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 post-diagnosis 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. (C) 2019 Published by Elsevier Inc. on behalf of the Alzheimer's Association.