Article Impact Level: HIGH Data Quality: STRONG Summary of JAMA Neurology. https://doi.org/10.1001/jamaneurol.2025.1495 Dr. Jason R. Smith et al. JAMA Neurology. https://doi.org/10.1001/jamaneurol.2025.1493 Dr. Roch A. Nianogo et al.
Points
- A prospective cohort analysis of the ARIC study followed over 12,000 participants for 33 years to quantify dementia risk from hypertension, diabetes, and smoking measured in midlife.
- Researchers determined that 21.8% of dementia cases by age 80 were attributable to vascular risk factors present in participants who were aged between 45 and 54 years.
- This attributable risk fraction increased significantly to 44.0% when the same vascular risk factors were measured in participants between the ages of 65 and 74.
- Subgroup analyses revealed even higher attributable risk in APOE ε4 noncarriers, Black and female participants, with risk fractions ranging from 25.5% up to 61.4%.
- These findings suggest that maintaining optimal vascular health across the life course could substantially mitigate a large proportion of dementia risk for individuals before they reach the age of 80.
Summary
This prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study quantified the proportion of incident dementia attributable to modifiable vascular risk factors. The analysis included up to 12,274 self-identified Black and White participants with 33 years of follow-up (1987-2020), assessing the impact of hypertension, diabetes, and current smoking. Participants were categorized into three cohorts based on their age at risk factor measurement: 45-54 years (n=7,731), 55-64 years (n=12,274), and 65-74 years (n=6,787). The primary outcome was incident dementia, with population attributable fractions (PAFs) estimated for dementia occurrence by age 80.
The study found a direct correlation between the timing of risk factor measurement and attributable risk. The PAF for dementia by age 80 was 21.8% (95% CI, 14.3%-29.3%) for risk factors measured at ages 45-54, increasing to 26.4% (95% CI, 19.1%-33.6%) when measured at ages 55-64, and rising to 44.0% (95% CI, 30.9%-57.2%) when measured at ages 65-74. In contrast, for dementia cases occurring after age 80, these risk factors accounted for a much smaller fraction, ranging from only 2% to 8%.
Subgroup analyses revealed significantly higher attributable fractions in specific populations. Among apolipoprotein ε4 (APOE ε4) noncarriers, the PAF for risk factors measured at age 55 or older ranged from 33.3% to 61.4%. For Black participants, the PAF for risk factors measured at age 45 or older was 25.5% to 52.9%; for female participants, it was 29.2% to 51.3% for risk factors measured at age 55 or older. The authors concluded that assuming causal relationships, maintaining optimal vascular health from midlife into late life could substantially mitigate a sizeable proportion of dementia risk before age 80.
Link to the article: https://jamanetwork.com/journals/jamaneurology/article-abstract/2834600
Editorial comment: https://jamanetwork.com/journals/jamaneurology/article-abstract/2834605
References Nianogo, R. A., & Barnes, D. E. (2025). Targeting vascular risk factors to reduce dementia risk. JAMA Neurology. https://doi.org/10.1001/jamaneurol.2025.1493 Smith, J. R., Pike, J. R., Gottesman, R. F., Knopman, D. S., Lutsey, P. L., Palta, P., Windham, B. G., Selvin, E., Szklo, M., Bandeen-Roche, K. J., Coresh, J., Sharrett, A. R., Gross, A. L., & Deal, J. A. (2025). Contribution of modifiable midlife and late-life vascular risk factors to incident dementia. JAMA Neurology. https://doi.org/10.1001/jamaneurol.2025.1495
