The objective of this study is to compare changes in neurocognitive function across a 12-month period between three groups: (1) men treated with androgen deprivation therapy (ADT) for prostate cancer (PCa); (2) men under active surveillance for PCa; and (3) men without a history of cancer.

Aim 1: This study will examine differences in neurocognitive function (cognitive performance, brain structural integrity) from baseline (within 30 days of ADT initiation or 90 days of diagnosis) to 6- and 12-month follow-up.

Aim 2: Examine group differences in components of frailty (e.g., lean mass, muscle strength, physical function, fatigue, physical activity) from baseline to 6- and 12-month follow-up.

Men will be recruited for this study if they are (1) recently diagnosed with PCa and scheduled to receive 6-months or more of ADT (ADT+ group, n=20), (2) recently diagnosed with PCa and under active surveillance (ADT- group, n=20), or (3) healthy men without a history of cancer (PCa- group, n=20). Eligible men (N=60) will be scheduled for two or three testing appointments at each testing timepoint. To assess Aim 1, participants will complete measures at baseline (M0), 6-month follow-up (M6), and 12-month follow-up (M12). Aim 1 measures include: neurocognitive tasks, functional magnetic resonance imaging (optional; n=10 ADT+ and n=10 ADT- only), and questionnaires. To assess Aim 2, outcomes indicated as components of frailty syndrome will be measured, including: dual-energy X-ray absorptiometry (e.g., appendicular lean mass), upper and lower body dynamometry, physical function and functional capacity, questionnaires (i.e., fatigue surveys), and physical activity monitoring (i.e., accelerometry). Findings from this study will build upon the scientific framework for the potential frailty pathway of cancer-associated cognitive decline in PCa patients in order to develop future evidence-based interventions to manage cognitive impairment in men diagnosed with PCa.

Inclusion Criteria:

• Telephone Interview of Cognitive Status (TICS-M) performance above impaired range (≥21)

Group-specific criteria:

• First time, primary diagnosis of prostate cancer (ADT+ and ADT-)
• Diagnosed within past 30 days (ADT-)
• Scheduled to receive ≥ 6-months androgen deprivation therapy and have not received >30 days of androgen deprivation therapy (ADT+)
• Men without a history of cancer who are within one year of age of ADT+ participants (PCa-)

Exclusion Criteria:

• Second cancer diagnosis (excluding non-invasive skin cancers)
• History of stroke, transient ischemic attack, neurological disorder, or brain surgery involving tissue removal
• Unable to walk without assistance
• Unwilling to complete study requirements
• Body weight greater than 300 pounds (DXA requirement)
• Moderate-intensity physical activity ≥ 150 minutes per week
• Upper and lower body strength training ≥ 2 days per week
• Unable to read in English

Men aged 19 years and older diagnosed with prostate cancer either under active surveillance or scheduled to receive/within 30 days of receiving androgen deprivation therapy; and age-matched men without a history of cancer.

The final dataset will not include identifying information; however, there is still a possibility of deductive disclosure of identity. Therefore, data will not be a shared via an NIH or approved public repository. We will share de-identified as required for publication in scientific journals and with outside collaborators and scientists upon request.

Data will be shared via scientific journals at the time of publication and with outside collaborators before publication.

We will make data available to researchers who agree to use the data only for research purposes, protect the data using secure computer technologies, and destroy the data after relevant analyses are completed and manuscripts are published.