Date of Award:

8-2026

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Psychology

Committee Chair(s)

JoAnn T. Tschanz

Committee

JoAnn T. Tschanz

Committee

Gail B. Rattinger

Committee

Mona Buhusi

Committee

M. Scott DeBerard

Committee

Sarah Schwartz

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia in individuals aged 65 years and older. There are a number of lifestyle and genetic factors that affect one’s risk for AD including traumatic brain injury (TBI), and genes such as those for Apolipoprotein E (APOE) and brain-derived neurotrophic factor (BDNF). This study examined sex differences in how TBI history influences risk for AD, exploring genetic variants suspected to play a role in TBI recovery. Additionally, in following an inflammatory mechanism in TBI, the study also determined if nonsteroidal anti-inflammatory drug (NSAID) use reduced subsequent risk for AD. The study analyzed extant data from the Cache County Study on Memory in Aging (CCSMA) and National Alzheimer’s Coordinating Center Uniform Data Set (NACC-UDS) that together consisted of 6,878 participants over the age of 65.

Among females, APOE genotype moderated the association between TBI number and AD risk whereas in males, BDNF genotype showed this effect moderation. With respect to NSAID use, females with a history of TBI and NSAID use showed a trend toward increased AD risk while those without a TBI but with NSAID use showed a trend toward lower risk. Overall, results from this study suggest sex difference in AD risk following TBI and that risk for AD may be better understood as a gene-environment interplay rather than TBI alone as the driving force for AD risk. Future research should look at how repeated brain injuries and sex-related hormonal differences interact with genetic risk factors to influence long-term cognitive outcomes and dementia risk.

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