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The role of nutrition has been investigated for decades under the assumption of onesize-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.

ImportanceDementia threatens the well-being of older adults, making efforts toward prevention of great importance.ObjectiveTo evaluate the association of the Mediterranean–Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay (MIND) diet with the risk of dementia in 3 prospective studies and a meta-analysis.Design, Setting, and ParticipantsCohort analyses included the Whitehall II study (WII), the Health and Retirement Study (HRS), and the Framingham Heart Study Offspring cohort (FOS), and the meta-analysis included 11 cohort studies. Participants were middle-aged and older women and men from WII in 2002 to 2004, HRS in 2013, and FOS in 1998 to 2001 without dementia at the study baseline. Data were analyzed from May 25 to September 1, 2022.ExposuresMIND diet score was measured using food frequency questionnaires, and scores ranged from 0 to 15, with a higher score indicating higher adherence to the MIND diet.Main Outcome and MeasuresIncident all-cause dementia, with cohort-specific definitions.ResultsIncluded in this study were 8358 participants (mean [SD] age, 62.2 [6.0] years; 5777 male [69.1%]) from WII, 6758 participants (mean [SD] age, 66.5 [10.4] years; 3965 female [58.7%]) from HRS, and 3020 participants (mean [SD] age, 64.2 [9.1] years; 1648 female [54.6%]) from FOS. The mean (SD) baseline MIND diet score was 8.3 (1.4) in WII, 7.1 (1.9) in HRS, and 8.1 (1.6) in FOS. Over 166 516 person-years, a total of 775 participants (220 in WII, 338 in HRS, and 217 in FOS) developed incident dementia. In the multivariable-adjusted Cox proportional hazard model, higher MIND diet score was associated with lower risk of dementia (pooled hazard ratio [HR] for every 3-point increment, 0.83; 95% CI, 0.72-0.95; P for trend = .01; I2 = 0%). The associations were consistently observed in subgroups defined by sex, age, smoking status, and body mass index. In the meta-analysis of 11 cohort studies with 224 049 participants (5279 incident dementia cases), the highest tertile of MIND diet score was associated with lower risk of dementia compared with the lowest tertile (pooled HR, 0.83; 95% CI, 0.76-0.90; I2 = 35%).Conclusions and RelevanceResults suggest that adherence to the MIND diet was associated with lower risk of incident dementia in middle-aged and older adults. Further studies are warranted to develop and refine the specific MIND diet for different populations.

Background. Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) may have different effects on cognitive health due to their anti- or pro-inflammatory properties. Methods. We aimed to prospectively examine the relationships between n-3 and n-6 PUFA contents in serum phospholipids with incident all-cause dementia and Alzheimer’s disease dementia (AD). We included 1264 non-demented participants aged 84 ± 3 years from the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) multicenter-cohort study. We investigated whether fatty acid concentrations in serum phospholipids, especially eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), linoleic acid (LA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA), were associated with risk of incident all-cause dementia and AD. Results. During the follow-up window of seven years, 233 participants developed dementia. Higher concentrations of EPA were associated with a lower incidence of AD (hazard ratio (HR) 0.76 (95% CI 0.63; 0.93)). We also observed that higher concentrations of EPA were associated with a decreased risk for all-cause dementia (HR 0.76 (95% CI 0.61; 0.94)) and AD (HR 0.66 (95% CI 0.51; 0.85)) among apolipoprotein E ε4 (APOE ε4) non-carriers but not among APOE ε4 carriers. No other fatty acids were significantly associated with AD or dementia. Conclusions. Higher concentrations of EPA were associated with a lower risk of incident AD. This further supports a beneficial role of n-3 PUFAs for cognitive health in old age.

Background and Objectives:Diet may be a key contributor to brain health in midlife. In particular, Omega-3 fatty acids have been related to better neurological outcomes in older adults. However, studies focusing on midlife are lacking. We investigated the cross-sectional association of red blood cell (RBC) Omega-3 fatty acid concentrations with MRI and cognitive markers of brain aging in a community-based sample of predominantly middle-aged adults, and further explore effect modification by APOE genotype.Methods:We included participants from the Third-Generation and Omni 2 cohorts of the Framingham Heart Study attending their second examination. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations were measured from RBC using gas chromatography, and the Omega-3 index was calculated as EPA + DHA. We used linear regression models to relate Omega-3 fatty acid concentrations to brain MRI measures (i.e., total brain, total gray matter, hippocampal, and white matter hyperintensity volumes) and cognitive function (i.e., episodic memory, processing speed, executive function, and abstract reasoning) adjusting for potential confounders. We further tested for interactions between omega-3 fatty acid levels and APOE genotype (e4 carrier vs. non-carrier) on MRI and cognitive outcomes.Results:We included 2,183 dementia- and stroke-free participants (mean age 46 years, 53% women, 22% APOE-e4 carriers). In multivariable models, higher Omega-3 index was associated with larger hippocampal volumes (standard deviation unit beta ±standard error; 0.003 ±0.001, p=0.04), and better abstract reasoning (0.17 ±0.07, p=0.013). Similar results were obtained for DHA or EPA concentrations individually. Stratification by APOE-e4 status showed associations between higher DHA concentrations or Omega-3 index and larger hippocampal volumes in APOE-e4 non-carriers, whereas higher EPA concentrations were related to better abstract reasoning in APOE-e4 carriers. Finally, higher levels of all Omega-3 predictors were related to lower white matter hyperintensity burden but only in APOE-e4 carriers.Discussion:Our results, albeit exploratory, suggest that higher Omega-3 fatty acid concentrations are related to better brain structure and cognitive function in a predominantly middle-aged cohort free of clinical dementia. These associations differed by APOE genotype, suggesting potentially different metabolic patterns by APOE status. Additional studies in middle-age populations are warranted to confirm these findings.

Background: The mechanisms in the brain that explain the benefits of adherence to the Mediterranean diet (MeDiAd) for cognition are incompletely understood. Here, we investigated whether fractional anisotropy (FA) in hippocampus-relevant white-matter tracts mediates the association between baseline MeDiAd and verbal episodic memory over four years. Methods: Participants with baseline diffusion-weighted imaging data from the DELCODE cohort study were selected, including healthy older adults with and without subjective cognitive decline and patients with mild cognitive impairment (n = 376; age: 71.47 plus-or-minus sign 6.09 years; 48.7% female). Demographic, MeDiAd, and diffusion data were obtained at baseline. Verbal episodic memory was assessed at baseline and four yearly follow-ups. The association between baseline MeDiAd and verbal episodic memory's mean and rate of change over four years and the mediation of that association by baseline white-matter tracts were tested with latent growth curve modeling. Potential mediators were selected based on the association with hippocampal volume. Results: Baseline MeDiAd was associated with verbal episodic memory four years later (latent intercept; 95% confidence interval, CI [0.01, 0.32]) but not with its rate of change (latent slope) over this period. Only baseline Fornix FA, among four potential mediators (the cingulum ventral, corticospinal tract, and superior longitudinal fasciculus II), mediated this association (latent intercept; 95% CI [0.002, 0.09]). Conclusions: Higher Fornix FA explains the association between higher baseline MeDiAd and better memory four years later in pre-dementia stages. Fornix FA may be a useful response biomarker of Mediterranean diet interventions on memory.

Background: Previous studies suggest poor pulmonary function is associated with increased burden of cerebral white matter hyperintensities and brain atrophy among elderly individuals, but the results are inconsistent. Objective: To study the cross-sectional associations of pulmonary function with structural brain variables. Methods: Data from six large community-based samples (N = 11,091) were analyzed. Spirometric measurements were standardized with respect to age, sex, height, and ethnicity using reference equations of the Global Lung Function Initiative. Associations of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and their ratio FEV1/FVC with brain volume, gray matter volume, hippocampal volume, and volume of white matter hyperintensities were investigated using multivariable linear regressions for each study separately and then combined using random-effect meta-analyses. Results: FEV1 and FVC were positively associated with brain volume, gray matter volume, and hippocampal volume, and negatively associated with white matter hyperintensities volume after multiple testing correction, with little heterogeneity present between the studies. For instance, an increase of FVC by one unit was associated with 3.5 ml higher brain volume (95% CI: [2.2, 4.9]). In contrast, results for FEV1/FVC were more heterogeneous across studies, with significant positive associations with brain volume, gray matter volume, and hippocampal volume, but not white matter hyperintensities volume. Associations of brain variables with both FEV1 and FVC were consistently stronger than with FEV1/FVC, specifically with brain volume and white matter hyperintensities volume. Conclusion: In cross-sectional analyses, worse pulmonary function is associated with smaller brain volumes and higher white matter hyperintensities burden.

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