Catherine Féart

Adherence to a Mediterranean Diet, Cognitive Decline, and Risk of Dementia

CONTEXT Higher adherence to a Mediterranean-type diet is linked to lower risk for mortality and chronic diseases, but its association with cognitive decline is unclear. OBJECTIVE To investigate the association of a Mediterranean diet with change in cognitive performance and risk for dementia in elderly French persons. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of 1410 adults (> or = 65 years) from Bordeaux, France, included in the Three-City cohort in 2001-2002 and reexamined at least once over 5 years. Adherence to a Mediterranean diet (scored as 0 to 9) was computed from a food frequency questionnaire and 24-hour recall. MAIN OUTCOME MEASURES Cognitive performance was assessed on 4 neuropsychological tests: the Mini-Mental State Examination (MMSE), Isaacs Set Test (IST), Benton Visual Retention Test (BVRT), and Free and Cued Selective Reminding Test (FCSRT). Incident cases of dementia (n = 99) were validated by an independent expert committee of neurologists. RESULTS Adjusting for age, sex, education, marital status, energy intake, physical activity, depressive symptomatology, taking 5 medications/d or more, apolipoprotein E genotype, cardiovascular risk factors, and stroke, higher Mediterranean diet score was associated with fewer MMSE errors (beta = -0.006; 95% confidence interval [CI], -0.01 to -0.0003; P = .04 for 1 point of the Mediterranean diet score). Performance on the IST, BVRT, or FCSRT over time was not significantly associated with Mediterranean diet adherence. Greater adherence as a categorical variable (score 6-9) was not significantly associated with fewer MMSE errors and better FCSRT scores in the entire cohort, but among individuals who remained free from dementia over 5 years, the association for the highest compared with the lowest group was significant (adjusted for all factors, for MMSE: beta = -0.03; 95% CI, -0.05 to -0.001; P = .04; for FCSRT: beta = 0.21; 95% CI, 0.008 to 0.41; P =.04). Mediterranean diet adherence was not associated with the risk for incident dementia (fully adjusted model: hazard ratio, 1.12; 95% CI, 0.60 to 2.10; P = .72), although power to detect a difference was limited. CONCLUSIONS Higher adherence to a Mediterranean diet was associated with slower MMSE cognitive decline but not consistently with other cognitive tests. Higher adherence was not associated with risk for incident dementia.

Searching for an Operational Definition of Frailty: A Delphi Method Based Consensus Statement. The Frailty Operative Definition-Consensus Conference Project

BACKGROUND There is no consensus regarding the definition of frailty for clinical uses. METHODS A modified Delphi process was used to attempt to achieve consensus definition. Experts were selected from different fields and organized into five Focus Groups. A questionnaire was developed and sent to experts in the area of frailty. Responses and comments were analyzed using a pre-established strategy. Statements with an agreement more than or equal to 80% were accepted. RESULTS Overall, 44% of the statements regarding the concept of frailty and 18% of the statements regarding diagnostic criteria were accepted. There was consensus on the value of screening for frailty and about the identification of six domains of frailty for inclusion in a clinical definition, but no agreement was reached concerning a specific set of clinical/laboratory biomarkers useful for diagnosis. CONCLUSIONS There is agreement on the usefulness of defining frailty in clinical settings as well as on its main dimensions. However, additional research is needed before an operative definition of frailty can be established.

Fish, docosahexaenoic acid and Alzheimer's disease.

Cognitive decline in the elderly, particularly Alzheimers disease (AD), is a major socio-economic and healthcare concern. We review here the literature on one specific aspect of diet affecting AD, that of the omega3 fatty acids, particularly the brains principle omega3 fatty acid - docosahexaenoic acid (DHA). DHA has deservedly received wide attention as a nutrient supporting both optimal brain development and for cardiovascular health. Our aim here is to critically assess the quality of the present literature as well as the potential of omega3 fatty acids to treat or delay the onset of AD. We start with a brief description of cognitive decline in the elderly, followed by an overview of well recognized biological functions of DHA. We then turn to epidemiological studies, which are largely supportive of protective effects of fish and DHA against risk of AD. However, biological studies, including blood and brain DHA analyses need careful interpretation and further investigation, without which the success of clinical trials with DHA may continue to struggle. We draw attention to some of the methodological issues that need resolution as well as an emerging mechanism that may explain how DHA could be linked to protecting brain function in the elderly.

Chronic Low-Grade Inflammation in Elderly Persons Is Associated with Altered Tryptophan and Tyrosine Metabolism: Role in Neuropsychiatric Symptoms

BACKGROUND Neuropsychiatric symptoms are common complaints of elderly persons. Recent data suggest that chronic low-grade inflammation, a fundamental characteristic of aging, plays a role. Effects might rely on the influence of inflammation on the activity of two enzymatic pathways, the indoleamine-2,3-dioxygenase (IDO) and the guanosine-triphosphate-cyclohydrolase-1 (GTP-CH1) pathways, which are involved in the biosynthesis of monoamines. The present study assessed this possibility in 284 healthy elderly subjects drawn from the Three-City cohort. METHODS Assays included the measurement of serum interleukin-6 and C-reactive-protein, as inflammatory markers; tryptophan, kynurenine, and their ratio as index of IDO activity; and neopterin, phenylalanine, tyrosine, and nitrite, as markers of GTP-CH1 activity. In addition, structured assessments of depressive symptomatology, fatigue, and general behavioral/neurovegetative symptoms were performed. RESULTS As expected, age correlated significantly with concentrations of immune markers and neuropsychiatric symptoms. Increased inflammation was related to reduced tryptophan concentrations and increased kynurenine levels, suggestive of IDO-induced increased tryptophan catabolism. In addition, inflammation was associated with increases in neopterin and nitrite levels and in phenylalanine concentrations at the expense of tyrosine. Interestingly, increased tryptophan catabolism was associated with the depressive symptoms of lassitude, reduced motivation, anorexia, and pessimism. In contrast, variations in markers of GTP-CH1 activity correlated more with neurovegetative symptoms, including sleep disturbance, digestive symptoms, fatigue, sickness, and motor symptoms. CONCLUSIONS These findings show that chronic low-grade inflammation in aging is associated with alterations in enzymatic pathways involved in monoamine metabolism and suggest that these alterations might participate in the pathophysiology of neuropsychiatric symptoms in elderly persons.

Mediterranean diet and cognitive function in older adults.

Purpose of reviewThe effectiveness of the Mediterranean diet in reducing the prevalence of cardiovascular and chronic diseases has been largely evidenced. Although nutrition constitutes an interesting approach in preventing age-related brain disorders, the association between the Mediterranean-style diet and cognitive functions has been very occasionally explored. Recent findingsResults are provided from only two recent prospective cohorts of older Americans and French individuals (≥65 years) on the relationship of Mediterranean diet to cognitive functions. A high adherence to the Mediterranean diet has been associated with slower cognitive decline, with reduced risk of mild cognitive impairment conversion to Alzheimers disease and with reduced risk of Alzheimers disease. SummaryThe possibility that the Mediterranean diet may affect not only the risk for Alzheimers disease, but also the evolution of cognitive performances a long time before the clinical diagnosis of dementia and subsequent disease course constitutes major promising results. Replication of these results in other populations seems necessary to allow their generalization and to propose the Mediterranean diet as a potential preventive approach against cognitive decline or dementia in addition to its expected benefits against many other unfavorable outcomes in a public health perspective.

Potential benefits of adherence to the Mediterranean diet on cognitive health

The purpose of this review was to update available knowledge on the relationship between adherence to the Mediterranean diet (MeDi) and cognitive decline, risk of dementia or Alzheimers Disease (AD), and to analyse the reasons for some inconsistent results across studies. The traditional MeDi has been recognised by the United Nations Educational Scientific and Cultural Organisation as an Intangible Cultural Heritage of Humanity. This dietary pattern is characterised by a high consumption of plant foods (i.e. vegetables, fruits, legumes and cereals), a high intake of olive oil as the main source of fat, a moderate intake of fish, low-to-moderate intake of dairy products and low consumption of meat and poultry, with wine consumed in low-to-moderate amounts during meals. Beyond the well-known association between higher adherence to the MeDi and lower risk of mortality, in particular from CVD and cancer, new data from large epidemiological studies suggest a relationship between MeDi adherence and cognitive decline or risk of dementia. However, some inconsistent results have been found as well, even in Mediterranean countries. In this review, we analyse the reasons likely to explain these discrepancies, and propose that most of these differences are due to variations in the methodology used to assess MeDi adherence. We also discuss the possibility of residual confounding by lifestyle, that is, greater adherents to the MeDi also have a healthier lifestyle in general, which can favourably affect cognition. In conclusion, large-scale studies in various populations with common methodology are required before considering the MeDi as an optimal dietary strategy to prevent cognitive decline or dementia.

Olive oil consumption, plasma oleic acid, and stroke incidence The Three-City Study

Objective: To determine whether high olive oil consumption, and high plasma oleic acid as an indirect biological marker of olive oil intake, are associated with lower incidence of stroke in older subjects. Methods: Among participants from the Three-City Study with no history of stroke at baseline, we examined the association between olive oil consumption (main sample, n = 7,625) or plasma oleic acid (secondary sample, n = 1,245) and incidence of stroke (median follow-up 5.25 years), ascertained according to a diagnosis validated by an expert committee. Results: In the main sample, 148 incident strokes occurred. After adjustment for sociodemographic and dietary variables, physical activity, body mass index, and risk factors for stroke, a lower incidence for stroke with higher olive oil use was observed (p for trend = 0.02). Compared to those who never used olive oil, those with intensive use had a 41%(95% confidence interval 6%–63%, p = 0.03) lower risk of stroke. In the secondary sample, 27 incident strokes occurred. After full adjustment, higher plasma oleic acid was associated with lower stroke incidence (p for trend = 0.03). Compared to those in the first tertile, participants in the third tertile of plasma oleic acid had a 73% (95% confidence interval 10%–92%, p = 0.03) reduction of stroke risk. Conclusions: These results suggest a protective role for high olive oil consumption on the risk of stroke in older subjects.

Dietary omega 3 polyunsaturated fatty acids and Alzheimer's disease: interaction with apolipoprotein E genotype

Epidemiological studies suggest a protective role of omega-3 poly-unsaturated fatty acids (n-3 PUFA) against Alzheimers disease (AD). However, most intervention studies of supplementation with n-3 PUFA have yielded disappointing results. One reason for such discordant results may result from inadequate targeting of individuals who might benefit from the supplementation, in particular because of their genetic susceptibility to AD. The ε4 allele of the apolipoprotein E gene (ApoE) is a genetic risk factor for late-onset AD. ApoE plays a key role in the transport of cholesterol and other lipids involved in brain composition and functioning. The action of n-3 PUFA on the aging brain might therefore differ according to ApoE polymorphism. The aim of this review is to examine the interaction between dietary fatty acids and ApoE genotype on the risk for AD. Carriers of the ε4 allele tend to be the most responsive to changes in dietary fat and cholesterol. Conversely, several epidemiological studies suggest a protective effect of long-chain n-3 PUFA on cognitive decline only in those who do not carry ε4 but with inconsistent results. An intervention study showed that only non-carriers had increased concentrations of long-chain n-3 PUFA in response to supplementation. The mechanisms underlying this gene-by-diet interaction on AD risk may involve impaired fatty acids and cholesterol transport, altered metabolism of n-3 PUFA, glucose or ketones, or modification of other risk factors of AD in ε4 carriers. Further research is needed to explain the differential effect of n-3 PUFA on AD according to ApoE genotype.

Metabolic syndrome and cognitive decline in French elders The Three-City Study

Objective: To examine associations between metabolic syndrome (MetS) and its individual components with risk of cognitive decline on specific cognitive functions. Methods: Participants were 4,323 women and 2,764 men aged 65 and over enrolled in the longitudinal Three-City Study. Cognitive decline, defined as being in the worst quintile of the distribution of the difference between baseline score and either 2- or 4-year follow-up, was assessed by the Mini-Mental State Examination (MMSE, global cognitive function), the Isaacs Set Test (IST, verbal fluency), and the Benton Visual Retention Test (BVRT, visual working memory). MetS was defined by National Cholesterol Education Program–Adult Treatment Panel III criteria (at least 3 of 5 cardio-metabolic abnormalities: hypertension, high waist circumference, hypertriglyceridemia, low high-density lipoprotein [HDL] cholesterol, hyperglycemia). Proportional hazards models were adjusted for age, gender, educational level, center, baseline cognitive score, APOE4 genotype, and other potential confounders. Results: MetS at baseline was associated with an increased risk of cognitive decline on MMSE (hazard ratio [HR] = 1.22 [1.08–1.37]; p = 0.001) and BVRT (HR = 1.13 [1.01–1.26]; p = 0.03) but not on IST (HR = 1.11 [0.95–1.29]; p = 0.18). Among MetS components, hypertriglyceridemia and low HDL cholesterol were significantly associated with higher decline on MMSE; diabetes, but not elevated fasting glycemia, was significantly associated with higher decline on BVRT and IST. Conclusions: MetS as a whole and several of its components had a negative impact on global cognitive decline and specific cognitive functions in older persons.

Energy, macronutrient and fatty acid intake of french elderly community dwellers and association with socio-demographic characteristics : data from the bordeaux sample of the Three-City Study

Few data are available regarding dietary habits of the elderly, in particular about fatty acid consumption, whereas these are major risk or protective factors of several age-related diseases. The aim of the present study was to characterise the dietary intake of a French elderly population in terms of energy, macronutrients and fatty acids based on their socio-demographic characteristics. The study population (age range 67.7-94.9 years) consisted of 1786 subjects from Bordeaux (France), included in the Three-City cohort. Dietary assessment was performed by a 24 h recall, allowing the estimation of energy, protein, carbohydrate, total fat, SFA, MUFA and PUFA intakes. Socio-demographic characteristics (age, sex, marital status, educational level and income), practice of sports and BMI were registered. Total energy intake (EI) was lower in women and in older participants ( > or = 85 years) but higher in single subjects. Higher EI was associated with higher income, but not with educational level. Mean contribution of macronutrients to EI (protein 18%, carbohydrate 46% and total fat 31%) was higher in women than men, except for alcohol. The oldest individuals consumed less protein and more mono- and disaccharides. Excess saturated fat intake (43% of total fat), associated with a relative deficit in MUFA consumption (36% of total fat), was observed. The mean 18:2n-6:18:3n-3 ratio was 9.9 and decreased with higher educational level. The present results suggest that being female, older age, being widowed and low income level could be considered as risk factors of inadequate dietary intake.