Mediterranean Diet Can Mitigate Genetic Risk Factors for Alzheimer's Disease

Recent research conducted by teams from Mass General Brigham, Harvard T.H. Chan School of Public Health, and the Broad Institute of MIT and Harvard indicates that adopting a Mediterranean-style diet may significantly lower the risk of developing dementia. Published in Nature Medicine, the study highlights that individuals with a higher genetic predisposition to Alzheimer's disease, particularly carriers of the APOE4 gene variant, experience a more pronounced benefit from following this dietary pattern.

The study analyzed data from over 4,200 women in the Nurses' Health Study, spanning from 1989 to 2023, with participant ages averaging 57 at the start. Similar findings were validated through data from nearly 1,500 men in the Health Professionals Follow-Up Study. Researchers assessed long-term dietary habits using food frequency questionnaires, examined blood samples for a broad spectrum of metabolites, and included genetic data to evaluate inherited Alzheimer's risk. Participants were monitored for the development of dementia, and a subset underwent regular cognitive testing.

Findings revealed that adherence to a Mediterranean diet was associated with a reduced risk of dementia and slower cognitive decline. Notably, the protective effects were strongest among those carrying two copies of the APOE4 gene, indicating that diet can potentially offset genetic risk factors. Lead researcher Yuxi Liu emphasized that this dietary pattern is uniquely linked to cognitive benefits demonstrated in controlled trials, and that targeting specific metabolic pathways through diet may offer personalized strategies to prevent cognitive decline.

The study also underscores that Alzheimer's disease has a substantial genetic component, with heritability estimates reaching up to 80%. The APOE4 gene variant markedly increases risk—carriers with one copy face 3 to 4 times higher risk, while those with two copies have up to a 12-fold increase. Given these genetic considerations, dietary interventions like the Mediterranean diet could serve as a vital tool in reducing dementia incidence, especially among high-risk populations.

However, the researchers note limitations, including the study's focus on well-educated individuals of European ancestry, indicating a need for further research in more diverse populations. Since genetic testing for APOE status is not routine in clinical practice, translating these findings into everyday medical recommendations remains a work in progress. Future research aims to explore how targeting specific blood metabolites through diet or other interventions might advance personalized approaches to dementia prevention.

Overall, this study suggests that wider adoption of the Mediterranean diet could be a practical strategy to lower dementia risk, particularly for those with a strong genetic predisposition, highlighting the importance of diet in cognitive health.