Objective:To determine if following a Mediterranean-like diet (MeDi) relates to cognitive functions and in vivo biomarkers for Alzheimer’s disease (AD), we analyzed cross-sectional data from the German Longitudinal Cognitive Impairment and Dementia StudyMethod:The sample (n=512, mean age: 69.5±5.9 years) included 169 cognitively normal participants and subjects at higher AD risk (53 AD relatives, 209 SCD and 81 MCI). We defined MeDi adherence based on the Food Frequency Questionnaire. Brain volume outcomes were generated via voxel-based morphometry on T1-MRI and cognitive performance with an extensive neuropsychological battery. AD-related biomarkers (Aβ42/40 ratio, pTau181) in cerebrospinal fluid were assessed in n=226 individuals. We analyzed the associations between MeDi and the outcomes with linear regression models controlling for several covariates. Additionally, we applied hypothesis-driven mediation and moderation analysis.Results:Higher MeDi adherence related to larger mediotemporal gray matter volume (p<0.05 FWE corrected), better memory (β±SE = 0.03 ± 0.02; p=0.038), and less amyloid (Aβ42/40 ratio, β±SE = 0.003 ± 0.001; p=0.008) and pTau181 pathology (β±SE = -1.96±0.68; p=0.004). Mediotemporal volume mediated the association between MeDi and memory (40% indirect mediation). Finally, MeDi favorably moderated the associations between Aβ42/40 ratio, pTau181 and mediotemporal atrophy. Results were consistent correcting for ApoE-ε4 status.Conclusion:Our findings corroborate the view of MeDi as a protective factor against memory decline and mediotemporal atrophy. Importantly, they suggest that these associations might be explained by a decrease of amyloidosis and tau-pathology. Longitudinal and dietary intervention studies should further examine this conjecture and its treatment implications.

Purpose To investigate cross-sectional associations between dietary patterns and cognitive functioning in elderly free of dementia. Methods Data of 389 participants from the German DELCODE study (52% female, 69 ± 6 years, mean Mini Mental State Score 29 ± 1) were included. The sample was enriched with elderly at increased risk for Alzheimer's disease (AD) by including participants with subjective cognitive decline, mild cognitive impairment (MCI) and siblings of AD patients. Mediterranean and MIND diets were derived from 148 Food Frequency Questionnaire items, and data-driven patterns by principal component analysis (PCA) of 39 food groups. Associations between dietary patterns and five cognitive domain scores were analyzed with linear regression analyses adjusted for demographics (model 1), and additionally for energy intake, BMI, other lifestyle variables and APOe4-status (model 2). For PCA-derived dietary components, final model 3 included all other dietary components. Results In fully adjusted models, adherence to Mediterranean and MIND diet was associated with better memory. The 'alcoholic beverages' PCA component was positively associated with most cognitive domains. Exclusion of MCI subjects (n = 60) revealed that Mediterranean and MIND diet were also related to language functions; associations with the alcoholic beverages component were attenuated, but most remained significant. Conclusion In line with data from elderly population samples, Mediterranean and MIND diet and some data-derived dietary patterns were related to memory and language function. Longitudinal data are needed to draw conclusions on the putative effect of nutrition on the rate of cognitive decline, and on the potential of dietary interventions in groups at increased risk for AD.

Background In the absence of effective therapies against Alzheimer's disease (AD), the identification of modifiable risk/protective factors is crucial. Many studies have shown the influence of diet on aging and diseases of late life, including neurodegenerative disorders. However, the mechanisms underlying these effects are largely unknown. Here we investigated the effects of Mediterranean diet (MD) on memory performance and on biomarkers for AD in a large cohort of non‐demented individuals from the German multicenter Longitudinal Cognitive Impairment and Dementia Study (DELCODE). Specifically, we aimed to test if the know association between adherence to MD and improved memory is mediated by effects on hippocampal volume and biomarkers of AD pathology in cerebrospinal fluid. Method The sample included memory clinic patients with subjective cognitive decline (n=235) or mild cognitive impairment (n=100), cognitively normal siblings of AD patients (n=56), and healthy volunteers (n=179). A MD score was computed for each subject by means of an established Food Frequency Questionnaire. Linear regression models adjusted for age, gender and education were run to investigate the association between MD and 1) memory performance, 2) total‐tau, phosphorylated‐tau and amyloid‐beta 42 levels from cerebrospinal fluid and 3) bilateral hippocampal volumes obtained via segmentation of 3T MRI data in Freesurfer. Result Overall, higher MD scores were associated with better memory function, lower levels of total and phosphorylated tau proteins and increased volume in bilateral hippocampi. In contrast, no significant effects of MD on amyloid were identified. Subsequent mediation analyses revealed that the effect of MD on memory performance was mediated by both hippocampal volumes and tau protein levels. Conclusion Our results support the view of Mediterranean diet as a protective factor against memory decline and AD‐related neurodegeneration. Moreover, we propose that MD acts on hippocampal volume and tau protein accumulation, which in turn leads to preserved memory performance. Further studies are needed to validate and expand our findings, especially investigating the effects of specific combinations of nutrients and their interplay with AD‐biomarkers and cognitive decline during follow‐up.