Risk of Alzheimer’s Disease Among Senior Medicare Beneficiaries Treated With Androgen Deprivation Therapy for Prostate Cancer

Abstract

Purpose To assess the relative risk of Alzheimer's disease (AD) among patients with prostate cancer who received androgen deprivation therapy (ADT), after adjustment for other cancer therapies. Methods Data from demographics, survival, diagnoses codes, procedure codes, and other information about beneficiaries age 67 years or older in the Medicare claims database was assessed to determine the unadjusted and adjusted risks of AD and of dementia from ADT. The prespecified survival analysis method was competing risk regression. Results Of the 1.2 million fee-for-service Medicare beneficiaries who developed prostate cancer in 2001 to 2014, 35% received ADT. Of these, 109,815 (8.9%) and 223,765 (18.8%) developed AD and dementia, respectively, and 26% to 33% died without either outcome. Unadjusted rates of AD and all-cause mortality per 1,000 patient-years were higher among ADT recipients; the unadjusted rates of AD were 17.0 and 15.5 per 1,000 person-years in recipients and nonrecipients, respectively, and the unadjusted rates of all-cause mortality were 73.0 and 51.6 per 1,000 person-years, respectively. The unadjusted rates for dementia in ADT recipients versus nonrecipients were 38.5 and 32.9, respectively, and the unadjusted rates of mortality were 60.2 versus 40.4, respectively. However, after analysis was adjusted for other cancer therapies and other covariates, patients with ADT treatment had no increased risk of AD (subdistribution hazard ratio [SHR], 0.98; 95% CI, 0.97 to 0.99) and had only a miniscule (1%) risk of dementia (SHR, 1.01; 95% CI, 1.01 to 1.02); patients treated with ADT were more likely to die before progression to AD (SHR, 1.24; 95% CI, 1.23 to 1.24) or dementia (SHR, 1.26; 95% CI, 1.25 to 1.26). The risks of AD and dementia were not associated with duration of ADT (ie, no dose effect). Other secondary analyses confirmed these results. Conclusion These data suggest that ADT treatment has no hazard for AD and no meaningful hazard for dementia among men age 67 years or older who are enrolled in Medicare.

Hard Problems Need “Soft” Science: Integrating Quality of Life into Treatment Decision Making

“…Whether cognitive change occurs as a consequence of treatment for prostate cancer is debated [4][5][6][7]. The current study reported no difference in cognitive function after 12 wk of therapy between the two treatments.…”

An Updated Review: Androgens and Cognitive Impairment in Older Men

“…Patients over 70 years of age have the greatest risk for AD after ADT compared with patients under 70 years of age (43). However, due to heterogeneity of general characteristics and study methods, some studies have shown that ADT is not associated with dementia or AD (44)(45)(46)(47)(48). A recent meta-analysis with high evidence grade confirmed that ADT increased the risk for dementia in PCa patients (49), suggesting that low androgen derived from ADT is an important cause of cognitive dysfunction.…”

Type of Androgen Deprivation Therapy and Risk of Dementia Among Patients With Prostate Cancer in Taiwan

“…Observational studies on the association between ADT use and dementia risk have reported inconsistent results. 5 , 6 , 7 , 8 , 9 , 10 , 11 Two institution-based studies 7 , 8 reported that ADT use was associated with increased risk of developing AD or all-cause dementia, which has drawn public attention to this issue. However, possible detection bias, immortal time bias, and inadequate statistical power to analyze dementia risk by ADT type limited the interpretation of these previous findings.…”

“… 12 Subsequent studies did not confirm this positive association. 9 , 10 , 11 A large population-based study in the UK that used time-dependent exposure and robust methodology to reduce bias 9 reported no association of ADT with dementia or AD. 9 An analysis of 1.2 million Medicare beneficiaries with prostate cancer 10 reported a clinically irrelevant risk of all-cause dementia (subdistribution hazard ratio [HR], 1.01; 95% CI, 1.01-1.02).…”