Cécilia Samieri

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.

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.

ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies.

IMPORTANCE The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. OBJECTIVE To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5ω-3), docosapentaenoic acid (DPA; 22:5ω-3), and docosahexaenoic acid (DHA; 22:6ω-3) and plant-derived α-linolenic acid (ALA; 18:3ω-3) for incident CHD. DATA SOURCES A global consortium of 19 studies identified by November 2014. STUDY SELECTION Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ω-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, ω-6 levels, and FADS desaturase genes. MAIN OUTCOMES AND MEASURES Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ω-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the ω-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ω-3 fatty acids are associated with a modestly lower incidence of fatal CHD.

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.

Mediterranean diet and cognitive function in older age.

Background: Adherence to a Mediterranean diet may help prevent cognitive decline in older age, but studies are limited. We examined the association of adherence to the Mediterranean diet with cognitive function and decline. Methods: We included 6174 participants, aged 65+ years, from the cognitive substudy of the Women’s Health Study. Women provided dietary information in 1998 and completed a cognitive battery 5 years later, followed by two assessments at 2-year intervals. The primary outcomes were composite scores of global cognition and verbal memory. The alternate Mediterranean diet adherence nine-point score was constructed based on intakes of vegetables, fruits, legumes, whole grains, nuts, fish, red and processed meats, moderate alcohol, and the ratio of monounsaturated-to-saturated fats. Results: After multivariable adjustment, the alternate Mediterranean diet score was not associated with trajectories of repeated cognitive scores (P for score quintiles medians-x-time interaction = 0.26 for global cognition and 0.40 for verbal memory), nor with overall global cognition and verbal memory at older ages, assessed by averaging the three cognitive measures (P trend = 0.63 and 0.44, respectively). Among alternate Mediterranean diet components, a higher monounsaturated-to-saturated fats ratio was associated with more favorable cognitive trajectories (P for ratio quintiles medians-x-time = 0.03 for global cognition and 0.05 for verbal memory). Greater whole grain intake was not associated with cognitive trajectories but was related to better averaged global cognition (P trend = 0.02). Conclusions: In this large study of older women, we observed no association of the Mediterranean diet with cognitive decline. Relations between individual Mediterranean diet components, particularly whole grains, and cognitive function merit further study.

Plasma long-chain omega-3 fatty acids and atrophy of the medial temporal lobe

Objective: The long-chain ω-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are potential candidates for interventions to delay Alzheimer disease (AD), but evidence from clinical studies is mixed. We aimed at determining whether plasma levels of EPA or DHA predict atrophy of medial temporal lobe (MTL) gray matter regions in older subjects. Methods: A total of 281 community dwellers from the Three-City Study, aged 65 years or older, had plasma fatty acid measurements at baseline and underwent MRI examinations at baseline and at 4 years. We studied the association between plasma EPA and DHA and MTL gray matter volume change at 4 years. Results: Higher plasma EPA, but not DHA, was associated with lower gray matter atrophy of the right hippocampal/parahippocampal area and of the right amygdala (p < 0.05, familywise error corrected). Based on a mean right amygdala volume loss of 6.0 mm3/y (0.6%), a 1 SD higher plasma EPA (+0.64% of total plasma fatty acids) at baseline was related to a 1.3 mm3 smaller gray matter loss per year in the right amygdala. Higher atrophy of the right amygdala was associated with greater 4-year decline in semantic memory performances and more depressive symptoms. Conclusion: The amygdala, which develops neuropathology in the early stage of AD and is involved in the pathogenesis of depression, may be an important brain structure involved in the association between EPA and cognitive decline and depressive symptoms.

Mediterranean diet and cognitive health: an update of available knowledge.

Purpose of reviewNutrition constitutes an interesting approach for the prevention of age-related brain disorders. The objective of this review was to examine the most recent evidence on the association between adherence to a Mediterranean diet (MeDi) and cognitive health among elderly individuals. Recent findingsBased on available epidemiological studies, two meta-analyses published in 2013 have underlined a protective effect of a greater MeDi adherence on cognitive health, including a reduced risk of Alzheimers disease and cognitive impairment. Since then, six additional studies, from longitudinal cohorts or post-hoc analyses of randomized controlled trials conducted in the USA and Europe, have been published and provided mixed results. Potential reasons for such discrepancies include methodological limitations inherent to observational studies, and interactions between diet, environmental factors, such as those enhancing cognitive reserve, chronic diseases, and genetic factors. SummaryOverall, available evidence suggests that the MeDi might exert a long-term beneficial effect on brain functioning. However, more high-powered observational studies with long-term follow-up for cognition and randomized controlled trials assessing the impact of shifting to a MeDi on cognitive functions are still needed in various populations.

Omega-3 fatty acids and cognitive decline: modulation by ApoEε4 allele and depression

Long-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may slow cognitive decline. The ε4 allele of the ApolipoproteinE (ApoE), the main genetic risk factor for Alzheimers disease, and depressive symptoms, which are frequently associated with cognitive impairment in older persons, may modify this relationship. We estimated the associations between EPA and DHA plasma levels and subsequent cognitive decline over 7 years, taking into account ApoE-ε4 status and depressive symptoms, in a prospective population-based cohort. Participants (≥ 65 years, n = 1,228 nondemented at baseline) were evaluated at least once over three follow-up visits using four cognitive tests. Plasma EPA was associated with slower decline on Benton Visual Retention Test (BVRT) performances in ApoE-ε4 carriers, or in subjects with high depressive symptoms at baseline. Plasma DHA was associated with slower decline on BVRT performances in ApoE-ε4 carriers only. EPA and DHA may contribute to delaying decline in visual working memory in ApoE-ε4 carriers. In older depressed subjects, EPA, but not DHA, may slow cognitive decline.