Plasma Amyloid-beta 42/40 to Predict Cognitive Decline From Androgen Deprivation Therapy in Prostate Cancer: a Prospective Observational Study
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.
∙ Patient Participants-
• 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).
∙ Study partner participants-
• 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.
∙ Only the ADT cohort-
• 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.
∙ Only the PC cohort-
• 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.