Older adults at highest genetic risk for Alzheimer’s disease may benefit the most from following a Mediterranean-style diet, according to new research that tracked thousands of participants for more than three decades.
The study, published in Nature Medicine, followed 4,215 women from the Nurses’ Health Study for up to 34 years. It found that those with the greatest genetic vulnerability to Alzheimer’s showed the strongest protective benefits from Mediterranean diet adherence. Researchers focused on people carrying two copies of the APOE4 gene variant, which increases Alzheimer’s risk eight-12-fold compared to individuals with the common APOE3 genotype. Carrying one copy increases risk three-to-fourfold.
“These findings suggest that dietary strategies, specifically the Mediterranean diet, could help reduce the risk of cognitive decline and stave off dementia by broadly influencing key metabolic pathways,” study first author Yuxi Liu, PhD, of Brigham and Women’s Hospital, said.
The research revealed that people with the highest genetic risk had distinct blood metabolite profiles — small molecules that reflect how the body processes food and carries out normal functions. The scientists identified 57 metabolites whose associations with dementia risk varied significantly by APOE4 genetic status, with these differences detectable decades before disease onset.
For people with two copies of the high-risk APOE4 gene variant, the Mediterranean diet’s protective effects were partly tied to healthier changes in blood molecules. About 40% of the diet’s benefit in this group was explained by these changes, a link not seen in people without the risky genes.
The Mediterranean diet emphasizes vegetables, fruits, whole grains, legumes, nuts, fish and healthy fats like olive oil, while limiting red meat and processed foods. Previous research, including the landmark PREDIMED trial, has established this eating pattern as the only dietary approach causally linked to cognitive benefits in a randomized controlled trial.
The findings were replicated in 1,490 men from the Health Professionals Follow-Up Study, supporting the results’ generalizability across sexes.
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