With dementia cases projected to nearly triple worldwide by 2050, researchers are increasingly seeking ways to prevent or delay the disease. While genetics play a major role in determining dementia risk, lifestyle and health-related factors such as physical activity, smoking, and blood pressure management are also known to influence brain health. However, it has remained unclear whether healthy lifestyle habits provide the same protective effects for people with different levels of genetic susceptibility.
A new study led by researchers from Kyushu University and RIKEN examined whether favourable modifiable risk factors, or mRFs, could reduce dementia risk even among individuals with a strong inherited predisposition. Published in the journal Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, the study explored how lifestyle and genetics jointly influence dementia development in later life.
The research team analysed data from 9,605 community-dwelling Japanese adults aged 65 and older. Each participant underwent genetic testing to determine their APOE ε4 status, the strongest known genetic risk factor for Alzheimer’s disease. People inherit one copy of the APOE gene from each parent, meaning they may carry zero, one, or two APOE ε4 alleles. Researchers also calculated an mRF score for each participant using lifestyle and health-related measures, allowing them to compare dementia risk across different genetic and lifestyle profiles.
The findings showed that dementia risk increased steadily with the number of APOE ε4 alleles carried. Individuals with two APOE ε4 alleles, known as homozygotes, had more than a tenfold higher risk of dementia compared with noncarriers. However, among people carrying one or no APOE ε4 alleles, healthier lifestyles and vascular risk profiles were associated with significantly lower dementia risk. In contrast, among individuals carrying two APOE ε4 alleles, dementia risk remained high regardless of whether their lifestyle profile was favourable or unfavourable.
Brain MRI findings supported these results. Participants with one or no APOE ε4 alleles and lower mRF scores showed less brain atrophy and fewer white matter lesions, both of which are associated with cognitive decline and dementia. Meanwhile, individuals carrying two APOE ε4 alleles demonstrated greater brain shrinkage and more extensive tissue damage irrespective of lifestyle or health status, suggesting that genetic effects may outweigh the benefits of lifestyle management in this high-risk group.
According to Professor Toshiharu Ninomiya, the study highlights the importance of population-based prevention strategies targeting vascular and lifestyle risk factors. The findings suggest that maintaining favourable health behaviours may substantially reduce dementia risk for many people, including those carrying a single APOE ε4 allele. At the same time, the researchers note that individuals carrying two APOE ε4 alleles may require earlier intervention and additional preventive or therapeutic approaches beyond lifestyle and health management alone.
More information: Masaya Kumamoto et al, APOE ε4, modifiable risk factors, and dementia in community-based older Japanese adults, Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. DOI: 10.1002/dad2.70371
Journal information: Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring Provided by Kyushu University
