Fukuoka, Japan —With dementia cases expected to nearly triple worldwide by 2050, researchers are increasingly focused on identifying ways to prevent or delay the disease. While lifestyle and health-related factors, such as blood pressure control and physical activity, influence dementia risk, genetics also play a major role. Currently, it is unclear if maintaining a favorable lifestyle reduces dementia risk equally across different genetic backgrounds.
A new study led by Kyushu University and RIKEN, published on May 21 in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring , examines whether favorable modifiable risk factors (mRF)—behaviors or conditions that people can change or control—can lower dementia risk even among individuals with high genetic susceptibility.
To explore this, the researchers analyzed data from 9,605 community-dwelling Japanese adults aged 65 and older. They determined each participant's APOE ε4 genotypes, a primary genetic risk factor for Alzheimer's disease, and calculated the mRF score based on lifestyle and health-related factors. This allowed the team to evaluate how genetic predisposition and lifestyle choices jointly interact to influence dementia risk.
The results showed that dementia risk rose progressively with the number of APOE ε4 alleles. Since humans inherit one allele of each gene from each parent, a person can carry zero, one, or two APOE ε4 alleles. Individuals carrying two alleles, known as homozygotes, had over 10-fold higher dementia risk than noncarriers.
Notably, among individuals with one or no APOE ε4 alleles, maintaining a healthier profile with lower mRF scores was linked to a significantly lower risk of dementia. In contrast, among individuals with two APOE ε4 alleles, dementia risk did not differ significantly between those with lower and higher mRF scores.
Brain MRI scans supported these findings. Among those with one or no alleles of the gene, lower mRF scores were associated with less brain atrophy and fewer white matter lesions—areas of damaged tissue in the brain that are linked to cognitive decline and dementia. In contrast, individuals with two alleles of the gene exhibited greater brain atrophy and more extensive tissue damage regardless of their lifestyle profile.
These findings suggest that maintaining favorable lifestyle and health conditions can effectively mitigate dementia risk, even among individuals carrying a single APOE ε4 allele. This underscores the importance of population-based prevention strategies focused on managing vascular and lifestyle risk factors.
“Among individuals carrying one APOE ε4 allele, as in those carrying no APOE ε4 alleles, favorable management of risk factors may help reduce the risk of dementia,” says Professor Toshiharu Ninomiya from Kyushu University’s Faculty of Medical Sciences , who led the study. “On the other hand, for individuals carrying two APOE ε4 alleles, earlier intervention as well as new preventive or therapeutic approaches beyond lifestyle and health management may warrant consideration.”
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For more information about this research, see “APOE ε4, modifiable risk factors and dementia in community-based older Japanese adults,” Masaya Kumamoto, Toshiharu Ninomiya, Yoshihiko Furuta, Mao Shibata, Tomoyuki Ohara, Jun Hata, Tetsuro Ago, Yasuyuki Taki, Tatsuya Mikami, Tetsuya Maeda, Kenjiro Ono, Masaru Mimura, Ritsuko Hanajima, Jun-ichi Iga, Minoru Takebayashi, Yukihide Momozawa, on behalf of the Japan Prospective Studies for Aging and Dementia (JPSC-AD) Study Group. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring , https://doi.org/10.1002/dad2.70371
About Kyushu University
Founded in 1911, Kyushu University is one of Japan's leading research-oriented institutes of higher education, consistently ranking as one of the top ten Japanese universities in the Times Higher Education World University Rankings and the QS World Rankings. The university is one of the seven national universities in Japan, located in Fukuoka, on the island of Kyushu—the most southwestern of Japan’s four main islands with a population and land size slightly larger than Belgium. Kyushu U’s multiple campuses—home to around 19,000 students and 8000 faculty and staff—are located around Fukuoka City, a coastal metropolis that is frequently ranked among the world's most livable cities and historically known as Japan's gateway to Asia. Through its VISION 2030 , Kyushu U will “drive social change with integrative knowledge.” By fusing the spectrum of knowledge, from the humanities and arts to engineering and medical sciences, Kyushu U will strengthen its research in the key areas of decarbonization, medicine and health, and environment and food, to tackle society’s most pressing issues.
Data/statistical analysis
People
APOE ε4, modifiable risk factors and dementia in community-based older Japanese adults
21-May-2026
Toshiharu Ninomiya reports receiving grants from Suntory Holdings Limited. The other authors have nothing to disclose.