Small changes in the sequence of one particular gene can dramatically increase a person’s risk of developing Alzheimer’s disease. But new research has suggested that adhering to the Mediterranean diet may offset a carrier’s risk of developing the disease. The findings have been reported in Nature Medicine.
"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 first study author Yuxi Liu, PhD, a postdoctoral fellow at the Harvard Chan School and Broad, among other appointments. "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."
Changes in one gene called apolipoprotein E (APOE) are known to have a strong link to the development of Alzheimer’s disease. People who carry one copy of a variant of that gene called APOE4 have a three to four times greater risk of developing Alzheimer’s compared to people who have APOE2, while people with two copies of APOE4 have as much as a twelve times greater risk of the disease that non-carriers.
In this study, The researchers wanted to know more about whether diet could help offset this genetic risk.
They assessed data obtained from 4,215 women who were followed from 1989 to 2023 and had an average age of 57 at the start of the study. The findings from this dataset were then confirmed using similar data from 1,490 men who were followed from 1993 to 2023.
The dietary patterns of these volunteers were tracked for many years, and a range of biomarkers in blood samples provided a clinical assessment. The investigators also had access to genetic data for the study participants, and cognitive tests for some of them.
This research showed that people who tended to eat a Mediterranean-style diet more often had a lower risk of dementia, and cognitive decline was slightly slower in these people.
The strongest protective effect was seen in individuals with the highest Alzheimer’s risk: those with two copies of APOE4. Diet, therefore, may be reducing that genetic risk significantly.
"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."
More research will be needed to understand the physiological basis of this protective mechanism, as well as to confirm these findings in more diverse groups of people, since this work focused on individuals with European ancestry.
Since many people also do not know their APOE status, more efforts will be needed before these findings could translate into clinical recommendations.
"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.
Sources: Mass General Brigham, Harvard Medical School, Nature Medicine