Androgen Deprivation Therapy and the Risk of Dementia in Patients With Prostate Cancer

Abstract

Purpose Recent observational studies have associated the use of androgen deprivation therapy (ADT) with an increased risk of dementia and Alzheimer's disease, but these studies had limitations. The objective of this study was to determine whether the use of ADT is associated with an increased risk of dementia, including Alzheimer's disease, in patients with prostate cancer. Patients and Methods Using the United Kingdom's Clinical Practice Research Datalink, we assembled a cohort of 30,903 men newly diagnosed with nonmetastatic prostate cancer between April 1, 1988 and April 30, 2015, and observed them until April 30, 2016. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios with 95% CIs of dementia associated with the use of ADT compared with nonuse. ADT exposure was lagged by 1 year to account for delays associated with the diagnosis of dementia and to minimize reverse causality. Secondary analyses assessed whether the risk varied with cumulative duration of use and by ADT type. Results During a mean (standard deviation) follow-up of 4.3 (3.6) years, 799 patients were newly diagnosed with dementia (incidence, 6.0; 95% CI, 5.6 to 6.4) per 1,000 person-years. Compared with nonuse, ADT use was not associated with an increased risk of dementia (incidence, 7.4 v 4.4 per 1,000 person-years, respectively; adjusted hazard ratio, 1.02; 95% CI, 0.87 to 1.19). In secondary analyses, cumulative duration of use ( P for heterogeneity = .78) and no single type of ADT were associated with an increased risk of dementia. Conclusion In this population-based study, the use of ADT was not associated with an increased risk of dementia. Additional studies in different settings are needed to confirm these findings.

Androgen‐deprivation therapy, dementia, and cognitive dysfunction in men with prostate cancer: How much smoke and how much fire?

“…Within the last 2 years there have been a number of large observational studies reporting incident dementia in patients who receive ADT for prostate cancer (Table ) . Propelling the public concerns about an association between ADT use and dementia was a recent single‐institution, retrospective study undertaken at Stanford University .…”

“…The follow‐up period began on the date of the PC diagnosis plus the exposed group's median time from diagnosis to ADT receipt. The latter is an important definition, because it may have introduced immortal time bias, in that some ADT recipients may have started ADT years after their PC diagnosis, giving the nonusers a longer average follow‐up, which inflates the denominator of the rate and overestimates the hazard ratio (HR) …”

“…49 CLINICAL DATA: USE OF ADT AND THE RISK OF DEMENTIA Within the last 2 years there have been a number of large observational studies reporting incident dementia in patients who receive ADT for prostate cancer ( Table 2). [50][51][52][53] Propelling the public concerns about an association between ADT use and dementia was a recent single-institution, retrospective study undertaken at Stanford University. 50 Information collected through a previously validated text-processing method was gathered on patients between 1994 and 2013 to include exposed (received ADT) and nonexposed patients with PC.…”

“…The latter is an important definition, because it may have introduced immortal time bias, in that some ADT recipients may have started ADT years after their PC diagnosis, giving the nonusers a longer average follow-up, which inflates the denominator of the rate and overestimates the hazard ratio (HR). 53 Of the 9272 patients who met inclusion criteria, 1826 (19.7%) received ADT. In total, 314 incident cases of dementia were diagnosed during a median follow-up of 3.4 years.…”

“…Kao et al tracked patients for an In a recently published, large, retrospective, UK population-based study, the use of ADT was not associated with an increased risk of dementia ( Table 2). 53 By using the world's largest primary care database (700 practices), the Clinical Practice Research Datalink retrieved incident diagnoses of dementia by read code classification among 30,903 eligible patients. Each patient's dementia subtype was recorded by the general practitioner, a method that has demonstrated high validity.…”