Mediterranean Diet, Alzheimer Disease Biomarkers and Brain Atrophy in Old Age

Abstract

Objective: To determine whether following a Mediterranean-like diet (MeDi) relates to cognitive functions and in vivo biomarkers for Alzheimer disease (AD), we analyzed cross-sectional data from the German DZNE-Longitudinal Cognitive Impairment and Dementia Study. METHOD: The sample (n=512, mean age: 69.5±5.9 years) included 169 cognitively normal participants and subjects at higher AD risk (53 with relatives with AD, 209 with subjective cognitive decline, and 81 with mild cognitive impairment). 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.

Figure 1. Positive Association Between MeDi and Brain Volume

(A) Positive association between Mediterranean diet (MeDi) score and brain gray matter volume at the whole-brain level. (B) Positive association between MeDi score and gray matter volume in a priori–defined regions of interest (ROIs) covering the bilateral hippocampi and parahippocampal gyri. All results are corrected for age, sex, total intracranial volume, and MRI scanner heterogeneity. Results are shown at p < 0.05 family-wise error corrected. Images are displayed in neurologic convention: left of the brain on the left of the image. Unthresholded T map is available at Neurovault (neurovault.org/collections/KMIELIOW/).

Figure 2. Graphical Display of Mediation and Moderated Mediation Models

Names of the paths and associated regression estimates are reported. Solid lines represent significant paths according to confidence intervals generated with bias corrected bootstrap with 10,000 replicates. Dashed lines mark nonsignificant regression paths. For models 2.1 and 2.2, in addition to the statistical models, the conceptual models are shown in the upper right corners, and simple slopes representing the interactions effects are shown below. A complete overview of direct and indirect effects is reported in table 4. Aβ_42/40 = ratio between β-amyloid₄₂ and β-amyloid₄₀; MeDi = Mediterranean diet; MEM = memory summary factor score; pTau = phosphorylated tau; rGMV = regional gray matter volume in bilateral hippocampi and parahippocampi.