People carrying two copies of 'Alzheimer's gene' lowered risk by 35% via diet changes

By Sandee LaMotte, CNN
(CNN) — Closely following the Mediterranean diet lowered the risk of dementia by at least 35% in people with two copies of the APOE4 gene, a major risk factor for Alzheimer’s, according to a new study.
“We followed over 5,700 people for 34 years and found those who followed a baseline Mediterranean diet with little alcohol, red and processed meat but full of vegetables, fruits, nuts, whole grains, legumes, fish and olive oil all reduced the risk of dementia,” said Yuxi Liu, lead author of the Mass General Brigham study published Monday in the journal Nature.
“But the benefit was highest for people with the APOE4 gene, especially those with two copies of APOE4,” said Liu, a research fellow in medicine at Brigham and Women’s Hospital and Harvard Medical School in Boston. “Not only did following a baseline Mediterranean diet reduce the probability of developing dementia by 35% in people with two APOE4 genes, but higher adherence to the diet further reduced their risk.”
Another major finding of the study: People with the APOE4 gene appear to have distinctive metabolic profiles that dramatically respond to healthy nutrients in the Mediterranean diet.
Metabolic processes such as nutrient digestion, energy production, and the building and repairing of nerves and tissues of the body and brain are highly dependent on the quality of vitamins, enzymes, amino acids, carbohydrates and lipids (fats) in a healthy diet, Liu said.
“Improving the metabolic function in people with APOE4 through diet might explain, or at least partially explain, the huge fall in dementia risk we saw in our study,” she said. “Of course, we need future studies to further validate that concept.”
This is a “stop the presses” finding, said neurologist Dr. Richard Isaacson, director of research at the Institute for Neurodegenerative Diseases in Florida who conducts studies on cognitive improvement in people who are genetically at risk for Alzheimer’s disease.
“Hopefully this will change the current dogma that having two copies of the APOE4 is a ‘fait accompli’ for developing Alzheimer’s,” said Isaacson, who was not involved in the study.
“Genes do not have to be your destiny,” he added. “If the risk of dementia in a person in the highest risk category can be cut by 35% just by following a specific diet, imagine what can be done when you work on dozens of modifiable risk factors such as exercise, sleep, stress and the like.”
Healthy behaviors and dementia risk
This isn’t the first study to find a link between the Mediterranean and other plant-based diets and dementia risk.
A large study of over 60,000 people in the United Kingdom in 2023 found those who stuck most closely to a Mediterranean diet had up to a 23% lower risk for dementia compared with people who didn’t follow the diet well.
Another 2023 study that looked at brain tissue echoed these findings. People who consumed foods from the plant-based Mediterranean and brain-focused MIND diets had almost 40% lower odds of having the hallmark signs of Alzheimer’s — sticky beta-amyloid plaques and tau tangles in the brain — when autopsied.
That’s not all. Adding just one food category from either diet — such as eating recommended amounts of vegetables or fruits — reduced amyloid buildup in the brain to a level similar to being about four years younger, the study found.
The MIND diet is short for Mediterranean-DASH Diet Intervention for Neurodegenerative Delay. This diet sticks to the Mediterranean diet but recommends specific amounts of known brain-healthy foods such as dark leafy greens and berries.
But it’s when individuals take lifestyle changes to the next level that the most benefit is seen, according to Isaacson. A patient in his clinical trial, Simon Nicholls, reduced his risk of developing Alzheimer’s via lifestyle changes including diet, exercise, reducing stress and optimizing sleep, along with a few strategically chosen supplements and medications. Nicholls, who has two copies of the APOE4 gene, dramatically changed his exercise and eating habits and within a year had reduced the amount of amyloid and tau in his blood.
Even more startling: Brain volume scans showed that the hippocampus, the tiny seahorse-shaped organ responsible for memory, had actually grown in volume in Nicholls’ brain since he started the intervention. Nicholls continues to maintain his healthy lifestyle and has continued to improve, Isaacson said.
Possible future loss of study data
The new study followed men and women between the ages of 55 and 75 who were part of the Nurse’s Health Study, started in 1976 to investigate women’s nutritional risk factors for chronic disease, and the Health Professionals Follow-Up Study, which has chronicled the health and diet of men since 1986.
Dietary data, along with DNA, blood, urine, stool and tissue samples from both studies, have enabled researchers like Liu to make major advances in science — the discovery of the dangers of trans fats and the subsequent ban from the US food supply; the link between obesity and breast cancer, even in adolescents; and the connection between cigarette smoking and heart disease.
However, federal funding for both studies has been stopped due to the Trump administration’s ongoing feud with Harvard University. Without that money, decades of bio samples may be discarded.
“We’re going to take 50 years of research and all this biodata and just destroy it, make it useless?” one of the nurses in the study, Martha Dodds, told CNN previously. “It’s like burning the Library of Congress — you just can’t get that back.”
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