Predicting Cognitive Decline From Androgen Deprivation Therapy

Description

Androgen Deprivation Therapy (ADT) is associated with cognitive impairment and dementia in men with prostate cancer. Pre-clinical data suggest that ADT-induced hypogonadism leads to accumulation of beta-amyloid plaques in the hippocampus, a pathological hallmark of Alzheimer's Disease (AD). Neuroimaging Functional magnetic resonance imaging (fMRI) studies also demonstrate that ADT decreases metabolic activity in the parietal, occipital, and prefrontal cortices. Multiple prospective cohort and population-based clinical studies have been conducted to test the association between ADT and cognitive impairment and/or dementia. Plasma biomarkers have been developed to predict brain amyloidosis, a key pathological feature of AD and a risk factor for developing dementia due to AD. The advantage of a blood-based assay is the lower cost, invasiveness, and time compared to cerebrospinal fluid (CSF) and Positron Emission Tomography (PET)-based biomarkers.

Conditions

Prostate Cancer

Study Overview

Study Details

Study overview

Androgen Deprivation Therapy (ADT) is associated with cognitive impairment and dementia in men with prostate cancer. Pre-clinical data suggest that ADT-induced hypogonadism leads to accumulation of beta-amyloid plaques in the hippocampus, a pathological hallmark of Alzheimer's Disease (AD). Neuroimaging Functional magnetic resonance imaging (fMRI) studies also demonstrate that ADT decreases metabolic activity in the parietal, occipital, and prefrontal cortices. Multiple prospective cohort and population-based clinical studies have been conducted to test the association between ADT and cognitive impairment and/or dementia. Plasma biomarkers have been developed to predict brain amyloidosis, a key pathological feature of AD and a risk factor for developing dementia due to AD. The advantage of a blood-based assay is the lower cost, invasiveness, and time compared to cerebrospinal fluid (CSF) and Positron Emission Tomography (PET)-based biomarkers.

Plasma Amyloid-beta 42/40 to Predict Cognitive Decline From Androgen Deprivation Therapy in Prostate Cancer: a Prospective Observational Study

Predicting Cognitive Decline From Androgen Deprivation Therapy

Condition
Prostate Cancer
Intervention / Treatment

-

Contacts and Locations

San Francisco

University of California, San Francisco, San Francisco, California, United States, 94143

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * Age 18 years or greater.
  • * Fluent in reading, listening to, and writing English.
  • * Current or prior diagnosis of prostate adenocarcinoma based on a pathology report or as documented in a medical oncology, urology, or radiation oncology note.
  • * Access and ability to use a computer or mobile device with Internet connectivity to complete study procedures.
  • * Telephone Montreal Cognitive Assessment (T-MoCA) of 16 or greater.
  • * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (documented within past 3 months, otherwise patient-reported).
  • * Age 18 years or greater
  • * Fluent in reading, listening to, and writing English
  • * Identified by patient participant as a person who knows patient participant well, like a friend, family member or spouse.
  • * Access and ability to use a computer or mobile device with internet connectivity to complete study procedures.
  • * Anticipated to start ADT, which includes one of the following two treatments
  • * Gonadotropin-releasing hormone (GnRH) agonist (e.g., leuprolide, goserelin, and others).
  • * GnRH antagonist (i.e., degarelix or relugolix).
  • * Anticipated to remain on ADT for at least 12 months.
  • * Concurrent first-generation anti-androgens (e.g., bicalutamide, flutamide, nilutamide) and novel androgen-signaling inhibitors (e.g., abiraterone, enzalutamide, and apalutamide) are allowed.
  • * Concurrent radiation is allowed.
  • * Has completed definitive local therapy (radical prostatectomy or radiation therapy) for localized prostate cancer at least 6 months prior to screening.
  • * For radical prostatectomy: undetectable prostate-specific antigen (PSA) within 12 months of screening.
  • * For radiation therapy: last PSA of \< 2.0 within 12 months of screening.
  • * Small cell prostate carcinoma (pure or mixed).
  • * Receipt of ADT (GnRH agonist, GnRH antagonist, 1st-generation anti-androgen, or novel androgen signaling inhibitor) within 6 months before screening. ADT \>6 months prior to screening is allowed provided testosterone has recovered to 100 ng/ml or greater.
  • * Concurrent or anticipated (at any point during first 12 months of ADT) non-hormonal, antineoplastic systemic therapy, such as chemotherapy.
  • * Testosterone \<100 ng/ml.
  • * Prior or concurrent brain metastases (no prior or screening imaging is required).
  • * Major neurocognitive or psychiatric disorders, such as dementia or schizophrenia.
  • * Prior or concurrent malignancy other than prostate cancer whose natural history or treatment has the potential to interfere with study assessments.
  • * None.
  • * None.
  • * Any prior, concurrent, or anticipated use of any hormonal systemic therapy, including GnRH agonist, GnRH antagonist, 1st-generation anti-androgen, or novel androgen signaling inhibitor.
  • * Any known or prior history of M1 prostate cancer (no screening imaging required).
  • * Current or prior biochemical recurrence following American Urological Association guidelines for radical prostatectomy or American Society for Therapeutic Radiology and Oncology (ASTRO) guidelines for radiation therapy.

Ages Eligible for Study

18 Years to

Sexes Eligible for Study

MALE

Accepts Healthy Volunteers

No

Collaborators and Investigators

University of California, San Francisco,

Daniel Kwon, MD, PRINCIPAL_INVESTIGATOR, University of California, San Francisco

Study Record Dates

2026-05-31