A Harvard study finds that following a Mediterranean diet can lower dementia risk for those with high genetic susceptibility, including APOE4 carriers
New research suggests that following a Mediterranean-style diet may help counteract a person’s genetic risk for Alzheimer’s disease. The study, led by researchers from Mass General Brigham, Harvard T.H. Chan School of Public Health, and the Broad Institute, found that individuals at high genetic risk for dementia who adhered to a diet rich in vegetables, fruits, nuts, and whole grains and low in red and processed meats experienced slower cognitive decline and a reduced likelihood of developing Alzheimer’s.
The findings are detailed in Nature Medicine.
Proven cognitive gains from Mediterranean eating
Exploring the genetic and metabolic basis of Alzheimer’s disease and related dementias is a vital area of research, as it helps scientists understand why some individuals are more susceptible than others. Alzheimer’s disease is known to have a strong genetic component, with heritability estimated at up to 80%.
In particular, the gene named apolipoprotein E or APOE has emerged as the strongest genetic risk factor for sporadic Alzheimer’s disease, which is the most common form of Alzheimer’s and is not directly inherited from parents. People who carry one copy of the APOE4 variant have a three- to fourfold higher risk of developing Alzheimer’s, and people with two copies of the APOE4 variant have a 12-fold higher risk of Alzheimer’s than those without.
To establish a link between the Mediterranean diet, dementia risk, and the influence of blood metabolites linked to cognitive health, the researchers analysed data from 4,215 women in the Nurses’ Health Study, following participants from 1989 to 2023 (average age 57 at baseline). To validate their findings, the researchers analysed similar data from 1,490 men in the Health Professionals Follow-Up Study, followed from 1993 to 2023.
“One reason we wanted to study the Mediterranean diet is because it is the only dietary pattern that has been causally linked to cognitive benefits in a randomized trial,” said study first author Yuxi Liu, a research fellow in the Department of Medicine at Brigham and Women’s Hospital and a postdoctoral fellow at the Harvard Chan School and the Broad. “We wanted to see whether this benefit might be different in people with varying genetic backgrounds, and to examine the role of blood metabolites, the small molecules that reflect how the body processes food and carries out normal functions.”
Lower risk of Alzheimer’s disease after following a Mediterranean diet
The researchers analysed long-term dietary patterns using food frequency questionnaires and examined participants’ blood samples for a broad range of metabolites, which are small molecules that reflect how the body processes food and carries out normal functions. They assessed genetic data to understand each participant’s inherited risk for Alzheimer’s disease and were followed over time for new cases of dementia. A subset of 1,037 women underwent regular telephone-based cognitive testing.
The researchers discovered that the people following a more Mediterranean diet had a lower risk of developing dementia and showed slower cognitive decline. The protective effect of the diet was most potent in the high-risk group with two copies of the APOE4 gene variant, suggesting that diet may help offset genetic risk.
“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,” Liu said. “This recommendation applies broadly, but it may be even more important for individuals at a higher genetic risk, such as those carrying two copies of the APOE4 genetic variant.”
However, a study limitation noted was that the cohort consisted only of well-educated individuals of European ancestry, and further research is needed to diversify the findings.
“In future research, we hope to explore whether targeting specific metabolites through diet or other interventions could provide a more personalized approach to reducing dementia risk,” Liu said, opening up a new frontier in Alzheimer’s prevention.
