Cognitive changes associated with ADT: a review of the literature

The use of androgen deprivation therapy (ADT) has increased since the early 1990s after early detection efforts and greater use of the prostate-specific antigen (PSA) test. Although ADT is associated with favorable clinical outcomes, ADT has been associated with an increased risk for cardiovascular disease, increased serum cholesterol, triglycerides, insulin resistance, body mass index and fat body mass. Here we review findings from 11 clinical studies examining the effects of ADT on cognition as measured by standardized tests in cognitive domains such as verbal and spatial memory. Most of these studies have important limitations, including small sample sizes, suboptimal control groups and baseline group differences in confounding factors. Despite these limitations, the best designed studies, those comparing patients on ADT to healthy controls, generally suggest that spatial memory might be especially sensitive to the effects of ADT. Critically, to date there is only one study involving random assignment of ADT versus close clinical observation. That study revealed a decrease in verbal memory with ADT, but was limited in sample size and did not include a measure of spatial memory. A recent observational study revealed no substantial evidence of cognitive impairment with ADT, even in the domain of verbal memory. Like the randomized study, however, this large observational study lacked a measure of spatial memory. Overall, the studies with the best controls suggest a potential negative impact of ADT on spatial memory, and perhaps verbal memory, and a need for continued investigation of the impact of ADT on cognition, particularly in these two cognitive domains.