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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.

The role of nutrition has been investigated for decades under the assumption of one-size-fits-all. Yet there is heterogeneity in metabolic and neurobiological responses to diet. Thus a more personalized approach may better fit biological reality and have increased efficacy to prevent dementia. Personalized nutrition builds on the food exposome, defined as the history of diet-related exposures over the lifetime, and on its interactions with the genome and other biological characteristics (eg, metabolism, the microbiome) to shape health. We review current advances of personalized nutrition in dementia research. We discuss key questions, success milestones, and future roadmap from observational epidemiology to clinical studies through basic science. A personalized nutrition approach based on the best prescription for the most appropriate target population in the most relevant time-window has the potential to strengthen dementia-prevention efforts.

The gut microbiome is involved in nutrient metabolism and produces metabolites that, via the gut–brain axis, signal to the brain and influence cognition. Human studies have so far had limited success in identifying early metabolic alterations linked to cognitive aging, likely due to limitations in metabolite coverage or follow-ups. Older persons from the Three-City population-based cohort who had not been diagnosed with dementia at the time of blood sampling were included, and repeated measures of cognition over 12 subsequent years were collected. Using a targeted metabolomics platform, we identified 72 circulating gut-derived metabolites in a case–control study on cognitive decline, nested within the cohort (discovery n = 418; validation n = 420). Higher serum levels of propionic acid, a short-chain fatty acid, were associated with increased odds of cognitive decline (OR for 1 SD = 1.40 (95% CI 1.11, 1.75) for discovery and 1.26 (1.02, 1.55) for validation). Additional analyses suggested mediation by hypercholesterolemia and diabetes. Propionic acid strongly correlated with blood glucose (r = 0.79) and with intakes of meat and cheese (r > 0.15), but not fiber (r = 0.04), suggesting a minor role of prebiotic foods per se, but a possible link to processed foods, in which propionic acid is a common preservative. The adverse impact of propionic acid on metabolism and cognition deserves further investigation.

Background Vitamin D is critical to brain health and a promising candidate to prevent cognitive decline and onset of Alzheimer disease (AD), although the underlying brain mechanisms are unclear. Objectives This study aimed to determine the association between vitamin D intake and brain cortical thickness in older adults. Methods This was a cross-sectional investigation of 263 cognitively unimpaired participants, aged 65 y and older, participating in the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) trial (an ongoing study testing the effects of a 3-y diet intervention on cognitive decline). Vitamin D intake, from diet and supplements, was ascertained from an FFQ. Linear regression analysis, adjusted for age, sex, race, education, income, cognitive and physical activities, and cardiovascular disease risk factors, was used to determine the association between vitamin D intake and cortical thickness of the whole brain, lobes, and AD signature. Results Total vitamin D intake was associated with cortical thickness of the temporal lobe and AD signature. Compared with individuals in the lowest quartile of total vitamin D intake [median: 140 international units (IU)/d], those in the highest quartile (median: 1439 IU/d) had a 0.038-mm (95% CI: 0.006, 0.069 mm) thicker temporal lobe and 0.041-mm (95% CI: 0.012, 0.070 mm) thicker AD signature. Most vitamin D intake was from supplements, and supplemental intake was also associated with cortical thickness. Compared with those who used no supplement, individuals taking 800-1000 IU/d and >1000 IU/d of supplemental vitamin D had a 0.039-mm (95% CI: 0.013, 0.066 mm) and 0.047-mm (95% CI: 0.013, 0.081 mm) thicker temporal lobe and a 0.037-mm (95% CI: 0.013, 0.061 mm) and 0.046-mm (95% CI: 0.015, 0.077 mm) thicker AD signature, respectively. Dietary vitamin D was not related to brain cortical thickness in our sample. Conclusions In cognitively unimpaired older adults, total and supplemental vitamin D intakes were associated with cortical thickness in regions vulnerable to AD.This trial was registered at clinicaltrials.gov as NCT02817074.

International audience; Introduction: Diet and exercise influence the risk of cognitive decline (CD) and dementia through the food metabolome and exercise-triggered endogenous factors, which use the blood as a vehicle to communicate with the brain. These factors might act in concert with hippocampal neurogenesis (HN) to shape CD and dementia.Methods: Using an in vitro neurogenesis assay, we examined the effects of serum samples from a longitudinal cohort (n = 418) on proxy HN readouts and their association with future CD and dementia across a 12-year period.Results: Altered apoptosis and reduced hippocampal progenitor cell integrity were associated with exercise and diet and predicted subsequent CD and dementia. The effects of exercise and diet on CD specifically were mediated by apoptosis.Discussion: Diet and exercise might influence neurogenesis long before the onset of CD and dementia. Alterations in HN could signify the start of the pathological process and potentially represent biomarkers for CD and dementia.

ObjectiveTo use network science to model complex diet relationships a decade before onset of dementia in a large French cohort, the 3-City Bordeaux study.MethodsWe identified cases of dementia incident to the baseline food frequency questionnaire over 12 years of follow-up. For each case, we randomly selected 2 controls among individuals at risk at the age at case diagnosis and matched for age at diet assessment, sex, education, and season of the survey. We inferred food networks in both cases and controls using mutual information, a measure to detect nonlinear associations, and compared food consumption patterns between groups.ResultsIn the nested case-control study, the mean (SD) duration of follow-up and number of visits were 5.0 (2.5) vs 4.9 (2.6) years and 4.1 (1.0) vs 4.4 (0.9) for cases (n = 209) vs controls (n = 418), respectively. While there were few differences in simple, average food intakes, food networks differed substantially between cases and controls. The network in cases was focused and characterized by charcuterie as the main hub, with connections to foods typical of French southwestern diet and snack foods. In contrast, the network of controls included several disconnected subnetworks reflecting diverse and healthier food choices.ConclusionHow foods are consumed (and not only the quantity consumed) may be important for dementia prevention. Differences in predementia diet networks, suggesting worse eating habits toward charcuterie and snacking, were evident years before diagnosis in this cohort. Network methods, which are designed to model complex systems, may advance our understanding of risk factors for dementia.

SCOPE: Diet is considered an important modulator of cognitive decline and dementia, but the available evidence is, however, still fragmented and often inconsistent.METHODS AND RESULTS: The article studies the long-term prospective Three-City Cohort, which consists of two separate nested case-control sample sets from different geographic regions (Bordeaux, n = 418; Dijon, n = 424). Cognitive decline is evaluated through five neuropsychological tests (Mini-Mental State Examination, Benton Visual Retention Test, Isaac's Set Test, Trail-Making Test part A, and Trail-Making Test part B). The food-related and microbiota-derived circulating metabolome is studied in participants free of dementia at baseline, by subjecting serum samples to large-scale quantitative metabolomics analysis. A protective association is found between metabolites derived from cocoa, coffee, mushrooms, red wine, the microbial metabolism of polyphenol-rich foods, and cognitive decline, as well as a negative association with metabolites related to unhealthy dietary components, such as artificial sweeteners and alcohol.CONCLUSION: These results provide insight into the early metabolic events that are associated with the later risk to develop cognitive decline within the crosstalk between diet, gut microbiota and the endogenous metabolism, which can help identify potential targets for preventive and therapeutic strategies to preserve cognitive health.

Introduction Several nutrients may predict dementia risk. We characterized nutrient biomarker patterns, which integrate the complexity of nutrient exposure and biodisponibility associated with long-term risk of dementia in a large cohort of older persons, the Three-City study. Methods We included 666 nondemented participants with plasma measurements of 22 fat-soluble nutrients at baseline, who were followed up for 12 years for dementia. Results A "deleterious" pattern combining lower blood status in vitamin D, carotenoids, and polyunsaturated fats and higher saturated fats was strongly associated with a higher risk of dementia. Compared with individuals in the first quintile of the pattern score, participants in the highest quintile of score had an approximately fourfold increased risk of dementia (hazard ratio = 4.53 [95% confidence interval 1.99, 10.32], P for trend Discussion A blood pattern reflecting lower status in several nutrients among nondemented individuals appeared strongly associated with the long-term risk of dementia in this cohort.

ObjectiveTo investigate the optimal combination of dietary polyphenols associated with the long-term risk of dementia in a large prospective French cohort of older persons, the Three-City (3C) Study.MethodsWe included 1,329 older adults without dementia from the 3C study with assessment of intake of 26 polyphenol subclasses who were followed up for 12 years for dementia. Using partial least squares for Cox models, we identified a pattern of polyphenol intake associated with dementia risk.ResultsThe pattern combined several flavonoids (dihydroflavonols, anthocyanins, isoflavonoids, flavanones), stilbenes (including resveratrol), lignans, and other subclasses (hydroxybenzaldehydes, naphthoquinones, furanocoumarins). Compared with participants in the lower quintile of pattern score, those in the higher quintile had a 50% lower risk of dementia (95% confidence interval 20%–68%, p for trend ConclusionsIn this French cohort, a polyphenol pattern provided by a diet containing specific plant products (nuts, citrus, berries, leafy vegetables, soy, cereals, olive oil) accompanied by red wine and tea was associated with lower dementia risk.

B vitamins may lower the risk of dementia, yet epidemiological findings, mostly from countries with folic acid fortification, have remained inconsistent. We evaluated in a large French cohort of older persons the associations between dietary B vitamins and long-term incident dementia. We included 1321 participants from the Three-City Study who completed a 24 h dietary recall, were free of dementia at the time of diet assessment, and were followed for an average of 7.4 years. In Cox proportional hazards models adjusted for multiple potential confounders, including overall diet quality, higher intake of folate was inversely associated with the risk of dementia (p for trend = 0.02), with an approximately 50% lower risk for individuals in the highest compared to the lowest quintile of folate (HR = 0.47; 95% CI 0.28; 0.81). No association was found for vitamins B6 and B12. In conclusion, in a large French cohort with a relatively low baseline folate status (average intake = 278 µg/day), higher folate intakes were associated with a decreased risk of dementia.