# Cognitive impairment associated with androgen deprivation therapy for prostate cancer

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2021 · $304,178

## Abstract

Androgen deprivation therapy (ADT) is a mainstay treatment for prostate cancer. ADT has dramatically increased
survival of men with prostate cancer, with a 5-year post-diagnosis survival rate exceeding 98%. Thus, ensuring
a strong quality of life for prostate cancer survivors has become an essential component of successful treatment.
While undoubtedly a success story in terms of cancer treatment, ADT is accompanied by adverse effects,
including significant cognitive impairment that presents a serious challenge to the quality of life for prostate
cancer survivors and their families. Further, cognitive impairment associated with ADT compromises compliance,
and increases the risk of a subsequent diagnosis of Alzheimer’s Disease (AD) and related dementia. This last
observation is especially important, as prostate cancer typically afflicts older men, with a typical age of onset in
the mid-to-late 60’s, a time at which age-related cognitive impairment is often just emerging. The purpose of the
parent R01 grant with which this administrative supplement is associated is to address the mechanism by which
ADT impairs brain function and cognition, and to test a novel therapeutic intervention aimed at improving
cognition after ADT. The purpose of this administrative supplement, submitted in response to NOT-AG-20-034,
is to begin testing the interacting detrimental influences of cancer pathophysiology and ADT in producing
cognitive impairment specifically in the aging brain, and to identify potential factors that may increase the
likelihood of developing Alzheimer’s disease and related dementias, including inflammatory signaling related to
neurodegeneration, and indices of Alzheimer’s-related neuropathology in the brains of 12-mo old rats, also an
age at which age-related cognitive impairment is just starting to emerge. In aim 1, we will test the detrimental
effects of ADT on cognition, inflammatory signaling implicated in neurodegeneration, and indices of Alzheimer’s-
related neuropathology in the brains of 12-mo old male Sprague-Dawley rats, the strain we have used in this
project to date, and the newly reconstituted Copenhagen rat strain that we will use in future studies to introduce
prostate cancer. Measures will include cognitive function on the attentional set-shifting test, mediated in the
medial prefrontal cortex (mPFC), and visuospatial cognitive function on the novel object location test, mediated
in hippocampus (Hipp); measures of neuroinflammatory signaling and AD-related neuropathology in mPFC and
Hipp; and brain oxidative metabolic status, assessed by measuring NAD+ in mPFC and Hipp. In aim 2, we will
test the hypothesis that prostate cancer pathophysiology amplifies or primes the detrimental effects of ADT on
cognition, inflammatory signaling implicated in neurodegeneration, and Alzheimer’s-related neuropathology. We
will test the effects of ADTon the same measures in 12-mo old Copenhagen rats bearing prostate cancer tumors,
induced by implant...

## Key facts

- **NIH application ID:** 10287767
- **Project number:** 3R01CA224672-03S1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** David A Morilak
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $304,178
- **Award type:** 3
- **Project period:** 2018-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10287767

## Citation

> US National Institutes of Health, RePORTER application 10287767, Cognitive impairment associated with androgen deprivation therapy for prostate cancer (3R01CA224672-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10287767. Licensed CC0.

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