Midlife and late-life population attributable fractions of risk factors for dementia in the United States: The Dementia Risk Prediction Project.

INTRODUCTION: Dementia prevalence is associated with modifiable factors. We quantified the contribution of dementia risk factors in midlife (45-64 years) and late life (≥ 65 years) in the United States. METHODS: Data from six community-based cohorts in the Dementia Risk Prediction Project (DRPP) were used. We estimated risk factor prevalence using nationally representative data. Cohort-specific Cox regression models were used to estimate the association between modifiable risk factors and incident dementia in midlife and late life. Hazard ratios were pooled using meta-analysis then used to calculate population attributable fractions (PAFs) and potential impact fractions. RESULTS: Midlife and late-life risk factors contributed to 22.7% and 16.5% of total dementia cases, respectively. Midlife obesity (PAF: 7.7%; 95% confidence interval [CI]: 4.9%-10.5%), lower education (PAF: 8.1%; 95% CI: 5.2%-11.1%), and late-life physical inactivity (PAF: 10.4%; 95% CI: 6.2%-14.5%) were the greatest contributors. DISCUSSION: Midlife and late-life modifiable risk factors contribute to dementia risk, highlighting a need for interventions across the life course. HIGHLIGHTS: Our sample included 37,931 participants across six pooled, longitudinal US cohorts. We observed midlife and late-life risk factors contributed to 22.7% and 16.5% of dementia cases, respectively. Midlife obesity, late-life physical inactivity, and lower education appear to be the greatest contributors to dementia risk.