Androgen-deprivation therapy (ADT) is associated with an increased risk for the future development of Alzheimer's disease in men with prostate cancer, according to a retrospective study of nearly 17,000 patients.
There were 125 new diagnoses of Alzheimer's disease in the study cohort during a median follow-up of 2.7 years.
But the incidence of Alzheimer's was nearly twice as high in the 2397 men who had received ADT as in the 14,491 who had not (hazard ratio [HR], 1.88; 95% confidence interval [CI], 1.10 - 3.20; P = .02).
And for men who had taken ADT for longer than 12 months, the incidence was even higher (HR, 2.12; 95% CI, 1.11 - 4.03; P = .01). In fact, the risk for Alzheimer's disease was significantly higher in men treated with ADT for more than 12 months than in those treated for less than 12 months (P for trend = .016).
These findings support "an association between the use of ADT in the treatment of prostate cancer and an increased risk of Alzheimer's disease," but prospective studies are needed for confirmation, conclude the authors, led by Kevin Nead, MD, a radiation oncologist at the University of Pennsylvania in Philadelphia.
The study was published online today in the Journal of Clinical Oncology.
Men who received chemotherapy were excluded from the analysis, given the evidence for "chemotherapy-associated cognitive dysfunction," the authors explain.
"There are a growing number of studies suggesting that the use of ADT may be associated with cognitive changes," Dr Nead told Medscape Medical News, adding that "some of these changes overlap with characteristic features of Alzheimer's disease."
Dr Nead and his colleagues note that a number of "plausible mechanisms" might explain a "neuropathic effect of androgen deficiency in the etiology of Alzheimer's disease," including the fact that androgens have been shown to aid in neuron growth and axonal regeneration.
Furthermore, they point out, in men with Alzheimer's disease, testosterone supplementation has been shown to improve spatial and verbal memory.
However, this is the first study to specifically examine the association between ADT treatment for prostate cancer and future risk for Alzheimer's disease, they point out.
Should Patients Be Cautioned?
Dr Nead, who was at Stanford University in California when the study began, does not endorse discussing with patients the possible tie between ADT use and the development of Alzheimer's disease — at least, not yet.
"Counselling patients regarding the risks of Alzheimer's disease associated with ADT may be appropriate if future studies confirm these findings," Dr Nead said.
But another researcher believes that the subject of cognitive decline should be discussed.
"Urologists should discuss the risk of worse cognitive function with prostate cancer patients when discussing the risks and benefits of ADT, a potentially life-saving treatment," said Brian Gonzalez, PhD, from the Rutgers Cancer Institute of New Jersey in New Brunswick.
Dr Gonzalez was lead author of a recent small prospective study, which showed that men with prostate cancer treated with ADT are more likely to experience cognitive impairment than men with prostate cancer treated with surgery and than men without prostate cancer, as reported by Medscape Medical News.
For practical reasons, Dr Nead's team focused on Alzheimer's and not more general cognitive problems, said senior author Nigam Shah, MBBS, PhD, a biomedical informatics researcher at the Stanford Center for Biomedical Informatics Research
Alzheimer's disease is "easier to identify in medical records," Dr Shah said in a press statement.
Dr Gonzalez said he is impressed with the data collection in the study. "The authors used sophisticated software to first identify patients treated with prostate cancer and then identify those treated with ADT and those who were later diagnosed with Alzheimer's," he explained.
In fact, the authors used proprietary data-mining technology to scan more than 5 million medical records from health systems at Stanford University (1994 to 2013) and Mount Sinai Hospital in New York City (2000 to 2013) to find the relevant cases.
In finding a near doubled risk for Alzheimer's disease associated with ADT, Dr Nead's team employed a propensity score-matched Cox regression analysis. They also report using a "traditional" multivariable-adjusted Cox regression analysis, which showed a statistically significant positive association, albeit a bit less dramatic (HR, 1.66; 95% CI, 1.05 - 2.64; P = .031).
The study was supported by the National Institutes of Health, the National Library of Medicine, and the National Institute of General Medical Sciences. Dr Shah is an inventor on patents owned by Stanford University that enable the use of clinical text for data-mining.
J Clin Oncol. 2015. Published online December 7, 2015. Abstract