Graduation Date

Spring 5-7-2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Medical Sciences Interdepartmental Area

First Advisor

Diane K Ehlers, PhD

MeSH Headings

prostate cancer, physical activity, cognition, frailty

Abstract

Prostate cancer (PCa) treatment often leads to distressing side effects ranging from muscle loss, physical inactivity, and fatigue to cancer associated cognitive decline (CACD). Evidence suggests that men treated with androgen deprivation therapy (ADT) may have a specifically high risk of CACD, partially due to increased frailty. However, the current literature on cognitive effects of ADT is equivocal. Therefore, the primary objectives of this study were to (1) compare cognitive function, physical activity (PA), and fitness in men receiving ADT, men scheduled to receive radiation, and men under active surveillance for PCa; (2) examine changes in cognitive performance and PA across radiation treatment; (3) explore correlations between changes in frailty markers and cognitive performance at follow-up; and (4) propose a treatment to ameliorate cognitive decline in PCa survivors treated with ADT. To accomplish these aims, men (N = 114, M age = 65.35 ± 7.71 years) completed cognitive tests, actigraphy, hand grip dynamometry, and questionnaires assessing PA, symptom burden, and quality of life prior to radiation therapy, immediately post radiation, and 30-days post radiation. A subsample of men (n = 17) also completed a maximal cardiopulmonary exercise test at baseline. Men treated with ADT exhibited significantly worse verbal memory speed compared to men under active surveillance; however, no other between group differences in cognitive performance, PA, or fitness were observed. PCa treatment did not lead to declines in cognitive function or PA. There was, however, a significant group*time interaction on executive function accuracy. While men receiving only radiation improved executive function accuracy across treatment, men treated with ADT did not. Changes in moderate-to-vigorous PA and fatigue were significantly associated with cognitive performance; however, directionality of the relationship depended on the domain assessed. Overall, findings from this study indicate that men treated with ADT may experience subtle cognitive changes relative to memory encoding shortly after treatment initiation. Declines may be associated with PA and fatigue; however, additional research is needed to understand these mechanisms. Additionally, data presented here, combined with current literature, indicate that exercise interventions, particularly resistance training may be an effective strategy for ameliorating CACD among PCa survivors.

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