Teresa Jenica Filshtein1, Willa D Brenowitz1, Elizabeth Rose Mayeda2, Timothy J Hohman3, Stefan Walter4, Rich N Jones5, Fanny M Elahi6, M Maria Glymour7. 1. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA. 2. Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA. 3. Vanderbilt Memory & Alzheimer's Center, Department of Neurology and Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA. 4. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA; Hospital Universitario de Getafe, Madrid, Spain. 5. Department of Neurology, Brown University, Providence, RI, USA; Department of Psychiatry and Human Behavior, Brown University, Providence, RI, USA. 6. Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. 7. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA. Electronic address: Maria.Glymour@ucsf.edu.
Abstract
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.
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.
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