Mediterranean diet may help offset genetic risk for Alzheimer’s disease

New research suggests that following a Mediterranean-style diet may help reduce the risk of Alzheimer’s disease, even in people with a high genetic predisposition for the condition.

The study, published in Nature Medicine and led by investigators from Mass General Brigham, Harvard T.H. Chan School of Public Health, and the Broad Institute of MIT and Harvard, found that people with the highest genetic risk who followed a Mediterranean diet experienced slower cognitive decline and a lower risk of dementia compared with those at lower genetic risk who did not follow the diet.

What is the Mediterranean diet?

The Mediterranean diet emphasizes vegetables, fruits, nuts, whole grains, legumes, fish, and healthy fats, while limiting red meat and processed foods. It has previously been associated with improved heart and brain health.

“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 at Brigham and Women’s Hospital and a postdoctoral fellow at Harvard Chan School and the Broad Institute.

Researchers aimed to determine whether the benefits of this dietary pattern vary depending on a person’s genetic background and how metabolism may influence brain health.

“We wanted to see whether this benefit might be different in people with varying genetic backgrounds, and to examine the role of blood metabolites,” Liu added.

Understanding genetic risk for Alzheimer’s

Alzheimer’s disease has a strong genetic component, with heritability estimated at up to 80 percent. One of the most important genetic factors is the APOE gene.

People who carry one copy of the APOE4 variant have a three- to fourfold higher risk of developing Alzheimer’s disease. Those with two copies face up to a 12-fold increased risk compared with non-carriers.

How the study was conducted

Researchers analyzed data from 4,215 women in the Nurses’ Health Study, followed from 1989 to 2023, with an average baseline age of 57. To validate the findings, they also studied 1,490 men from the Health Professionals Follow-Up Study, tracked from 1993 to 2023.

Diet was assessed using long-term food frequency questionnaires, while blood samples were analyzed to measure metabolites — small molecules that reflect how the body processes food and maintains biological functions.

Participants’ genetic data were used to estimate Alzheimer’s risk, and they were followed over time for the development of dementia. A subset of 1,037 women also underwent regular cognitive testing via telephone assessments.

Key findings

Researchers found that participants who adhered more closely to a Mediterranean-style diet had:

  • A lower risk of developing dementia
  • Slower rates of cognitive decline

The protective effects were especially strong among individuals with the highest genetic risk, including those carrying two copies of the APOE4 variant.

“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.

He added that while the recommendation applies broadly, it may be particularly important for those at higher genetic risk.

Limitations and future research

The researchers noted that the study population consisted mainly of well-educated individuals of European ancestry, meaning the results may not fully apply to more diverse populations.

They also pointed out that genetic testing for APOE status and metabolomic profiling are not yet part of standard clinical practice for Alzheimer’s risk prediction.

“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.

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