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

Teresa Jenica Filshtein; Willa D Brenowitz; Elizabeth Rose Mayeda; Timothy J Hohman; Stefan Walter; Rich N Jones; Fanny M Elahi; M Maria Glymour

doi:10.1016/j.jalz.2019.04.005

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

Alzheimers Dement. 2019 Jul;15(7):907-916. doi: 10.1016/j.jalz.2019.04.005.

Authors

Teresa Jenica Filshtein¹, Willa D Brenowitz¹, Elizabeth Rose Mayeda², Timothy J Hohman³, Stefan Walter⁴, Rich N Jones⁵, Fanny M Elahi⁶, M Maria Glymour⁷

Affiliations

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: [email protected].

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.

Keywords: Alzheimer's disease; Cognitive aging; Cognitive reserve; Education; Falls; Genetic risk; Genetic risk score; Hospitalization; Mortality; UTIs.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Alzheimer Disease* / genetics
Alzheimer Disease* / mortality
Cognitive Reserve / physiology*
Cohort Studies
Female
Genetic Predisposition to Disease*
Hospitalization / statistics & numerical data*
Humans
Male
Middle Aged
Mortality / trends*
Polymorphism, Single Nucleotide / genetics
Risk Factors
United Kingdom

Abstract

Publication types

MeSH terms

Grants and funding