Favorable Lifestyle Factors Reduce Dementia Risk Across Key Genetic Profiles, Japanese Study Finds
核心洞察
A Kyushu University and RIKEN (搜索) study of 9,605 Japanese adults aged 65+ found that favorable modifiable risk factors significantly lower dementia (搜索) risk in individuals with zero or one APOE ε4 (搜索) allele.
Individuals carrying two APOE ε4 (搜索) alleles (homozygotes) had over 10-fold higher dementia (搜索) risk than noncarriers, and lifestyle modifications did not significantly alter their risk.
Brain MRI scans showed less brain atrophy and fewer white matter lesions in those with lower modifiable risk scores among one-or-no-allele carriers, but not in two-allele carriers.
A new study from Kyushu University and RIKEN (搜索), published on May 21 in Alzheimer's & Dementia (搜索): Diagnosis, Assessment & Disease Monitoring, provides critical insights into the interplay between genetic susceptibility and lifestyle factors in dementia risk. Analyzing data from 9,605 community-dwelling Japanese adults aged 65 and older, the research demonstrates that favorable modifiable risk factors (mRF)—behaviors or conditions that individuals can change or control—can significantly reduce dementia risk, but with important distinctions across genetic profiles.
The study determined each participant's APOE ε4 (搜索) genotype, the primary genetic risk factor for Alzheimer's disease (搜索), and calculated an mRF score based on lifestyle and health-related factors. This dual assessment allowed researchers to evaluate how genetic predisposition and lifestyle choices jointly influence dementia (搜索) risk.
Genetic Risk Stratification Reveals Stark Differences
The results showed that dementia (搜索) risk rose progressively with the number of APOE ε4 (搜索) 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.
Among individuals with one or no APOE ε4 (搜索) alleles, maintaining a healthier profile with lower mRF scores was linked to a significantly lower risk of dementia (搜索). In contrast, among individuals with two APOE ε4 alleles, dementia risk did not differ significantly between those with lower and higher mRF scores.
Neuroimaging Evidence Supports Clinical Findings
Brain MRI scans reinforced these observations. Among those with one or no APOE ε4 (搜索) alleles, lower mRF scores were associated with less brain atrophy and fewer white matter lesions—areas of damaged tissue in the brain linked to cognitive decline and dementia (搜索). Conversely, individuals with two APOE ε4 alleles exhibited greater brain atrophy and more extensive tissue damage regardless of their lifestyle profile.
Implications for Prevention Strategies
"Among individuals carrying one APOE ε4 (搜索) allele, as in those carrying no APOE ε4 alleles, favorable management of risk factors may help reduce the risk of dementia (搜索)," said 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."
These findings underscore the importance of population-based prevention strategies focused on managing vascular and lifestyle risk factors, while also highlighting the need for targeted therapeutic development for those at highest genetic risk.
The study contributes to a growing body of evidence that lifestyle interventions can meaningfully influence dementia (搜索) trajectories. A 2020 study from Rush University in Chicago found that stacking four to five healthy lifestyle factors could lower dementia risk by as much as 60 percent compared to people with zero to one of those factors. Dr. Klodian Dhana, an associate professor and epidemiologist at Rush who co-authored that research, noted: "APOE4 is a well-recognised and strong genetic risk factor for dementia. We demonstrated that a healthy lifestyle may still be associated with a slower rate of cognitive decline even among APOE4 carriers."
The 2024 Lancet Commission report further concluded that "evidence is increasing and is now stronger than before that tackling the many risk factors… reduces the risk of developing dementia (搜索)," listing well-established factors including lower education, hearing loss, hypertension, smoking, obesity, depression, physical inactivity, diabetes, excessive alcohol consumption, traumatic brain injury, air pollution, social isolation, untreated vision loss, and high LDL cholesterol.
With dementia (搜索) cases expected to nearly triple worldwide by 2050, the Kyushu University and RIKEN (搜索) findings offer a nuanced roadmap: for the majority of the population, lifestyle modification remains a powerful tool for risk reduction, while those with the highest genetic vulnerability require distinct, earlier, and potentially novel interventions.