Joanne M. Li, Abigail Gauen, Rachel Zmora, John J. Stephen, Lucia C. Petito, D. Scholtens, Elizabeth Peterson, Ciaran Kohli‐Lynch, Maxwell Mansolf, Sanaz Sedaghat, Katherine Giorgio, Alden L. Gross, Catherine Helmer, Stéphanie Debette, Aïcha Soumaré, M. Arfan Ikram, Frank J. Wolters, Sudha Seshadri, Claudia L. Satizabal, Jayandra Himali, Deborah A. Levine, Emily M. Briceño, Farzaneh A. Sorond, L.J. Launer, David Li, Djass Mbangdadji, Lihui Zhao, Donald M. Lloyd‐Jones, Oscar L. Lopez, Suzanne E. Judd, Timothy M. Hughes, Vilmundur Gudnason, Allison E. Aiello, Alison E. Fohner, Archana Singh‐Manoux, N Allen
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.