Abstract 46: Midlife and Late-Life Population Attributable Fractions of Dementia Risk Factors in the United States: A Cohort Study From the Dementia Risk Pooling Project

Introduction: Dementia cases in the US are projected to nearly double from 5.3 million in 2019 to 10.5 million by 2050. Research has suggested that 41% of US dementia cases may be prevented by eliminating several specific modifiable risk factors. Still, few studies examine risk factor variation between midlife and late-life. Previous studies have also been limited by sample diversity and size. The Dementia Risk Pooling Project (DRPP) is a consortium of longitudinal cohorts including several underrepresented racial/ethnic groups pooled at the individual level. Methods: We estimated individual and combined population attributable fractions (PAF) for seven modifiable risk factors in midlife (aged 45-64) and late-life (aged 65+), using data from six US cohorts in DRPP. We also used potential impact fractions (PIF) to estimate dementia cases that could be prevented due to risk factor reduction in midlife and late-life based upon the National Alzheimer’s Advisory Council goal of a 15% reduction in dementia risk factors by 2030. Results: In a sample of 41,432 unique participants (ppts), risk factor exposure was measured in midlife for 29,983 ppts (60% female, 77% white) and in late-life for 30,633 ppts (56% female, 70% white). During follow-up, 4,186 midlife ppts and 4,893 late-life ppts developed dementia. We found that eliminating midlife risk factors could prevent a greater proportion of dementia cases [PAF 41.3%, 27.9%-54.6%] compared to late-life risk factors [23.1%, 12.4%-33.7%]. Midlife physical inactivity [18.8%, 15.1%-22.4%] appeared to be the greatest contributor. Late-life hypertension and depression appeared to contribute to 9.8% [5.5%-13.9%] and 4.2% [3.5%-5.0%] of cases, respectively. Given the US prevalence of dementia in 2020, we estimate that a 15% reduction in physical inactivity alone could prevent 148,339 dementia cases. Conclusion: The importance of modifiable risk factors for dementia may vary with age. These estimates could inform the timing of public health interventions for dementia prevention.