The science-backed diet that can lower dementia risk even if you have the ‘Alzheimer’s gene’

New research has found that one specific diet can help reduce the risk of Alzheimer’s disease, even for people with the highest genetic predisposition. 

Harvard University and Mass General Brigham researchers have found that eating a Mediterranean diet can powerfully slash dementia risk, offering the greatest protection to those who have the highest genetic risk for Alzheimer’s.

Alzheimer’s and other forms of dementia are leading causes of memory loss in older adults. The risk of developing Alzheimer’s is heavily influenced by genetics, which may account for up to 80 percent of a person’s likelihood of getting the disease.

But the researchers found that those who have two copies of the APOE4 gene, which makes them 10 times more likely to get Alzheimer’s, benefited most from strictly following the Mediterranean diet.

The Mediterranean diet, consisting of fish, legumes, nuts, vegetables and healthy fats, is the only diet proven in gold-standard studies to improve brain health and slow cognitive decline.

The study’s findings were drawn from an analysis of 4,215 women, tracked for over 30 years, and were subsequently validated in a separate group of 1,490 men. It was built on previous research that has found that following a regimented Mediterranean diet reduced Alzheimer’s risk by 23 percent.  

The researchers also found that people with the APOE4 gene were uniquely receptive to the Mediterranean diet compared to those with one or no copies, their bodies responding more positively to healthy foods’ nutrients.

The diet worked by changing their blood biomarkers, which accounted for about 40 percent of the diet’s total benefits, including lower inflammation, better blood vessel health, improved insulin sensitivity and decreased levels of amyloid plaques that build up in the brain and contribute to Alzheimer’s-related cognitive decline.

Dr Yuxi Liu, a research fellow in the Department of Medicine at Brigham and Women’s Hospital and the first author, said: ‘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.

‘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.’

While the team did not provide a percentage for how much the risk was lowered, they referenced the PREDIMED trial, a landmark randomized controlled trial that has shown a Mediterranean diet supplemented with extra virgin olive oil saw essentially no cognitive decline over the four-year study.  

The benefit was greatest for people who most needed the boost in protection. Researchers found that those with high genetic risk have a dysfunctional metabolism unique to them.

The APOE4 gene variant is the strongest known genetic risk factor for developing Alzheimer’s disease. It plays a crucial role in how the body metabolizes fats and cholesterol, and the E4 variant is associated with the buildup of amyloid plaques in the brain, a hallmark of Alzheimer’s pathology. 

Carrying even one copy of this gene significantly increases risk, but having two copies confers the highest likelihood of developing the disease. 

Having two copies of the APOE4 gene is rare. While 75 million Americans have one copy, 7million Americans, about two percent of the US population, have two.

Australian actor Chris Hemsworth learned while filming a National Geographic docuseries that he had inherited two copies of APOE4, dubbed ‘the Alzheimer’s gene’, from his parents.

The diagnosis prompted Hemsworth to pause his career so he could prioritize his brain health, spend more time with his family, and be more selective about his roles. 

An estimated 7million Americans have Alzheimer’s disease. The vast majority were driven by genetics.

A non-APOE carrier has about a nine percent chance of developing Alzheimer’s disease, while a person with one copy has a 30 percent risk. Two copies increase the risk to about 90 percent. 

Their blood showed unhealthy levels of lipids and other metabolites that promote inflammation and brain damage.

The eating plan study subjects followed was a combination of the Mediterranean diet and the heart-healthy DASH diet, which encourages people to eat similar foods but with stricter guidelines and portion control measures designed to lower blood pressure.

Researchers found that the diet corrected some markers of dysfunction in the way the body processed sugars and fats, and actively improved the body’s chemistry that influences brain health. 

It boosted levels of beneficial fats and protective, natural compounds, including those found in black pepper, leafy greens and whole grains, while reducing harmful fats, which support cognitive function.

Their research was built on two major, sweeping prospective studies: the Nurses’ Health Study, which began in 1976 and enrolled 121,700 female registered nurses aged 30 to 55, and the Health Professionals Follow-Up Study, which started in 1986 and enrolled 51,529 male health professionals aged 40 to 75.

Detailed food frequency questionnaires were mailed to participants every two to four years, asking people to report how often they consumed specific foods and beverages.

Researchers behind the time-spanning studies validated the questionnaires against food diaries and blood tests, ensuring the data was accurate and reflective of people’s eating patterns.

A subset of older participants underwent cognitive tests over the phone every two years. 

Researchers measured memory, attention, and verbal fluency using standardized tools like the Telephone Interview for Cognitive Status (TICS).

Researchers identified new dementia cases by recording when participants reported a diagnosis on their regular questionnaires or when it was listed on a death certificate.

A team of medical experts then reviewed each study subject’s complete medical records, without prior knowledge of their other study data, to confirm the diagnosis against modern medical standards.

And to gather people’s genetic data, researchers analyzed blood samples collected and stored from participants over decades. 

Genotyping identified each person’s genetic risk factors, including the APOE4 gene, while advanced blood analysis measured hundreds of blood biomarkers.

Dr Yuxi Liu, the first author of the study and a research fellow in the Department of Medicine at Brigham and Women’s Hospital, said: ‘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.

‘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.’

The latest research was published in the journal Nature Medicine.