Association of dietary and nutritional factors with cognitive decline, dementia, and depressive symptomatology in older individuals according to a neurogenesis-centred biological susceptibility to brain ageing.

Hippocampal neurogenesis (HN) occurs throughout the life course and is important for memory and mood. Declining with age, HN plays a pivotal role in cognitive decline (CD), dementia, and late-life depression, such that altered HN could represent a neurobiological susceptibility to these conditions. Pertinently, dietary patterns (e.g., Mediterranean diet) and/or individual nutrients (e.g., vitamin D, omega 3) can modify HN, but also modify risk for CD, dementia, and depression. Therefore, the interaction between diet/nutrition and HN may alter risk trajectories for these ageing-related brain conditions. Using a subsample (n = 371) of the Three-City cohort-where older adults provided information on diet and blood biobanking at baseline and were assessed for CD, dementia, and depressive symptomatology across 12 years-we tested for interactions between food consumption, nutrient intake, and nutritional biomarker concentrations and neurogenesis-centred susceptibility status (defined by baseline readouts of hippocampal progenitor cell integrity, cell death, and differentiation) on CD, Alzheimer's disease (AD), vascular and other dementias (VoD), and depressive symptomatology, using multivariable-adjusted logistic regression models. Increased plasma lycopene concentrations (OR [95% CI] = 1.07 [1.01, 1.14]), higher red meat (OR [95% CI] = 1.10 [1.03, 1.19]), and lower poultry consumption (OR [95% CI] = 0.93 [0.87, 0.99]) were associated with an increased risk for AD in individuals with a neurogenesis-centred susceptibility. Increased vitamin D consumption (OR [95% CI] = 1.05 [1.01, 1.11]) and plasma γ-tocopherol concentrations (OR [95% CI] = 1.08 [1.01, 1.18]) were associated with increased risk for VoD and depressive symptomatology, respectively, but only in susceptible individuals. This research highlights an important role for diet/nutrition in modifying dementia and depression risk in individuals with a neurogenesis-centred susceptibility.

Association of LIfestyle for BRAin health risk score (LIBRA) and genetic susceptibility with incident dementia and cognitive decline.

INTRODUCTION: Evaluating whether genetic susceptibility modifies the impact of lifestyle-related factors on dementia is critical for prevention. METHODS: We studied 5170 participants from a French cohort of older persons free of dementia at baseline and followed for up to 17 years. The LIfestyle for BRAin health risk score (LIBRA) including 12 modifiable factors was constructed at baseline (higher score indicating greater risk) and was related to both subsequent cognitive decline and dementia incidence, according to genetic susceptibility to dementia (reflected by the apolipoprotein E [APOE] ε4 allele and a genetic risk score [GRS]). RESULTS: The LIBRA was associated with higher dementia incidence, with no significant effect modification by genetics (hazard ratio for one point score = 1.09 [95% confidence interval, 1.05; 1.13]) in APOE ε4 non-carriers and = 1.15 [1.08; 1.22] in carriers; P = 0.15 for interaction). Similar findings were obtained with the GRS and with cognitive decline. DISCUSSION: Lifestyle-based prevention may be effective whatever the genetic susceptibility to dementia.

Chronic insomnia, high trait anxiety and their comorbidity as risk factors for incident type 2 diabetes mellitus.

The main objective of this study was to evaluate the association of the insomnia-anxiety comorbidity with incident type 2 diabetes (T2D) in a large prospective cohort. We selected adults without diabetes at baseline from the French NutriNet-Santé cohort who had completed the trait anxiety subscale of the Spielberger State-Trait Anxiety Inventory (STAI-T, 2013-2016) and a sleep questionnaire (2014); insomnia was defined according to established criteria. Using multivariable Cox models, we compared T2D risk across 4 groups: no insomnia or anxiety (reference), insomnia alone, anxiety alone (STAI-T ≥ 40), and comorbid anxiety and insomnia. Among 35,014 participants (mean baseline age: 52.4 ± 14.0 years; 76% women), 378 (1.1%) developed T2D over a mean follow-up of 5.9 ± 2.1 years. Overall, 28.5% of the sample had anxiety alone, 7.5%-insomnia alone, and 12.5%-both disorders. In the fully-adjusted model, a higher T2D risk was associated with anxiety-insomnia comorbidity (HR = 1.40; 95% CI 1.01, 1.94), but not with each disorder separately, compared to the group without insomnia or anxiety. The findings supported a positive association between anxiety-insomnia comorbidity and incident T2D among general-population adults. Future research using clinical diagnoses of mental disorders could confirm the findings and guide diabetes prevention programs.

Habitual coffee consumption and risk of dementia in older persons: modulation by CYP1A2 polymorphism.

Higher coffee consumption has been associated with reduced dementia risk, yet with inconsistencies across studies. CYP1A2 polymorphisms, which affects caffeine metabolism, may modulate the association between coffee and the risk of dementia and Alzheimer's disease (AD). We included 5964 participants of the Three-City Study (mean age 74 years-old), free of dementia at baseline when they reported their daily coffee consumption, with available genome-wide genotyping and followed for dementia over a median of 9.0 (range 0.8-18.7) years. In Cox proportional-hazards models, the relationship between coffee consumption and dementia risk was modified by CYP1A2 polymorphism at rs762551 (p for interaction = 0.034). In multivariable-adjusted models, coffee intake was linearly associated with a decreased risk of dementia among carriers of the C allele only ("slower caffeine metabolizers"; HR for 1-cup increased [95% CI] 0.90 [0.83-0.97]), while in non-carriers ("faster caffeine metabolizers"), there was no significant association but a J-shaped trend toward a decrease in dementia risk up to 3 cups/day and increased risk beyond. Thus, compared to null intake, drinking ≥ 4 cups of coffee daily was associated with a reduced dementia risk in slower but not faster metabolizers (HR [95% CI] for ≥ 4 vs. 0 cup/day = 0.45 [0.25-0.80] and 1.32 [0.89-1.96], respectively). Results were similar when studying AD and another CYP1A2 candidate polymorphism (rs2472304), but no interaction was found with CYP1A2 rs2472297 or rs2470893. In this cohort, a linear association of coffee intake to lower dementia risk was apparent only among carriers of CYP1A2 polymorphisms predisposing to slower caffeine metabolism.

Dairy products and brain structure in French older adults.

Among 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) (ß = -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.

Addressing unmeasured confounders in cohort studies: Instrumental variable method for a time-fixed exposure on an outcome trajectory.

Instrumental variable methods, which handle unmeasured confounding by targeting the part of the exposure explained by an exogenous variable not subject to confounding, have gained much interest in observational studies. We consider the very frequent setting of estimating the unconfounded effect of an exposure measured at baseline on the subsequent trajectory of an outcome repeatedly measured over time. We didactically explain how to apply the instrumental variable method in such setting by adapting the two-stage classical methodology with (1) the prediction of the exposure according to the instrumental variable, (2) its inclusion into a mixed model to quantify the exposure association with the subsequent outcome trajectory, and (3) the computation of the estimated total variance. A simulation study illustrates the consequences of unmeasured confounding in classical analyses and the usefulness of the instrumental variable approach. The methodology is then applied to 6224 participants of the 3C cohort to estimate the association of type-2 diabetes with subsequent cognitive trajectory, using 42 genetic polymorphisms as instrumental variables. This contribution shows how to handle endogeneity when interested in repeated outcomes, along with a R implementation. However, it should still be used with caution as it relies on instrumental variable assumptions hardly testable in practice.

Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies.

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

Broad Trends in Public Health and Epidemiology Informatics.

OBJECTIVES: The objective of this study is to highlight innovative research and contemporary trends in the area of Public Health and Epidemiology Informatics (PHEI). METHODS: Following a similar approach to last year's edition, a meticulous search was conducted on PubMed (with keywords including topics related to Public Health, Epidemiological Surveillance and Medical Informatics), examining a total of 2,022 scientific publications on Public Health and Epidemiology Informatics (PHEI). The resulting references were thoroughly examined by the three section editors. Subsequently, 10 papers were chosen as potential candidates for the best paper award. These selected papers were then subjected to peer-review by six external reviewers, in addition to the section editors and two chief editors of the IMIA yearbook of medical informatics. Each paper underwent a total of five reviews. RESULTS: Out of the 539 references retrieved from PubMed, only two were deemed worthy of the best paper award, although four papers had the potential to qualify in total. The first best paper by pertains to a study about the need for a new annotation framework due to inadequacies in existing methods and resources. The second paper elucidates the use of Weibo data to monitor the health of Chinese urbanites. The correlation between air pollution and health sensing was measured via generalized additive models. CONCLUSIONS: One of the primary findings of this edition is the dearth of studies identified for the PHEI section, which represents a significant decline compared to the previous edition. This is particularly surprising given that the post-COVID period should have led to an increased use of information and communication technology for public health issues.

Dietary pesticide exposure and non-communicable diseases and mortality: a systematic review of prospective studies among adults.

BACKGROUND: Research on the effect of pesticide exposure on health has been largely focused on occupational settings. Few reviews have synthesized the associations between dietary pesticide exposure and health outcomes in non-occupationally exposed adults. OBJECTIVE: We aim to summarize the evidence regarding dietary pesticide exposure and non-communicable diseases (NCD) in adults, using a systematic review of prospective studies. METHODS: Electronic and manual searches were performed until July 2023. The inclusion criteria were the following: 1) adults aged ≥ 18years, 2) (non)-randomized trials, prospective cohort studies, 3) dietary exposure to pesticides. A bias analysis was carried out using the Nutrition Evidence Systematic Review guidelines based on the Cochrane ROBINS-I. RESULTS: A total of 52 studies were retrieved and 6 studies that met the above criteria were included. Studies were conducted either in France or in the United States. The studies investigated the risk of cancer (n = 3), diabetes (n = 1), cardiovascular diseases (n = 1), and mortality (n = 1). The quality of the studies varied with overall grades derived from the bias analysis ranging from low to moderate bias. The level of evidence was estimated as low for the risk of cancer while the grading was not assignable for other outcomes, as only one study per outcome was available. CONCLUSIONS: Although further research is warranted to examine more in depth the relationships between low-dose chronic exposure to pesticides through diet and NCD outcomes in non-occupationally-exposed adults, studies suggest a possible role of exposure to dietary pesticide on health. Standardized methodological guidelines should also be proposed to allow for comparison across studies.

A Mediterranean Diet-Based Metabolomic Score and Cognitive Decline in Older Adults: A Case-Control Analysis Nested within the Three-City Cohort Study.

SCOPE: Evidence on the Mediterranean diet (MD) and age-related cognitive decline (CD) is still inconclusive partly due to self-reported dietary assessment. The aim of the current study is to develop an MD- metabolomic score (MDMS) and investigate its association with CD in community-dwelling older adults. METHODS AND RESULTS: This study includes participants from the Three-City Study from the Bordeaux (n = 418) and Dijon (n = 422) cohorts who are free of dementia at baseline. Repeated measures of cognition over 12 years are collected. An MDMS is designed based on serum biomarkers related to MD key food groups and using a targeted metabolomics platform. Associations with CD are investigated through conditional logistic regression (matched on age, sex, and education level) in both sample sets. The MDMS is found to be inversely associated with CD (odds ratio [OR] [95% confidence interval (CI)] = 0.90 [0.80-1.00]; p = 0.048) in the Bordeaux (discovery) cohort. Results are comparable in the Dijon (validation) cohort, with a trend toward significance (OR [95% CI] = 0.91 [0.83-1.01]; p = 0.084). CONCLUSIONS: A greater adherence to the MD, here assessed by a serum MDMS, is associated with lower odds of CD in older adults.

The role of cardiovascular health and vascular events in the relationship between excessive daytime sleepiness and dementia risk.

Many studies suggest a relationship between excessive daytime sleepiness (EDS) and dementia incidence, but the underlying mechanisms remain uncertain. The study aimed to investigate the role of cardiovascular burden in the relationship between EDS and dementia incidence over a 12-year follow-up in community-dwelling older adults. We performed analyses on 6171 subjects (aged ≥65 years) free of dementia and vascular disease at baseline. Participants self-reported EDS at baseline and an expert committee validated both prevalent and incident dementia. We defined cardiovascular burden by a low Cardiovascular Health score, constructed using the American Heart Association metrics, and incident vascular events. To explore the potential role of the cardiovascular burden in the relationship between EDS and dementia, we conducted mediation analyses with inverse odds ratio-weighted estimation, using multivariable-adjusted proportional hazard Cox and logistic regression models. Subjects with EDS had a higher risk of all-cause dementia (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.13-1.69) and dementia with vascular component (DVC) (HR 2.14, 95% CI 1.30-3.51), but not Alzheimer's disease (HR 1.18, 95% CI 0.93-1.51). Cardiovascular burden explained 5% (95% CI 4.1-5.2) and 11% (95% CI 9.7-11.3) of the relationship between EDS and all-cause dementia and DVC, respectively. These findings confirm that EDS may be implicated in the development of dementia and indicate a weaker than expected role of cardiovascular burden in the relationship between EDS and DVC.

Plasma carotenoids and risk of depressive symptomatology in a population-based cohort of older adults.

BACKGROUND: As part of a healthy diet, higher carotenoid intakes have been associated with a reduced risk of depression, mainly in adults, while prospective studies on plasma carotenoids in older adults are lacking. The aim of this study was to assess the prospective association between plasma carotenoids and the risk of Depressive Symptomatology (DS) in older adults. METHODS: The study sample was based on the Three-City cohort of adults aged 65y+ free from DS at enrollment in 1999. Plasma carotenoids were measured at baseline. DS was assessed every 2-3 years over 17 years and defined by a Center for Epidemiologic Studies-Depression Scale score ≥ 16 and/or by antidepressant use. The association between plasma carotenoids or carotenoid/lipids (cholesterol and triglycerides) ratio and the risk for DS was assessed through multiple random-effect logistic regression. RESULTS: The study sample was composed of 1010 participants (mean age 74 y (±4.9), 58 % of women) followed-up during a median time of 13.4 years. Plasma zeaxanthin and ratios of zeaxanthin/lipids, lutein+zeaxanthin/lipids and ß-carotene/lipids were independently associated with a significant reduced risk of DS over time (Odds ratio (OR) = 0.81, 95 % Confidence Interval (CI) [0.67;0.99], OR = 0.79 [0.67;0.98], OR = 0.79 [0.64;0.94] and OR = 0.80 [0.66;0.97] for +1 standard deviation of each exposure respectively). LIMITATIONS: Plasma carotenoids were only available at study baseline. CONCLUSION: Focusing on circulating carotenoids and considering lipids levels, the present results suggested an association between higher levels of plasma zeaxanthin, combined lutein+zeaxanthin and ß-carotene and a decreased risk of DS over time in older adults.

Nutritional metabolism and cerebral bioenergetics in Alzheimer's disease and related dementias.

Disturbances in the brain's capacity to meet its energy demand increase the risk of synaptic loss, neurodegeneration, and cognitive decline. Nutritional and metabolic interventions that target metabolic pathways combined with diagnostics to identify deficits in cerebral bioenergetics may therefore offer novel therapeutic potential for Alzheimer's disease (AD) prevention and management. Many diet-derived natural bioactive components can govern cellular energy metabolism but their effects on brain aging are not clear. This review examines how nutritional metabolism can regulate brain bioenergetics and mitigate AD risk. We focus on leading mechanisms of cerebral bioenergetic breakdown in the aging brain at the cellular level, as well as the putative causes and consequences of disturbed bioenergetics, particularly at the blood-brain barrier with implications for nutrient brain delivery and nutritional interventions. Novel therapeutic nutrition approaches including diet patterns are provided, integrating studies of the gut microbiome, neuroimaging, and other biomarkers to guide future personalized nutritional interventions.

Exploration of the Gut-Brain Axis through Metabolomics Identifies Serum Propionic Acid Associated with Higher Cognitive Decline in Older Persons.

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.

Mediterranean Diet Adherence and Risk of Depressive Symptomatology in a French Population-Based Cohort of Older Adults.

Several foods from the Mediterranean Diet (MeDi) have already been characterized as beneficial for depression risk, while studies focusing on adherence to the overall MeDi are lacking among older adults at higher risk of depression. The aim of this study was to assess the association between MeDi adherence and the risk of depressive symptomatology (DS) in an older French cohort followed for 15 years. Participants from the Three-City Bordeaux cohort answered a food frequency questionnaire used to assess their MeDi adherence. The Center for Epidemiologic Studies Depression (CES-D) scale score of 16 or greater and/or use of antidepressant treatment ascertained at each visit defined incident DS. Random-effect logistic regression models were adjusted for potential confounders. Among 1018 participants, aged 75.6 years (SD 4.8 years) on average at baseline, 400 incident cases of DS were identified during the follow-up. Only when restricting the definition of DS to a CES-D score ≥ 16 was a borderline-significant trend towards a benefit of greater adherence to the MeDi with reduced odds of DS found (p-value = 0.053). In this large sample of older French adults, a potential benefit of greater adherence to the MeDi regarding the risk of DS would depend on the definition of DS.

The Plasma Oxylipin Signature Provides a Deep Phenotyping of Metabolic Syndrome Complementary to the Clinical Criteria.

Metabolic syndrome (MetS) is a complex condition encompassing a constellation of cardiometabolic abnormalities. Oxylipins are a superfamily of lipid mediators regulating many cardiometabolic functions. Plasma oxylipin signature could provide a new clinical tool to enhance the phenotyping of MetS pathophysiology. A high-throughput validated mass spectrometry method, allowing for the quantitative profiling of over 130 oxylipins, was applied to identify and validate the oxylipin signature of MetS in two independent nested case/control studies involving 476 participants. We identified an oxylipin signature of MetS (coined OxyScore), including 23 oxylipins and having high performances in classification and replicability (cross-validated AUCROC of 89%, 95% CI: 85-93% and 78%, 95% CI: 72-85% in the Discovery and Replication studies, respectively). Correlation analysis and comparison with a classification model incorporating the MetS criteria showed that the oxylipin signature brings consistent and complementary information to the clinical criteria. Being linked with the regulation of various biological processes, the candidate oxylipins provide an integrative phenotyping of MetS regarding the activation and/or negative feedback regulation of crucial molecular pathways. This may help identify patients at higher risk of cardiometabolic diseases. The oxylipin signature of patients with metabolic syndrome enhances MetS phenotyping and may ultimately help to better stratify the risk of cardiometabolic diseases.

Patterns of polyphenol intake and risk of depressive symptomatology in a population-based cohort of older adults.

BACKGROUND & AIMS: Current evidence suggests that some isolated polyphenols (PP) may exert promising effects for the risk of depression in young adults, however studies among older adults remain limited. The aim of the current study was to examine the prospective association between patterns of PP intake and the risk of depressive symptomatology (DS) in older adults. METHODS: The study sample was based on the Three-City (3C) Bordeaux cohort of adults aged 65 years and over and without DS at the time of recruitment. The intakes of PP, summarised into 21 PP classes, were determined using a 24-h recall combined with the Phenol-Explorer database. In addition, the patterns of PP intake were identified by a Principal Component Analysis (PCA). DS was evaluated using the Center for Epidemiologic Studies Depression Scale (CES-D) over a period of 15 years with a reassessment every 2-3 years. The incident DS was reported for CES-D score ≥16 and/or the use of antidepressant treatment. The association between the patterns of PP intake at baseline and the risk of DS was computed using multivariate random-effect logistic regression models. RESULTS: Among the 1074 participants (mean age 75.7 y, SD 4.8 y), 423 (39.4%) developed a DS during the follow-up. Distinct patterns of PP intake were identified, explaining up to 50% of the variance. The two first patterns, mainly driven by stilbenes and dihydroflavonols and by hydroxyicnnamic acid and alkylmethoxyphenols respectively, were not associated with the odds of DS. Furthermore, a higher score on the third pattern, mainly driven by monomeric flavanols and theaflavins, was associated with a significant 27% lower risk of DS over time (Odd Ratio = 0.73, 95% Confidence Interval [0.55; 0.97]). CONCLUSION: This prospective study suggested that a pattern high in monomeric flavanols and theaflavins intakes, mainly provided by tea, was associated with a reduced risk of DS in older adults. These results provide promising evidence on combined PP intakes that would require further confirmation in other samples.

Impaired hippocampal neurogenesis in vitro is modulated by dietary-related endogenous factors and associated with depression in a longitudinal ageing cohort study.

Environmental factors like diet have been linked to depression and/or relapse risk in later life. This could be partially driven by the food metabolome, which communicates with the brain via the circulatory system and interacts with hippocampal neurogenesis (HN), a form of brain plasticity implicated in depression aetiology. Despite the associations between HN, diet and depression, human data further substantiating this hypothesis are largely missing. Here, we used an in vitro model of HN to test the effects of serum samples from a longitudinal ageing cohort of 373 participants, with or without depressive symptomology. 1% participant serum was applied to human fetal hippocampal progenitor cells, and changes in HN markers were related to the occurrence of depressive symptoms across a 12-year period. Key nutritional, metabolomic and lipidomic biomarkers (extracted from participant plasma and serum) were subsequently tested for their ability to modulate HN. In our assay, we found that reduced cell death and increased neuronal differentiation were associated with later life depressive symptomatology. Additionally, we found impairments in neuronal cell morphology in cells treated with serum from participants experiencing recurrent depressive symptoms across the 12-year period. Interestingly, we found that increased neuronal differentiation was modulated by increased serum levels of metabolite butyrylcarnitine and decreased glycerophospholipid, PC35:1(16:0/19:1), levels - both of which are closely linked to diet - all in the context of depressive symptomology. These findings potentially suggest that diet and altered HN could subsequently shape the trajectory of late-life depressive symptomology.

Nutrition state of science and dementia prevention: recommendations of the Nutrition for Dementia Prevention Working Group.

Observational studies suggest that nutritional factors have a potential cognitive benefit. However, systematic reviews of randomised trials of dietary and nutritional supplements have reported largely null effects on cognitive outcomes and have highlighted study inconsistencies and other limitations. In this Personal View, the Nutrition for Dementia Prevention Working Group presents what we consider to be limitations in the existing nutrition clinical trials for dementia prevention. On the basis of this evidence, we propose recommendations for incorporating dietary patterns and the use of genetic, and nutrition assessment tools, biomarkers, and novel clinical trial designs to guide future trial developments. Nutrition-based research has unique challenges that could require testing both more personalised interventions in targeted risk subgroups, identified by nutritional and other biomarkers, and large-scale and pragmatic study designs for more generalisable public health interventions across diverse populations.

Dietary Glycemic Load and Plasma Amyloid-ß Biomarkers of Alzheimer's Disease.

Previous studies have highlighted links between a high-glycemic-load (GL) diet and Alzheimer's disease in apolipoprotein E ε4 (APOE4) carriers. However, the impact of high-GL diet on plasma amyloid-ß (Aß), an Alzheimer's disease hallmark that can be detected decades before clinical symptomatology, is unknown. This study examined the association between plasma Aß peptides (Aß40, Aß42 concentration and Aß42/Aß40 ratio) and GL. The influence of the GL of four meal types (breakfast, lunch, afternoon snack, and dinner) was also determined. From the prospective Three-City study, 377 participants with plasma Aß measurements, and who completed the Food Frequency Questionnaire, were selected. The association between plasma Aß and GL was tested using an adjusted linear regression model. Lunch GL was associated with a lower plasma Aß42 concentration (ß = -2.2 [CI = -4.27, -0.12], p = 0.038) and lower Aß42/Aß40 ratio (ß = -0.009 [CI = -0.0172, -0.0007], p = 0.034) in the model adjusted for center, age, sex, education level, APOE4 status, energy intake, serum creatinine, total cholesterol, and Mediterranean-like diet. No significant association was found with the GL of the other meal types. These results suggest that dietary GL may independently modulate the plasma Aß of the APOE4 status. The mechanism underlying diet, metabolic response, and Aß peptide regulation must be elucidated.