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From the Desk of the Associate Editor: Androgen deprivation therapy for prostate cancer and dementia risk: a systematic review and meta-analysis

Androgen deprivation therapy (ADT) causes a host of well-recognized side effects. Recent epidemiological and clinical evidence suggests that ADT may also be associated with dementia and cognitive impairment. Potential physiological explanations for these observations include altered neuron growth and axonal regeneration, increased ß-amyloid protein levels, and exacerbation of cardio-metabolic disease (including but not limited to cerebrovascular disease), all of which may occur in an androgen-deprived state.

These investigators undertook a systematic review and meta-analysis of existing literature of ADT and dementia in prostate cancer patients. They utilized standard meta-analytic techniques to identify and analyze nine studies incorporating over 50,000 patients. They ascertained three outcomes: any dementia, all-cause dementia, and Alzheimer’s disease. 

ADT was associated with a robust 47% increased risk of any dementia (hazard ratio (HR),1.47, 95% confidence interval (CI), 1.08-2.00, p=0.02) and 46% increased risk of all-cause dementia (HR,1.46, 95% CI, 1.05-2.02, p < 0.001). The risk of Alzheimer’s disease approached but did not attain significance (HR, 1.25, 95% CI, 0.99-1.57, p = 0.06).  

The take home point is that these findings are preliminary and should not yet inform clinical care. The absolute risk of incident dementia in the setting of ADT remains undefined and is likely quite small. Moreover, eight of the nine studies included in this meta-analysis were retrospective population-based analyses susceptible to bias by age, medical comorbidities, and other potential confounders. Thus, while associations of ADT with dementia and cognitive decline are compelling and merit additional research, these data should not drive treatment decisions. 

Written By: J. Kellogg Parsons, MD, MHS

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