Mediterranean Diet Promising in Lowering Dementia Risk

A US cohort study revealed genotype-dependent metabolic signatures of cognitive health and support precision nutrition approaches, such as Mediterranean diet for Alzheimer’s disease and related dementias (AD/ADRD) prevention. The study analyzed genetic, plasma metabolomic, and dietary data from 4,215 women and 1,490 men in prospective cohorts. The associations between 57 metabolites and dementia risk varied by APOE4 status or other AD/ADRD variants. For instance, cholesteryl esters and sphingomyelins were most strongly linked to higher dementia risk in APOE4 homozygotes, while glycerides showed protective associations specific to this group. Additionally, dimethylguanidino-valeric acid was more strongly tied to dementia risk among carriers of the rs2154481-C allele (APP). Notably, adherence to the Mediterranean diet appeared more effective at modulating dementia-related metabolites in APOE4 homozygotes, suggesting potential for targeted prevention strategies. Incorporating metabolomic data modestly improved dementia risk prediction, especially in early follow-up, and Mendelian randomization identified 19 metabolites with potential causal links to cognitive outcomes, including protective effects of 4-guanidinobutanoate, carotenoids, and N6-carbamoylthreonyladenosine. AD/ADRD have a strong genetic component, with APOE4 homozygotes now recognized as a distinct subtype. Source: https://www.nature.com/