September 3, 2025
A growing body of evidence shows that a traditional Mediterranean-style diet, rich in vegetables, fruits, beans, nuts, fish and olive oil, is good for the brain and cardiovascular health. Now a new study suggests that the heart-healthy diet may be especially beneficial for those who are at increased genetic risk for Alzheimer’s disease.
The study, from researchers at Harvard and other institutions, found that people who adhered most closely to a Mediterranean diet had a lower risk of developing Alzheimer’s disease and other forms of dementia as they aged. They also showed slower rates of cognitive decline. The protective effect of the diet was strongest in people who inherited two copies of the APOE-E4 gene, which greatly increases the risk of developing Alzheimer’s disease. The findings suggest that the Mediterranean diet may help offset genetic risks for Alzheimer’s.
“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 author Yuxi Liu, a research fellow at Brigham and Women’s Hospital. “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.”
For the study, the researchers followed over 5,700 men and women who were part of two long-running studies of health and aging: the Nurses’ Health Study and the Health Professionals Follow-Up Study. Participants filled out detailed questionnaires about the foods and drinks they consumed. Investigators also examined blood samples for a broad range of metabolites and assessed their genetic risks for dementia, including Alzheimer’s disease, by looking at their APOE gene status and other gene variants.
The APOE gene codes for a protein called apolipoprotein E that affects how cholesterol and other fats are processed in the body. Each of us carries two copies of the APOE gene, one inherited from our mother and the other from our father. A form of APOE, called APOE-E4, is the strongest known genetic risk factor for late-onset Alzheimer’s, the most common form of the disease. Those who carry one copy of APOE-E4 are at an up to three-fold increased risk of developing Alzheimer’s disease, while those who carry two copies of APOE-E4 are at an up to 12-fold increased risk.
The researchers followed participants for up to 34 years. They found that closely following the Mediterranean diet reduced the risk of developing Alzheimer’s disease or other forms of dementia. The benefit was highest for people with the APOE-E4 gene, especially those with two copies of the gene variant. In people who carried two copies of APOE-E4, a Mediterranean diet lowered dementia risk by at least 35 percent. People with the APOE-E4 gene also appeared to have distinct metabolites in their blood that responded to nutrients in the Mediterranean diet.
“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,” Dr. 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 APOE-E4 genetic variant.”
The findings, published in Nature Medicine, may be especially important for anyone who has Alzheimer’s in their family and who may have inherited the APOE-E4 gene. But just because you carry the APOE-E4 allele doesn’t mean you will develop Alzheimer’s disease. Many people who carry APOE-E4 never get Alzheimer’s. And many people who carry other variants of APOE do get Alzheimer’s.
Further research into the effects of diet on Alzheimer’s risk is needed. In the meantime, anyone might benefit from a Mediterranean-style diet. Even simple dietary modifications, such as adding more greens, berries, whole grains, olive oil and fish, may help to delay the onset of Alzheimer’s disease or reduce the risk of dementia as one ages. Foods to be avoided or eaten less often would include red meat, saturated fats like butter and stick margarine, sugary sweets and pastries, whole fat cheese, and fried, fast and ultraprocessed foods.
By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by Eric Schmidt, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.
Source: Yuxi Liu, Xiao Gu, Yanping Li, et al: “Interplay of genetic predisposition, plasma metabolome and Mediterranean diet in dementia risk and cognitive function.” Nature Medicine, August 25, 2025
