Kevin T Nead1, Greg Gaskin2, Cariad Chester3, Samuel Swisher-McClure4, Nicholas J Leeper5, Nigam H Shah2. 1. Stanford Center for Biomedical Informatics Research, Stanford University School of Medicine, Stanford, California2Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia. 2. Stanford Center for Biomedical Informatics Research, Stanford University School of Medicine, Stanford, California. 3. Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, California. 4. Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia. 5. Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.
Abstract
IMPORTANCE: A growing body of evidence supports a link between androgen deprivation therapy (ADT) and cognitive dysfunction, including Alzheimer disease. However, it is currently unknown whether ADT may contribute to the risk of dementia more broadly. OBJECTIVE: To use an informatics approach to examine the association of ADT as a treatment for prostate cancer with the subsequent development of dementia (eg, senile dementia, vascular dementia, frontotemporal dementia, and Alzheimer dementia). DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, a text-processing method was used to analyze electronic medical record data from an academic medical center from 1994 to 2013, with a median follow-up of 3.4 years (interquartile range, 1.0-7.2 years). We identified 9455 individuals with prostate cancer who were 18 years or older at diagnosis with data recorded in the electronic health record and follow-up after diagnosis. We excluded 183 patients with a previous diagnosis of dementia. Our final cohort comprised 9272 individuals with prostate cancer, including 1826 men (19.7%) who received ADT. MAIN OUTCOMES AND MEASURES: We tested the effect of ADT on the risk of dementia using propensity score-matched Cox proportional hazards regression models and Kaplan-Meier survival analysis. RESULTS: Among 9272 men with prostate cancer (mean [SD] age, 66.9 [10.9] years; 5450 [58.8%] white), there was a statistically significant association between use of ADT and risk of dementia (hazard ratio, 2.17; 95% CI, 1.58-2.99; P < .001). In sensitivity analyses, results were similar when excluding patients with Alzheimer disease (hazard ratio, 2.32; 95% CI, 1.73-3.12; P < .001). The absolute increased risk of developing dementia among those who received ADT was 4.4% at 5 years (7.9% among those who received ADT vs 3.5% in those who did not receive ADT). Analyses stratified by duration of ADT found that individuals with at least 12 months of ADT use had the greatest absolute increased risk of dementia (hazard ratio, 2.36; 95% CI, 1.64-3.38; P < .001). Kaplan-Meier analysis demonstrated that ADT users 70 years or older had the lowest cumulative probability of remaining dementia free (log-rank P < .001). CONCLUSIONS AND RELEVANCE: Androgen deprivation therapy in the treatment of prostate cancer may be associated with an increased risk of dementia. This finding should be further evaluated in prospective studies.
IMPORTANCE: A growing body of evidence supports a link between androgen deprivation therapy (ADT) and cognitive dysfunction, including Alzheimer disease. However, it is currently unknown whether ADT may contribute to the risk of dementia more broadly. OBJECTIVE: To use an informatics approach to examine the association of ADT as a treatment for prostate cancer with the subsequent development of dementia (eg, senile dementia, vascular dementia, frontotemporal dementia, and Alzheimer dementia). DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, a text-processing method was used to analyze electronic medical record data from an academic medical center from 1994 to 2013, with a median follow-up of 3.4 years (interquartile range, 1.0-7.2 years). We identified 9455 individuals with prostate cancer who were 18 years or older at diagnosis with data recorded in the electronic health record and follow-up after diagnosis. We excluded 183 patients with a previous diagnosis of dementia. Our final cohort comprised 9272 individuals with prostate cancer, including 1826 men (19.7%) who received ADT. MAIN OUTCOMES AND MEASURES: We tested the effect of ADT on the risk of dementia using propensity score-matched Cox proportional hazards regression models and Kaplan-Meier survival analysis. RESULTS: Among 9272 men with prostate cancer (mean [SD] age, 66.9 [10.9] years; 5450 [58.8%] white), there was a statistically significant association between use of ADT and risk of dementia (hazard ratio, 2.17; 95% CI, 1.58-2.99; P < .001). In sensitivity analyses, results were similar when excluding patients with Alzheimer disease (hazard ratio, 2.32; 95% CI, 1.73-3.12; P < .001). The absolute increased risk of developing dementia among those who received ADT was 4.4% at 5 years (7.9% among those who received ADT vs 3.5% in those who did not receive ADT). Analyses stratified by duration of ADT found that individuals with at least 12 months of ADT use had the greatest absolute increased risk of dementia (hazard ratio, 2.36; 95% CI, 1.64-3.38; P < .001). Kaplan-Meier analysis demonstrated that ADT users 70 years or older had the lowest cumulative probability of remaining dementia free (log-rank P < .001). CONCLUSIONS AND RELEVANCE: Androgen deprivation therapy in the treatment of prostate cancer may be associated with an increased risk of dementia. This finding should be further evaluated in prospective studies.
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