Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with an increased risk of dementia, according to a new study.

Using an informatics approach, Kevin T. Nead, MD, MPhil, of the University of Pennsylvania Perelman School of Medicine in Philadelphia, and colleagues examined ADT use and new-onset dementia in a cohort of 9272 men (average age 66.9) with PCa identified via computer-based processing of electronic medical records. The investigators had previously identified a link between ADT and Alzheimer’s disease, so for the current study, they widened their scope to include all forms of dementia, such as senile dementia, vascular dementia, frontotemporal dementia, and Alzheimer dementia. Nearly 20% of patients received ADT.

Analyses revealed a 2.17 times increased risk of dementia among ADT recipients versus non-recipients, according to findings published online ahead of print in JAMA Oncology. The association held even after exclusion of Alzheimer disease patients, who had 2.32 times greater odds. The relative risk for dementia at 5-years from ADT initiation was 7.9% among ADT recipients compared with just 3.5% in non-recipients. Patients treated with ADT for at least 12 months had the highest absolute increase in risk; they were 2.36 times more likely to experience dementia compared with patients who did not receive ADT.

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The researchers adjusted for a range of confounders, such as comorbidities, race, and age. They also analyzed a subset of patients by Gleason score and the association held. Higher risks overall were found among ADT users regardless of age. ADT recipients older than 70 were the least likely to remain dementia free, with a 7.1% absolute increase in dementia risk 5 years after ADT initiation.

“Our study extends previous work supporting an association between use of ADT and Alzheimer[‘s] disease and suggests that ADT may more broadly affect neurocognitive function,” Dr Nead and colleagues concluded.

Given the possible implications for public health, the investigators encouraged future prospective studies to investigate the relationship, including by ADT type. Among the limitations, the researchers noted that patients with cardiometabolic disorders—an important risk factor for dementia—tend to be poor candidates for prostatectomy and therefore more likely to receive radiation treatment and ADT.

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1.  Nead KT, Gaskin G, Chester C, et al. Association Between Androgen Deprivation Therapy and Risk of Dementia. JAMA Oncol. doi:10.1001/jamaoncol.2016.3662. [Epub ahead of print]

2.  Walsh CG, Johnson KB, et al. Observational Cohort Studies and the Challenges of In Silico Experiments. JAMA Oncol. doi:10.1001/jamaoncol.2016.3478. [Epub ahead of print]