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Adverse Effects of Androgen Deprivation Therapy on Cognitive Function and Dementia in Men with Prostate Cancer: A Systematic Review and Meta-Analysis
Alexander P. Cole, MD¹, Maxine Sun, PhD², Nawar Hanna, MD¹, Toni K. Chouiri, MD³, Quoc-Dien Trinh, MD¹.
¹Brigham & Women's Hospital- Division of Urological Surgery, Boston, MA, USA, ²Brigham & Women's Hospital- Center for Surgery and Public Health, Boston, MA, USA, ³Dana-Farber Cancer Institute, Lank Center for Genitourinary Oncology, Boston, MA, USA.

Background: Use of androgen deprivation therapy (ADT) for prostate cancer has many well-known side effects. ADT may confer a higher risk of cognitive impairment. Published results are variable and lack consensus. Our objective was to perform meta-analysis of the risk of overall cognitive impairment in men receiving ADT for prostate cancer. Methods: Relevant studies were identified through the search of English language articles indexed in PubMed, Medline, PsycINFO, Cochrane Library and Web of Knowledge/Science until December 21^st2016. Articles were included if they were published in English, reported on original research with adult male subjects undergoing treatment for prostate cancer, incorporated longitudinal comparisons, and included a control group. Controlled intervention studies were required to assess an established cognitive-related endpoint that was measured by a validated instrument, and measure cognitive impairment based on the International Cognition and Cancer Task Force (ICCTF) criteria. The effect of ADT on cognitive impairment was pooled using a random-effects model for controlled intervention and case-control studies separately. Results: Of 221 abstracts, 25 were selected for full-text review, and 8 studies, with 2 controlled studies and 6 case-control studies were identified. Overall cognitive impairment was not significantly different when the results of the 2 prospective studies were pooled (OR: 1.57, 95% CI: 0.50-4.92, P= 0.44), with significant heterogeneity between estimates (I²: 83%). In retrospective data, the odds of developing any cognitive impairment were significantly higher in men treated with ADT (HR: 1.37, 95% CI: 1.06-1.77, P= 0.02), with considerable heterogeneity (I²: 84%). Conclusions: The relationship between overall cognitive impairment and use of ADT defined according to the ICCTF criteria in a pooled-analysis of two prospective studies was inconclusive. Although retrospective studies suggest a higher risk of overall cognitive impairment after ADT, we caution readers not to over-interpret this finding given the limitations of retrospective data. Better well-designed prospective studies are needed to assess the effect of ADT on cognitive impairment with long-term follow-up.

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