Higher Mediterranean- DASH for Neurodegenerative Delay (MIND) diet scores have previously been associated with larger total brain volume (TBV) in the Framingham Offspring Study (FOS) community-based cohort. We investigated cross-sectional relationships between the MIND diet and structural brain imaging volumes and white matter hyperintensity volume (WMHV) across six community-based cohorts. We analyzed data from 3130 dementia-, stroke- and other neurological disease free adults (aged 65 to 74) who participated in the Atherosclerosis Risk in Communities (ARIC) cohort, Cardiovascular Health Study (CHS), Three City (3C) cohort, FOS cohort, Rotterdam Study (RS) or the Study of Health in Pomerania (SHIP) cohort. Individuals completed a brain magnetic resonance imaging (MRI) scan, and a validated food frequency questionnaire (FFQ) (ARIC, CHS, FOS, RS), 24h dietary recall (3C), or an extensive food list (SHIP). The MIND diet consists of ten healthy (e.g. green leafy vegetables, berries and fish) and five unhealthy (e.g. cheese, red meat and products and fast fried foods) components. Outcomes from brain MRI included TBV, total grey matter volume (TGMV), hippocampal volume (HPV), and WMHV. We used multivariable linear regression to relate MIND diet adherence to the outcomes. Results were combined in meta-analysis using fixed effects and random effects models. Higher MIND diet scores (score range: 0-15) were associated with larger HPV (beta = 0.015, 95% confidence interval = 0.004 to 0.026, cm³ per one unit MIND diet score increase) after adjustment for age, age squared, sex, time from clinical exam to brain MRI exam, total intracranial volume and energy intake, but not with TBV, TGMV and WMHV. Heterogeneity between studies was low (I 2 = 0% TBV, TGMV, HPV) to moderate (I 2 = 44% WMHV). In cross-sectional analyses, higher MIND diet scores were associated with larger HPV, but not with other brain volume measures. It might be that HPV was a more sensitive marker of brain health in the populations under study. Future studies are encouraged to examine the associations between the MIND diet and amyloid and tau positron emission tomography (PET) imaging to elucidate whether a relationship between the MIND diet and dementia pathologies exists.

Findings from observational studies which examined relationships between Mediterranean- DASH for Neurodegenerative Delay(MIND) diet scores and risk of dementia are promising. We investigated whether MIND diet scores are associated with incident all-cause dementia and being alive and dementia free at age 80 across six community-based cohorts. We analyzed data from 8714 dementia free adults (mean age range across cohorts: 67 to 73) who participated in the Atherosclerosis Risk in Communities (ARIC) cohort, Cardiovascular Health Study (CHS), Three City (3C) cohort, Framingham Offspring Study (FOS) cohort, Rotterdam Study (RS) or the Study of Health in Pomerania (SHIP) cohort. Individuals had incident all-cause dementia surveillance data available and completed a validated food frequency questionnaire (FFQ) (ARIC, CHS, FOS, RS, 3C), 24h dietary recall (3C), or an extensive food list (SHIP). The MIND diet score is derived from ten healthy and five unhealthy components. We used Cox regression and logistic regression. Results were combined in meta-analysis using fixed effects and random effects models. Higher MIND diet scores (score range: 0-15) and MIND diet scores ≥6 were associated with decreased risk for all-cause dementia (Hazard ratio(HR) = 0.96,95% confidence interval(CI)=0.93-0.99; 0.86,95%CI=0.78-0.94, respectively) after adjustment for age at dietary intake assessment visit, sex, and total energy intake. Further, higher MIND diet scores and MIND diet scores ≥6 related to higher odds of being alive and dementia free at age 80 (Odds ratio(OR) = 1.11,95%CI=1.07-1.15;OR=1.37,95%CI=1.22-1.54, respectively). Heterogeneity between studies ranged between 0-30%. Higher MIND diet scores associated with decreased all-cause dementia risk and being alive and dementia free at age 80. We encourage clinical trials to examine the MIND diet in relation to dementia related outcomes such as amyloid and tau to elucidate whether a causal relationship between the MIND diet and dementia pathologies exists.

Racial and ethnic disparities in healthy aging represent an emerging public health crisis that will only grow worse as our population grows older. Healthy lifestyle behaviors are proposed as a key strategy to promote healthy aging. However, the potential of lifestyle interventions to address aging health disparities is uncertain. We analyzed data from 42 625 adult participants (aged 20-85 years) participating in National Health and Nutrition Examination Survey (NHANES), 1999-2018 to evaluate relationships among healthy lifestyle behaviors and biological aging across White, Black, and Hispanic-identifying groups. We measured healthy lifestyle as adherence to a Mediterranean diet and level of leisure-time physical activity using established methods. We measured healthy aging using the PhenoAge biological age algorithm applied to blood chemistry data. We tested associations within each race/ethnic identity group and compared associations across groups using regression models with interaction terms. We found that within each race/ethnic identity group, greater adherence to a Mediterranean diet and higher levels of leisure-time physical activity were associated with younger biological age, independent of demographic and socioeconomic confounders, obesity, and smoking. However, these associations were stronger among White- as compared to non-Hispanic Black- and Hispanic-identifying adults. Results suggest that healthy lifestyle factors are likely to promote healthy aging across the population. However, lifestyle factors alone may not be sufficient to completely address race/ethnic disparities in healthy aging. Future studies will need to investigate additional ways to reduce racial and ethnic disparities in healthy aging.

OBJECTIVE:To determine if circulating markers of inflammation are associated with cognitive decline in older adults. BACKGROUND:Inflammation has been shown to play a major role in the development of dementia and cognitive aging in general. Studies have focused on major biomarkers of inflammation such as C-Reactive Protein (CRP), Interleukin-6 (IL-6) or Tumor Necrosis Factor-a (TNF-a). In the present study, we explored inflammatory profiles as the combination of 23 cytokine biomarkers, and their associations with cognitive decline. DESIGN/METHODS:We included 1,483 non-demented participants (≥65 years-old) from the 2009 cohort of Washington Heights-Inwood Community Aging Project (WHICAP). Inflammatory profiles were identified from Principal Component Analysis (PCA) on 23 blood cytokines biomarkers. Repeated cognitive assessments, performed every 18 to 24 months for up to 12.5 years, were used to assess cognitive decline in 4 cognitive domains (memory, language, executive speed, and visuospatial functions) and in global cognition. RESULTS:The second PCA component identified an inflammatory profile characterized by negative loadings for anti-inflammatory cytokines (e.g., IL-3, IL-4, IL-10) and positive loadings for pro-inflammatory cytokines, such as MIP-1β and TNF-a. A higher score of this component, indicating more pro-inflammatory profile, and higher levels of its key drivers (MIP-1β and TNF-a) were associated with lower baseline cognitive performances for global cognition and executive speed, after adjustment for age, sex, race/ethnicity and ApoE-ɛ4. No association of PCA components with cognitive decline was observed in longitudinal analysis. However, VEGF and CRP were associated with a faster decline in global cognition. Additional adjustments on vascular risk factors only slightly attenuated the association. CONCLUSIONS:Among older adults, a pro-inflammatory immune profile is associated with lower baseline cognitive performances, and some individual pro-inflammatory cytokines might be associated with faster cognitive decline. Disclosure: Dr. Thomas has nothing to disclose. Ms. Sanchez has nothing to disclose. Mrs. Reyes-Dumeyer has nothing to disclose. Dr. Mayeux has nothing to disclose. The institution of Dr. Gu has received research support from NIH.

AbstractAmong food groups with putative benefits for brain structures, dairy products (DP) have been poorly studied. The sample included participants without dementia from the ancillary brain imaging study of the Three-City cohort who were aged 65+ years, had their DP intake assessed with a FFQ at baseline and underwent an anatomical scan 3 years (n 343) or 9 years (n 195) after completing the dietary survey. The frequencies of consumption of total DP, milk and cheese were not associated with brain structure. Compared with the lowest frequency, the highest frequency of fresh DP (F-DP) consumption (< 0·5 v. > 1·5 times/d) was significantly associated with a lower medial temporal lobe volume (MTLV) (β = −1·09 cm3, 95 % CI − 1·83, −0·36) 9 years later. In this population-based study of older adults, the consumption of F-DP more than 1·5 times/d was associated with a lower MTLV, which is considered an early biomarker of Alzheimer’s disease, 9 years later. This original study should be replicated in different settings before conclusions are drawn.

Substantial evidence supports the benefice of healthy diet for brain aging; however, the underlying pathways remain largely unknown. Leveraging a unique cohort design with assessment of long-term dietary habits, DNA methylation data, and 10-year follow-up for dementia, we evaluated the mediating role of pace of biological aging on the relationship of diet with dementia. We investigated the specificity of this pathway for brain aging, as compared to overall aging, by investigating the same mediation for the risk of all-cause mortality. We included 1,644 participants (≥60 years-old) from the Framingham Offspring Cohort, who were free of dementia at baseline examination (exam 8 [2005-2008]). We evaluated long-term adherence to a Mediterranean diet (MeDi) by averaging dietary scores across four assessments (validated food frequency questionnaire at exams 5 [1991-1995], 6 [1995-1998], 7 [1998-2001], and 8). Using DNA methylation data collected at baseline, we measured the pace of biological aging through the DunedinPACE epigenetic clock, which was the DNA methylation measure the most strongly associated with dementia in prior studies. Incidence of dementia and mortality was adjudicated from baseline until 2018 by expert committees. We performed mediation analyses to estimate the role of pace of biological aging on the relationship between diet and dementia or all-cause mortality. Over the follow-up (maximum, 13.8 years), 140 (8.5%) participants developed dementia, and 471 (28.6%) died. Participants with a higher adherence to MeDi had a slower pace of biological aging, and lower risks of dementia and of all-cause mortality ( Figure ). A faster pace of aging was associated with increased risks of dementia and mortality. Biological aging mediated 13% [95% CI, 0.06; 0.43] of the association between diet and dementia, and 43% [0.23; 1.08] of the association of diet with mortality. Part of the association of healthier diet with lower risk of dementia is mediated by a slowing of global processes of biological aging. However, this pathway does not fully explain the association of diet and dementia and the proportion mediated was three times smaller than what was observed for mortality, suggesting that other mechanisms, especially brain-specific mechanisms, need to be further described.

Environmental factors, such as nutrition, influence brain physiology and health throughout the life course. While research has focused on the extremes of the age spectrum, less is known about early adulthood, yet a critical period for the consolidation of brain maturation and the building of adult behaviors. Nutrition may impact late maturational changes in the post-adolescent brain and contribute to the degree of brain reserve that minimizes the risk to develop dementia. We took advantage of a large sample of young adults to evaluate the association of dietary behavior with brain structure characteristics. This cross-sectional study included 1721 university students (18-35 years-old) from the French i-Share cohort, who underwent brain MRI. A 12-item online Food Frequency Questionnaire was used to evaluate consumption in major food groups and to determine dietary patterns from Principal Component Analysis (PCA). Multivariable-adjusted linear regressions were used to estimate the association of PCA scores with brain structure (cortical thickness and surface area, grey matter and white matter volumes, diffusion parameters). The first PCA component (explained variance, 17%) contrasted a healthy diet (higher fruit and vegetable intakes) to a poor diet (higher fast food, sugary drink and snack consumptions). In models adjusted for total intracranial volume, age, sex, physical activity, body mass index, alcohol and tobacco consumptions, a higher PCA score (reflecting healthier diet) was associated with lower total gray matter volume (β for 1 point score = –0.17 [95%CI, –0.31; –0.03] cm 3 ), in various brain areas ( Figure ). Healthy diet was also associated with lower global white matter volume (β = –0.18 [–0.32; –0.03] cm 3 ). No association was found with diffusion tensor imaging, and neurite orientation dispersion and density imaging metrics in the white matter. In this large sample of young adults, healthier diet was associated with lower brain volumes, independent of multiple potential confounders. Gray matter volume loss during post-adolescence is a marker of brain maturation; thus, environmental factors emphasizing this loss may benefit maturation. Our results raise the hypothesis that a healthy diet may favor and a poor diet may hamper brain maturation; an assumption which deserves further investigation in other populations.

Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, which combines higher consumption of vegetables, berries, nuts, whole grains, olive oil, fish, beans and poultry, with lower consumption of meat, sugars and saturated fats, is a promising strategy to prevent dementia. However, evidence in populations with non-US food culture, especially from Europe, is limited. OBJECTIVES: To evaluate the association of a French-adapted MIND diet score with gray matter volumes, white matter microstructure and incident dementia. This longitudinal study included participants from the population-based Three-City Bordeaux cohort (≥65 years), with a follow-up from June 2001 to February 2018. Dementia-free participants at dietary assessment, in 2001–2002, who underwent systematic detection of incident dementia (over up to 7 visits). A subset of the cohort was included in an ancillary MRI study in 2010–2011. A French-adapted MIND diet score (range, 0–15) was computed from a 148-item Food Frequency Questionnaire and a 24-hour recall administered at home. Incident dementia and its subtypes were adjudicated by an expert committee; and gray matter volumes and white matter microstructure were assessed by 3D-T1 MRI and diffusion-MRI. RESULTS: Among 1,412 participants (mean age, 75.8 [SD, 4.8]; 63

We are grateful for the comments on our research.1 We investigated the association of fish intake and MRI burden of cerebrovascular disease. We agree with Dr. Brenner that other dietary components, including meat, may affect brain vascular health.2 In our study, we focused on the beneficial effects of fish intake as a primary source of long-chain omega-3 polyunsaturated fatty acids. To account for the potential confounding effect of other dietary components, our models were adjusted for the intake of meat, fruits, vegetables, legumes, and olive oil. For example, higher red meat intake may be associated with lower fish intake, and related to increasing vascular disease. Adjusting for potential confounding factors allows the estimation of the association between the exposure of interest (fish intake) and the outcome (cerebrovascular burden), with all other variables having a constant value. Thus, we believe that it is unlikely that the observed adjusted associations of fish intake to lower cerebrovascular disease burden are confounded by decreased exposure to glycolylneuraminic acid from meat. Investigating the association of glycolylneuraminic acid with brain vascular health would certainly require a dedicated study.

Purpose of review Nutrition is a complex exposure (i.e., the food exposome) that influences brain function and health through multiple pathways. We review recent epidemiological studies that have improved the characterization of the food exposome and brain health in humans and have revealed promising nutrition-based strategies to prevent cognitive aging. Recent findings A selection of epidemiological research from the past 18 months of both observational and clinical studies is presented, with a focus on novel findings, including novel nutrient and diet patterns, diet-related approaches to rescue brain energetics defects in aging, and biomarker-based studies to decipher specific neurobiological pathways of nutrition and brain health. Summary Although healthy diets such as the Mediterranean diet promote brain health throughout life, specific diets, such as the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay diet, or specific nutrients (LC n-3 polyunsaturated fatty acids, carotenoids, vitamin D, B vitamins, polyphenols) alone or in combination, may prevent cognitive aging. Diet management approaches to rescue brain energetics defects such as the Modified Mediterranean-ketogenic diet may be promising to prevent neurodegenerative diseases. Expanding research also suggests that promotion of a healthy gut microbiome through prebiotic foods may preserve the diet–gut–brain axis with aging. Future studies should explore more individualized preventive approaches through a ’precision nutrition’ framework.

Background: Low blood status in several nutritional compounds, including long-chain omega-3 fatty acids (LC n-3 PUFA), carotenoids, and vitamin D, have been associated with a higher risk to develop dementia. Nutritional deficiencies may potentiate each other regarding dementia risk; yet the association of multiple nutritional deficiencies with dementia has been little explored. Objective: To develop an index of micronutritional biological status (MNBS) for the screening of multi-micronutritional deficiencies associated with the risk of dementia in a prospective population-based cohort of older persons. Methods: We included participants from the Bordeaux Three-City study, who were free of dementia at baseline, had blood measurements of LC n-3 PUFA, carotenoids, and 25(OH)D, and who were followed for up to 18 years for dementia. We used penalized splines in Cox models to model dose-response relationships of each nutritional component with the risk of dementia and construct a risk index. Results: 629 participants with an average age of 73.1 years were included in the study. Each increase of 1 SD of the MNBS index was associated with a 46% higher risk of dementia (HR = 1.46, 95% CI 1.23; 1.73). Participants with highest index ([mean+1SD; max]) had a 4-fold increased risk of dementia compared with participants with a low index ([min; mean-1SD]) (HR = 4.17, 95% CI 2.30; 7.57). Conclusion: This index of assessment of micronutritional biological status is a practical tool that may help identify populations with inadequate nutritional status, screen eligible individuals for nutritional prevention in primary care, or for supplementation in preventive trials of dementia.

Cerebrovascular disease (CVD), a major contributor of cognitive aging, is characterized by subclinical damage visualized on brain MRI, including covert brain infarcts, white matter hyperintensities (WMH) and dilated perivascular spaces (dPVS). Few protective factors for brain vascular health, that may help prevent stroke and dementia, have been identified so far. Fish intake may prevent ischemic events and small vessel disease. When investigating factors with a pleiotropic effect such as fish, there is interest to capture pathophysiological burden globally, combining biomarkers into a single metric. Here, we investigated the association of fish intake with a global indicator of the MRI burden of CVD among older adults. This Three-City Dijon study included 1,623 participants (≥65 years) without history of dementia, stroke or cardiovascular disease, who had completed a Food Frequency Questionnaire and underwent brain MRI with automated assessment of WMH, visual detection of covert infarcts, and grading of dPVS. A global indicator of CVD burden was estimated using a factorial analysis of mixed data; association of fish intake with the indicator was assessed by adjusted linear regression. The proportions of participants consuming fish less than once a week, once a week, 2 to 3 times and more than 4 times per week were 11%, 37%, 47% and 6%, respectively. The continuous CVD burden indicator, derived from the first dimension of the factorial analysis (32.4% of explained variance), was associated with a higher WMH load, more infarcts and higher dPVS severity. Higher fish intake was associated with a lower CVD burden indicator ( P for trend <0.001). Compared to participants consuming fish less than once a week, the CVD indicator decreased by -0.19 units (95% CI, -0.37; -0.005) for those consuming fish 2-3 times per week and by -0.31 units (-0.59; -0.03) for ≥4 times per week. These effect estimates of eating fish at least twice a week were equivalent to having a 4 to 5 years younger brain in terms of vascular health (β = 0.05 units (0.03; 0.06) for each one year increase of age). Fish consumption may promote brain vascular health before manifestation of overt brain disease.

The MIND diet score for brain health is a 15-item score combining neuroprotective dietary components (e.g. green leafy vegetables, nuts, berries, whole grains, fish). A higher MIND diet score was associated with slower cognitive decline and lower risk of Alzheimer’s disease; however, its relationship with brain structure has not yet been investigated. Taking advantage of a large population-based cohort of older adults, we constructed a MIND diet score adapted to French dietary habits and we evaluated the associations of the score with the risk of dementia and Alzheimer’s disease (AD). In a secondary analysis, we investigated the cross-sectional relationship between the MIND diet score and gray matter structure assessed by Magnetic Resonance Imaging (MRI). We included 1,412 dementia-free participants (aged ≥65) from the Three-City Bordeaux study. A 148-item Food Frequency Questionnaire and a 24-hour recall administered at home in 2001-2002 were used to calculate a MIND diet score, adapting component thresholding to French habits and guidelines (when applicable). Incidence of dementia and its subtypes from 2001-2002 until 2017-2018 was adjudicated by an expert committee. A subset of 207 participants were included in an ancillary MRI study in 2010-2011. Gray matter volume and cortical thickness within the cortical signature of AD (i.e., 9 regions with cortical thickening predictive of subsequent AD) were estimated using FreeSurfer 5.1. Over a median follow-up of 9.7 years (maximum 16.3 years), 356 participants (25.2%) were diagnosed with dementia, including 240 participants (17.0%) with AD. In multivariable Cox models, a higher MIND diet score was associated with lower risks of dementia (Hazard Ratio [HR] = 0.89 for each 1-point increase of score; 95% Confidence Intervals [CI] = 0.83-0.95) and AD (HR = 0.88; 95% CI = 0.81-0.96). In the MRI sub-study, a higher MIND diet score was significantly associated with higher total grey matter volume (β=2.54 mm 3 for 1 point of score, p=0.005) and greater thickness in the AD signature (β=0.02 mm for 1 point of score, p<0.001). This large population-based study provides further evidence and new mechanistic insights for the role of the MIND diet in the prevention of dementia and AD.

Background and Objectives Fish intake may prevent cerebrovascular disease (CVD), yet the mechanisms are unclear, especially regarding its impact on subclinical damage. Assuming that fish may have pleiotropic effect on cerebrovascular health, we investigated the association of fish intake with global CVD burden based on brain MRI markers. Methods This cross-sectional analysis included participants from the Three-City Dijon population-based cohort (age >= 65 years) without dementia, stroke, or history of hospitalized cardiovascular disease who underwent brain MRI with automated assessment of white matter hyperintensities, visual detection of covert infarcts, and grading of dilated perivascular spaces. Fish intake was assessed through a frequency questionnaire, and the primary outcome measure was defined as the first component of a factor analysis of mixed data applied to MRI markers. The association of fish intake with the CVD burden indicator was studied with linear regressions. Results In total, 1,623 participants (mean age 72.3 years, 63% women) were included. The first component of factor analysis (32.4% of explained variance) was associated with higher levels of all 3 MRI markers. Higher fish intake was associated with lower CVD burden. In a model adjusted for total intracranial volume, compared to participants consuming fish <1 time per week, those consuming fish 2 to 3 and >= 4 times per week had a beta = -0.19 (95% confidence interval -0.37 to -0.01) and beta = -0.30 (-0.57 to -0.03) lower indicator of CVD burden, respectively (p trend < 0.001). We found evidence of effect modification by age such that the association of fish to CVD was stronger in younger participants (65-69 years) and not significant in participants >= 75 years of age. For comparison, in the younger age group, consuming fish 2 to 3 times a week was roughly equivalent (in the opposite direction) to the effect of hypertension. Discussion In this large population-based study, higher frequency of fish intake was associated with lower CVD burden, especially among participants <75 years of age, suggesting a beneficial effect on brain vascular health before manifestation of overt brain disease. Classification of Evidence This study provides Class II evidence that in individuals without stroke or dementia, higher fish intake is associated with lower subclinical CVD on MRI.

Une consommation élevée de poisson, source d’acides gras omega-3 à longue chaîne, a été associée à un moindre risque d’accident vasculaire cérébral, de démence et de déclin cognitif. Toutefois, les résultats épidémiologiques ne permettent pas d’inférer de façon univoque un nombre de portions par semaine à recommander pour la prévention. Le vieillissement cognitif résulte en partie d’une détérioration de la santé vasculaire cérébrale. En dehors des accidents vasculaires cérébraux manifestes, il existe des dommages cérébrovasculaires cachés qui font le lit de la démence, et qui pourraient être particulièrement sensibles aux bénéfices du poisson. La pathologie cérébrovasculaire infraclinique peut être caractérisée à l’imagerie par résonance magnétique (IRM) par la présence d’hypersignaux de la substance blanche (HSB), d’infarctus lacunaires ou encore une dilatation des espaces périvasculaires. Très peu d’études ont analysé la relation entre la consommation de poisson ou en omega-3 et ces marqueurs à l’IRM, et aucune n’a modélisé le fardeau cérébrovasculaire (FCV) dans son ensemble. Ainsi, l’objectif de cette étude était d’évaluer l’association transversale entre la consommation de poisson et le FCV infraclinique global chez le sujet âgé, dans la cohorte des 3-Cités Dijon. Au total, 1667 sujets non-déments et sans antécédent de maladies vasculaires cliniques ont répondu à un bref fréquentiel alimentaire et ont passé un examen IRM, à l’inclusion en 1999–2000. La charge en HSB ( % de la substance blanche), la présence d’infarctus lacunaires (oui/non) et la sévérité de la dilatation des espaces périvasculaires (3 degrés de sévérité) ont été évalués à l’IRM. Un indicateur du FCV global combinant ces trois marqueurs a été calculé par analyse factorielle de données mixtes (32,6 % de variance expliquée par la première dimension). L’association entre la consommation de poisson et l’indicateur FCV a été évaluée par régression linéaire ajustée sur l’âge, le sexe, le niveau d’études, le génotype APOE-ɛ4, le volume intracrânien total, les facteurs de risques cardiovasculaires et les autres habitudes alimentaires. Parmi les participants inclus (âge moyen = 72,3 [± 4,1] ans), 10,7 % consommaient du poisson < 1 fois/semaine, 36,8 % 1 fois/semaine, 46,7 % 2 à 3 fois/semaine et 5,8 % ≥ 4 fois/semaine. L’indicateur FCV défini par la première dimension de l’analyse factorielle contrastait les sujets avec un faible fardeau (charge en HSB faible, pas d’infarctus et dilation des espaces périvasculaires de faible sévérité) des sujets avec un fardeau important. Dans les modèles multivariés, les participants consommant plus de poisson avaient un moindre FCV comparé à ceux en consommant < 1 fois/semaine (rapport de Cotes [IC95 %] = −0,20 [−0,38 ; −0,02] pour 2–3 fois/semaine ; et −0,27 [−0,54 ; −0,01] pour ≥ 4 fois/semaine). Aucune autre composante alimentaire (fruits, légumes, légumineuses, viande, huile d’olive) n’était significativement associée. Dans cette grande cohorte de sujets âgés, la consommation de poisson était linéairement associée à un moindre fardeau cérébrovasculaire infraclinique. Ces résultats suggèrent un rôle bénéfique du poisson pour la préservation de la santé cérébrovasculaire avec le vieillissement.

Les acides gras polyinsaturés oméga-3 (AGPI n-3) à longue chaîne, en particulier les acides eicosapentaénoïque (EPA) et docosahexaénoïque (DHA), sont des constituants importants des membranes neuronales. Les études épidémiologiques ont mis en évidence des associations entre la consommation ou le statut biologique en AGPI n-3 et un moindre risque de démence et d’évènements associés (déclin cognitif, atrophie cérébrale). Toutefois, des résultats contradictoires ont été observés selon l’AGPI n-3 considéré (AGPI n-3 totaux ou EPA + DHA versus EPA ou DHA) et la source d’exposition (consommation versus statut sanguin) et les études antérieures ont porté sur un temps de suivi relativement court (souvent inférieur à 5 ans). L’objectif de cette étude observationnelle était de s’appuyer sur le long suivi d’une cohorte populationnelle de sujets âgés, la cohorte des 3-Cités (3 C), pour évaluer les associations entre le statut sanguin en AGPI n-3 et l’évolution au long cours de trois évènements complémentaires : l’incidence de la démence, le déclin cognitif et l’atrophie du lobe temporal médian (LTM, un biomarqueur de la démence). Dans la cohorte 3C-Bordeaux (âge ≥ 65 ans), 1279 sujets initialement non-déments ont eu des mesures plasmatiques d’AGPI n-3 à l’inclusion. Des tests cognitifs réalisés à l’inclusion et aux différentes visites de suivi (7 suivis, durée maximum : 17 ans) ont permis l’évaluation du déclin cognitif global (n = 1185) et du déclin de la mémoire (n = 1039). Une étude ancillaire avec des examens répétés en Imagerie par Résonance Magnétique (IRM) (3 examens, durée maximum de suivi : 10 ans) a permis l’évaluation de l’atrophie du LTM (n = 467). Des modèles conjoints ajustés ont été utilisés pour évaluer les associations entre EPA + DHA et les trajectoires d’évolution de la cognition globale, de la mémoire et des volumes du LTM en tenant compte de la sortie d’étude. L’association entre les taux plasmatiques en EPA + DHA et le risque de démence sur 14 ans a été étudiée par modèle de Cox multivariable. Des taux plasmatiques en EPA + DHA plus élevés étaient significativement associés à un moindre risque de démence (HR pour 1 écart-type = 0,87 ; IC95 % = [0,79–0,98]), à un moindre déclin des performances cognitives globales et de la mémoire (p = 0,04 et 0,06 pour chacune des deux pentes respectivement) et à une moindre atrophie du LTM (p = 0,02 pour la pente). La concordance des associations trouvées entre les taux plasmatiques en EPA + DHA et les trois évènements d’intérêt en lien avec la démence, sur un long temps de suivi, apporte des arguments supplémentaires en faveur d’un rôle bénéfique des AGPI n-3 pour la prévention de la démence et du déclin cognitif.

Carotenoids are vegetable pigments uniquely provided by diet which have antioxidant, immunomodulatory and specific neuroprotective properties. Carotenes (found in orange‐yellow fruits and vegetables) are precursors of retinoids, key signaling molecules for synaptic plasticity. The xanthophylls, lutein and zeaxanthin (found in green vegetables, orange‐yellow fruits and corn) cross the blood‐brain barrier, may decrease lipid peroxidation and stabilize lipid‐protein structures in neuronal membranes. Limited epidemiological studies on dietary carotenoids (assessed by questionnaires) reported inconsistent associations with brain aging using cognitive change as an outcome (and not neuroimaging or clinical dementia or Alzheimer’s disease diagnosis). However, blood carotenoids levels were associated with lower risk of dementia over 10 years, in a large cohort of older adults, the Three‐City (3C) study. Here, we further investigated whether blood carotenoids were also associated with the 10‐year atrophy of the medial temporal lobe (MTL), a central biomarker of neurodegeneration in aging.

Long‐chain omega‐3 polyunsaturated fatty acids (n‐3 PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mainly provided together by fish intake in the human diet, are important constituents of neural membranes. Epidemiological studies reported associations between long‐chain n‐3 PUFA intakes or blood concentrations, and lower risks of dementia and related outcomes (cognitive decline, brain atrophy). However, evidence has been inconsistent according to the type (e.g., EPA, DHA or total n‐3 PUFA) and/or the exposures (intake versus blood status) investigated. Moreover, previous studies displayed short follow‐up periods (generally less than 5 years). In this study, we took advantage of the long follow‐up for dementia and related outcomes in a large cohort of older persons, the Three‐City (3C) study, to look for robust associations of an omega‐3 index in plasma (EPA+DHA), with the long‐term evolution of three complementary outcomes: atrophy of the medial temporal lobe (MTL, a biomarker of dementia), cognitive decline and incidence of dementia.

INTRODUCTION:We searched for consistent associations of an omega-3 index in plasma (sum of eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) with several dementia-related outcomes in a large cohort of older adults.METHODS:We included 1279 participants from the Three-City study, non-demented at the time of blood measurements at baseline, with face-to-face neuropsychological assessment and systematic detection of incident dementia over a 17-year follow-up. An ancillary study included 467 participants with up to three repeated brain imaging exams over 10 years.RESULTS:In multivariable models, higher levels of plasma EPA+DHA were consistently associated with a lower risk of dementia (hazard ratio for 1 standard deviation = 0.87 [95% confidence interval, 0.76-0.98]), and a lower decline in global cognition (P = .04 for change over time), memory (P = .06), and medial temporal lobe volume (P = .02).DISCUSSION:This prospective study provides compelling evidence for a relationship between long-chain omega-3 fatty acids levels and lower risks for dementia and related outcomes.