daily Living scale (ADL) (12) and Barthel Index (BI) (13), in both scale a lower score indicate a worse of functional state. The burden of care was calculated in minutes assistance/day according to the Resource Utilization Group (RUG) III (14). The profiles of disability, by ICF, has been expressed in terms of Capacity and Performance. The Performance qualifier indicates the degree of Participation and/or Restriction in describing the current performance of the people in a task or action in their real environment. This context includes the environmental factors (physical, social and attitudinal) that can be coded using the Environmental Factors. Performance can be understood as «involvement in a life situation» or «lived experience» of people in the actual context in which they live. The Capacity qualifier indicates the degree of limitation by describing the person’s ability to perform a task or an action. The Capacity qualifier focuses on limitations that are inherent or intrinsic features of the people themselves, due to the state of health of the person, without assistance of environmental factors (15). The components of the ICF classification are indicated with the letters b (body functions), s (body structures), d (dimension Activity/Partecipation) and e (environmental factors) and are followed by a four-digit numeric code. The ICF also provides a scale of qualification for generic categories, where 0 stands for «no problem» (0-4% limitation/impairment), 1 for «sensitive issue» (5-24% limitation/impairment), 2 for «moderate problem» (25-49% limitation/impairment), 3 for «serious problem» (50-95% limitation / impairment), and 4 for «complete problem» (96-100% limitation/impairment) (1). According to th ICF guidellnes, only the explicit and specific information were coded, such as those observed by the operator, through the patient’s behavior, and codified in the categories closest to the operation observed, regardless of the patient’s health. For the «Functions of the body» of the ICF components and «Activities and Participation», were calculated the prevalence of impairments and limitations in both the AD group and VD group. The disability were coded according to the following scale: mild (5-24%), medium (25-49%), severe (50-95%), complete (96 to 100%). The environmental factors (personal and instrumental) were listed as able in Barrier or No barrier, facilitator or No Facilitator (15).


Patients with ADPr exhibited a severe impairment of functional status (ADL: 0.9 ± 1.5 and BI: 19 ± 24.8 IB), and an advanced clinical stage of dementia (CDR: 3.8 ± 0.6). Instead of patients with VDPr showed less impairment of functional status (ADL: 1.1 ± 0,87 and BI; 31.6 ± 24.9), but an advanced clinical stage of dementia too (CDR of3.4 ± 0.69). The care burden calculated according RUG III indicated an increased need of care in minutes of care for patients with AD Pr (327,2 min/day/one) compared with patients with VD Pr (213 min/day/one) (Tab1). In patients with dementia, relevant information, those related to Mental Functions (b1.) and those related to restrictions in performance associated with Mental Functions, were found; in particular, the items relating to Communication (d3), Interaction and Relationships (d7), mobility (d4) and self-care (d5), civil and social life of the community (d9), while learning and applying knowledge (d1), home life (d6) and Area of life Main (d8) were not applicable in this patient population. The global and specific Mental Functions, Communication and Interpersonal Relationships were more reduced in patients with ADPr compared with VDPr (Fig.1, 2 and 3), whereas in this group there were no significant differences about mobility and personal care. The assessment of the ICF AP, according to the qualifier “Capacity”, showed that 60% of ADPr patients and 40% of VDPr patients had a complete disability, while 40% of ADPr patients and 60% of VDPr patients showed a severe disability. Instead of observation according to the ICF qualifier “Performance”, which takes into account environmental factors, showed a improvement of disability in both groups (Fig.4). The following environmental factors have been encoded Facilitator: as E355 (health professionals, nurses, rehabilitation therapists), E360 (educators, social workers.) E110 (drugs) and E115 (devices).

Table 1 Population and measurement characteristics

Notes: Alzheimer Disease Probable (ADPr); Vascular Dementia Probable (VDPr); Mini Mental State Examination (MMSE); Clinical Dementia Rating (CDR); Activities of Daily Living (ADL); Barthel Index (BI) Care Need by Resource Utilization Groups-III.

Figure 1 Impairments in ADPr and VDPr patients relating to the chapters: Mental Functions in the ICF component of Body Fuctions




The aim of this study is to describe the profiles of disability ICF across Activity and Partecipations domains in a cohort of residents suffering from ADPr and VDPr, to verify the effect of the environmental factors such as barrier or no barrier, facilitator or no facilitator and, finally, to sketch a checklist for the two forms of dementia. The ICF is based on a universal model that theoretically can be applied regardless of culture, age or care settings. The diagnosis alone does not explain what patients can do, what they need, and what can be the impairment of their functional status. The ICF allows us to obtain information on the operation of individuals and therefore plays an important role in the clinical setting to identify complicated patients, to evaluate the results of the medical treatment, rehabilitation and care. The ICF takes on an important role in the organizational-management, indicating the range of services that are appropriate for each treatment (16). In Italian Nursing homes, all clinical activity and care given to patients with dementia, is planned by the multi-professional equipe, with a bio-psycho-social approach, through an operational tool called Personalized Care Plan (PCP). PCP is the main tool in the clinical-organizational pathways of care particularly for patients with dementia. The PCP developed through the use of ICF, can define goals, interventions, and related health professionals, for each detected need. The ICF, compared with other rating scales of disability and the burden of care, ADL, Barthel Index or RUGIII, has allowed to include the assessment of the environmental context of dementia patients: environmental factors such as nurses, rehabilitation therapists, educators, social workers, drugs, and devices in generally, that have proven to be important facilitators. Moreover, the use of the ICF has also permitted to plan the interventions of care for patients with dementia, and taking into account important aspects of daily life, usually less considered, such as communication, social relationships, recreation and free time. The ICF is a tool that allows to go beyond the negative focus of the impairment of functions and structures of the body, to assess the complexity of living with dementia. In the field of clinical management and about the quality of life for these patients, the latter task is of great importance.The present study, despite the small sample number, shows that the goals of care processed according to the indicators of Capacity and Performance, allow an improvement of disability in ADPr and VDPr patients. This study also allows us to identify one preliminary spectrum of problems, limitations and restrictions of the most common functioning and disability in these two patients groups. The identification of a specific checklist of disease, provides a more detailed description of the profiles of disability in the various forms of dementia and helps caregivers to deduce what interventions have to be made. There are different protocols for evaluation and classification systems of disability based on ICF for other chronic diseases, such as chronic widespread pain, osteoporosis, chronic ischemic heart disease, diabetes mellitus, obstructive pulmonary diseases, breast cancer, depression, and stroke (17). The ICF core-sets contains the full spectrum of the problems of patients with a specific health condition and / or in a given clinical environment (18). It would be useful to also individuate a core-sets for the various forms of dementia, to improve the interventions and to have the possibility to verify the efficiency over a time period. The results of our study may be an initial contribution to this, but more researchs is needed on the development of the relevant ICF domains of this disease, http://cymbaltaonline-pharmacy.com/ especially taking into account other comorbidities such as metabolic and cardiovascular problems. The interventions, based on the ICF model, are able to orient the assistance and rehabilitation programs, improving the activities and participation in dementia patients, this may also induce a positive effect on their cognitive impairment and their quality of life.

Figure 2 Limitation or restriction in ADPr and VDPr patients, relating to the chapters: Comunications in the ICF component ‘Activities and Participation’

Figure 3 Limitation or restriction in ADPr and VDPr patients, relating to the chapters: Interpersonal Interactions and Relationship in the ICF component ‘Activities and Participation’

Figure 4 Prevalance of ICF disability in ADPr e VDPr patients according to the qualifier Capacity and Performance


Acknowledgments: We thank the following Nursing Homes, for the recruitment of patients: RSA “San Domenico”, Lamezia Terme (CZ) Italy, RSA “Villa Elisabetta” Cortale, (CZ) Italy, RSA “Ippolito Dodaro”, Falerna (CZ) Italy.

Funding: This study did not receive any funding for its implementation.

Disclosure: The authors report no conflicts of interest in this work.

Ethics Standards: The experiments described in this manuscript comply with the current Italian laws.


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