Abstract

AbstractBackgroundIn 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.MethodThe 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.ResultOverall, 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.ConclusionOur 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.

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