Population Attributable Fractions Associated with Alzheimer’s Disease Risk Factors

Abstract Although numerous risk factors for Alzheimer’s disease (AD) and related dementias (ADRD) have been identified, their combined influence on risk remains uncertain. In this study, we leverage a high-power 5%-sample of the Medicare population to assess the joint impact of AD/ADRD risk-related diseases and low income—as indicated by dual Medicare eligibility—on the risk of clinical diagnosis of AD/ADRD. We leveraged the univariable and multivariable Cox models for estimating AD/ADRD risks, identified most powerful predictors, and constructed predictive multivariable models for AD/ADRD risks, and evaluated their population attributable fractions (PAFs) for the general populations of older adults and race- and sex-specific subpopulations. The identified model included nine diseases—heart failure, hypertension, arrhythmia, stroke, hypotension, renal disease, depression, traumatic brain injury, and diabetes mellitus—as primary determinants of variation in AD/ADRD risk. The fraction of the total PAF explained by the predictors increased with age. The decomposition of the total PAF in terms of disease-specific PAFs showed that hypertension, stroke, and depression provided the strongest contribution for all subpopulations: Hypertension reached 45-50% of total PAF for Black, Asian, and Hispanic subpopulations. Stroke was the primary contributor for males (>30%); depression was highest among females and White individuals (approximately 30%). Hypertension and depression were the leading contributors for Native Americans (both approximately 30%). Heart Failure was the fourth strongest contributor for all subpopulations, with the contribution exceeding 5% for Native American individuals. Additional noteworthy contributors with PAFs exceeding 3% included hypotension (males), diabetes (Asian, Hispanic), arrhythmia (males), and TBI (Black, Asian).