The new findings add to those from prior research showing that a diet rich in fruits, vegetables, whole grains, olive oil, beans, and fish can boost brain health.
“Our study shows that genetics are not destiny, and lifestyle choices like following a Mediterranean diet can still make a big difference,” says lead author Yuxi Liu, PhD, a research fellow in the department of medicine at Brigham and Women’s Hospital in Boston.
How Genes Can Raise Dementia Risk
Late-onset Alzheimer’s, which occurs in people 65 and older, is the most common form of Alzheimer’s, making up an estimated 90 to 95 percent of cases.
People with one copy of the APOE4 variant have 3 to 4 times higher odds of developing Alzheimer’s than people without this gene. People with two copies of APOE4 have a 12-fold higher risk.
About 15 to 25 percent of all people have one copy of APOE4, and 2 to 5 percent have two copies.
Mediterranean Diets Cut Dementia Risk by 35 Percent in the Highest Risk Group
To see how diet affected Alzheimer’s risk, researchers recruited about 4,200 women who were 57 on average when they joined, and about 1,500 men who were 63 on average. The scientists kept tabs on the participants for up to 34 years.
Participants completed questionnaires about their diets and gave blood samples at the beginning of the study, which helped researchers determine the effect of diet on dementia-related metabolites (small molecules related to metabolism).
A subset of about 1,000 women underwent regular telephone-based cognitive testing.
A total of 485 women and 121 men developed dementia over the course of the study.
Study results, published in the journal Nature Medicine, showed that people with two copies of the APOE4 gene who were following a Mediterranean diet had a 35 percent lower risk of developing dementia compared with those with the same genetic profile who did not follow the Mediterranean diet.
People following a Mediterranean diet who had one APOE4 copy saw their Alzheimer’s risk drop by 4 percent.
Dr. Liu and her team noted that higher adherence to the Mediterranean diet was associated with further reduction in dementia risk.
Blood Tests Shed Light on the Diet-Dementia Link
Because researchers collected blood samples from participants at the start of the study, the results suggest that markers measured early in life can provide important clues about dementia risk many years before symptoms occur, according to Liu.
In a test that measures whether certain metabolites in the blood may play a “causal” role in cognitive health, the researcher found evidence that carotenoids — natural metabolites from foods like leafy greens and fruits, which are abundant in the Mediterranean diet — may have a protective role against Alzheimer’s.
“This finding suggests that diet-derived metabolites could be part of the biological pathway linking nutrition to long-term brain health,” says Liu.
Some Experts See These Findings as a Breakthrough
Richard Isaacson, MD, an Alzheimer’s prevention specialist and director of research at the Institute for Neurodegenerative Diseases in Boca Raton, Florida, views these study results as a “breakthrough.”
“Some people with two copies of APOE4 have felt like they’re doomed,” says Dr. Isaacson, who was not involved in the research. “While the Mediterranean diet is protective against dementia for anyone, the big shocker here is that it is protective for those with [two copies of] APOE4. So this study may actually move the needle and encourage high-risk individuals to change what they eat.”
Isaacson points to several strengths in the analysis, including the long follow-up period and large participant number.
He also singled out the use of blood tests as a strength of the study. “There were actually biological markers in blood samples that could confirm whether the nutrients were having a positive effect or not,” he says.
As for study limitations, self-reported dietary habits are not always accurate, and the study population consisted primarily of health professionals of European ancestry, so findings may not be generalized to all populations.
Should You Get Tested for APOE4?
Healthcare providers usually don’t test for APOE genes, since the results can’t fully predict if someone will get Alzheimer’s. Plus, it’s not necessary for diagnosis.
“Routine testing is not currently recommended for the general population,” says Liu. “Importantly, APOE4 is a risk factor, but not a diagnosis. Many carriers never develop dementia, and many noncarriers still do. If someone is concerned about their risk, especially those with a family history of dementia, a good first step is to talk to their doctor.”
Taking Steps Toward Healthier Eating Habits
A healthy diet matters for cognitive health for everyone, according to Liu, but it may be especially important for people at higher genetic risk.
She says that a Mediterranean diet that will have the most positive health impact requires:
- Eating mostly plant-based foods such as fruits, vegetables, legumes, nuts, and whole grains, along with fish and healthy fats like olive oil.
- Limiting red and processed meats.
- Keeping alcohol intake to a minimum.
- Adding more leafy greens to meals.
- Swapping out butter for olive oil.
- Choosing fish over red meat.
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