Men on androgen deprivation therapy at risk of dementia, Alzheimer’s disease

Androgen deprivation therapy (ADT) in men with prostate cancer increases the risk of dementia and Alzheimer’s disease, reveals a recent study. Such risk further increases when said treatment is given for more than 12 months.

“Based on these findings, we recommend routine monitoring of cognitive function in patients receiving ADT,” the researchers said. “In addition, mental/cognitive status assessment should be performed in all patients planned for ADT.”

A systematic review and meta-analysis was performed on studies assessing the differential incidence of dementia and/or Alzheimer’s disease as outcomes in patients with prostate cancer who did versus did not receive ADT. PubMed and Web of Science databases were searched from 1 to 3 January 2020.

Random or fixed effects meta-analytic models were used in the presence of absence of heterogeneity per the I² statistic. Six meta-analyses were conducted for all-cause dementia, Alzheimer’s disease, and all-cause dementia or Alzheimer’s disease according to the duration of ADT (up to or >12 months).

Fourteen studies met the eligibility criteria, of which nine reported all-cause dementia, with eight reporting Alzheimer’s disease. Five studies evaluated these outcomes according to the duration of ADT. [J Urol 2021;205:60-67]

Patients with prostate cancer who received ADT had a higher risk of new-onset dementia (hazard ratio [HR], 1.21, 95 percent confidence interval [CI], 1.11–1.33) and Alzheimer’s disease (HR, 1.16, 95 percent CI, 1.09–1.24) than those who did not receive ADT. Dementia risk was also higher in prostate cancer patients who received ADT for >12 months, but the difference was statistically nonsignificant for <12 months of ADT exposure (HR, 1.06, 95 percent CI, 0.77–1.28).

Notably, no association was found between ADT duration and risk of Alzheimer’s disease (HR, 1.21, 95 percent CI, 0.97–1.51 for exposure up to 12 months; HR, 1.39, 95 percent CI, 0.69–2.79 for exposure >12 months).

Several studies have examined ADT duration as a risk factor for dementia and Alzheimer’s disease. Despite discrepancies in the definition of duration cutoff time within published studies, results were consistent as regards the increased risk in patients who received ADT for a longer duration. [Prostate Cancer Prostatic Dis 2018;21:403-410; Prostate Cancer Prostatic Dis 2020;23:410-418; Cancer Res Treat 2019;51:593-602; JAMA Oncol 2018;4:1616-1617; J Clin Oncol 2017;35:201-207]

“Adequate patient counseling about these potential side effects of ADT should be part of the decision making and follow-up strategy. However, prospective studies need to strengthen evidence that supports these recommendations,” the researchers said.

Therefore, all variable with a potential influence on outcomes should be considered to perform adjusted analysis in future studies (ie, risk factors of dementia in the general population as well as ADT type and duration), they added.

“Moreover, there are different types and different pathophysiologies of dementia, and the ADT effect on these different types of dementia should be assessed,” the researchers noted.