# Effects of Androgen Deprivation Therapy on Preclinical Symptoms of Alzheimer's Disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $631,855

## Abstract

PROJECT SUMMARY
Low levels of testosterone in older men have been associated with an increased risk of developing Alzheimer's
disease (AlzD). Declines in testosterone begin as early as the mid-thirties, and by late-middle age contribute
to many of the physiological and psychological complaints associated with male aging. The timing of these
changes overlaps with the preclinical stage of AlzD, a period that has been targeted as the optimal time during
which interventions for the disease may have the greatest effect. The degree to which declines in testosterone
influence the preclinical markers of AlzD – cognition, beta-amyloid (Aβ), and tau – represents a significant
knowledge gap that has yet to be adequately examined. In the proposed study we will examine cognitively
normal men undergoing androgen deprivation therapy (ADT) for non-metastatic prostate cancer, as well as a
non-ADT prostate cancer positive control group, with the goal of clarifying the effects of testosterone depletion
on preclinical markers of AlzD. ADT is a commonly used treatment for prostate cancer, and offers a unique
scenario through which to study the impact of dramatic testosterone depletion on the preclinical markers of
AlzD. Although ADT is an effective cancer treatment, it is associated with a wide variety of side effects,
including an increased risk for AlzD. In Aim 1, we will characterize the effects of ADT on cognitive function.
We will assess an array of cognitive tests, and utilize a well validated measure of cognitive effort, task-evoked
pupil dilation, to assess cognitive changes brought on by ADT. We hypothesize that ADT will tax cognitive
resources, resulting in changes in effort and performance. In Aim 2, we will test whether the polygenic risk for
AlzD alters the effects of ADT on cognition. We hypothesize that changes in AlzD sensitive cognitive abilities
will be greater in individuals at greater genetic risk for AD. In Aim 3, will determine the extent to which
measures of Aβ and tau are influenced by ADT. We will utilize gold standard CSF based measures, and
neuronally-derived exosomes from plasma to acquire levels of Aβ40, Aβ42, total-tau, and phosphorylated-tau.
We hypothesize that over the course of ADT we will observe significant changes in Aβ and tau levels, and that
these changes will be more pronounced in those at greater genetic risk for AlzD. Moreover, we hypothesize
that changes in Aβ and tau will be more strongly correlated with cognitive performance and cognitive effort in
those at greater genetic risk for AlzD. Assessments will be conducted pre-treatment, and then again at 6 and
12 month follow-ups (three assessments in total). This naturalistic study of a unique clinical population offers a
valuable opportunity to examine the impact of changes in a single AlzD risk factor (testosterone level). In
contrast to the years or decades that it might take for clinically significant declines in testosterone to manifest in
standard populations, we will b...

## Key facts

- **NIH application ID:** 10176322
- **Project number:** 5R01AG056410-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Matthew S Panizzon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $631,855
- **Award type:** 5
- **Project period:** 2017-07-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176322

## Citation

> US National Institutes of Health, RePORTER application 10176322, Effects of Androgen Deprivation Therapy on Preclinical Symptoms of Alzheimer's Disease (5R01AG056410-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10176322. Licensed CC0.

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