A new study led by researchers from Mass General Brigham, the Harvard T.H. Chan School of Public Health, and the Broad Institute of MIT and Harvard suggests that following a Mediterranean-style diet may lower the risk of dementia. Published in Nature Medicine, the research found that people at the highest genetic risk for Alzheimer’s disease saw the most significant benefit from this diet, showing a marked reduction in dementia risk compared with those at lower genetic risk.
The Mediterranean diet—rich in fruits, vegetables, whole grains, legumes, olive oil, and fish—has previously been the only dietary pattern shown in a randomised trial to improve cognition directly. “We wanted to know if the benefits might vary depending on genetic background and whether diet could affect blood metabolites linked to brain health,” said first author Yuxi Liu, PhD, a research fellow at Brigham and Women’s Hospital and the Harvard Chan School.
Genetics play a significant role in Alzheimer’s, with heritability estimated at up to 80 per cent. The APOE gene is the most substantial known risk factor: carrying one copy of the APOE4 variant triples or quadruples risk, while having two copies increases risk twelve-fold. The study aimed to determine whether dietary habits could influence outcomes in individuals with this heightened susceptibility.
To answer this, the researchers analysed data from more than 4,200 women in the Nurses’ Health Study and 1,490 men in the Health Professionals Follow-Up Study, with participants followed for up to three decades. Diet was assessed through food questionnaires, blood was analysed for hundreds of metabolites, and genetic data were used to estimate Alzheimer’s risk. Some participants also completed regular cognitive testing by telephone.
The results showed that those adhering more closely to a Mediterranean-style diet were less likely to develop dementia and experienced slower cognitive decline. The most substantial benefits were observed in individuals carrying two copies of the APOE4 variant, suggesting diet may counterbalance a significant inherited risk.
The authors cautioned that the findings were drawn from largely well-educated participants of European ancestry and that more diverse studies are needed. They also emphasised that while genetics and metabolomics offer valuable clues, these tools are not yet part of everyday clinical practice. Future research will aim to determine whether tailoring diet to genetic and metabolic profiles can provide even stronger, more personalised protection against Alzheimer’s disease.
More information: Yuxi Liu et al, Interplay of genetic predisposition, plasma metabolome and Mediterranean diet in dementia risk and cognitive function, Nature Medicine. DOI: 10.1038/s41591-025-03891-5
Journal information: Nature Medicine Provided by Mass General Brigham
