Reserve and Alzheimer's disease genetic risk: Effects on hospitalization and mortality

Introduction: Cognitive reserve predicts delayed diagnosis of Alzheimer's disease (AD) and faster postdiagnosis decline. The net impact of cognitive reserve, combining both prediagnosis and postdiagnosis risk, on adverse AD-related outcomes is unknown. We adopted a novel approach, using AD genetic risk scores (AD-GRS), to evaluate this. Methods: Using 242,959 UK Biobank participants age 56+ years, we evaluated whether cognitive reserve (operationalized as education) modified associations between AD-GRS and mortality or hospitalization (total count, fall-related, and urinary tract infection–related). Results: AD-GRS predicted mortality and hospitalization outcomes. Education did not modify AD-GRS effects on mortality, but had a nonsignificantly (interaction P =.10) worse effect on hospitalizations due to urinary tract infection or falls among low education (OR = 1.07 [95% CI: 1.02, 1.12]) than high education (OR = 1.01 [0.95, 1.07]) individuals. Discussion: Education did not convey differential survival advantages to individuals with higher genetic risk of AD, but may reduce hospitalization risk associated with AD genetic risk.