A large-scale analysis of medical records revealed that men undergoing androgen deprivation therapy for prostate cancer treatment may be at almost twice the risk of eventually developing Alzheimer’s disease, and that the increased likelihood of the disease is proportional to ADT duration. The research paper, entitled “Androgen Deprivation Therapy and Future Alzheimer’s Disease Risk,” was published in the Journal of Clinical Oncology.
Previous research has suggested that low levels of testosterone, a direct consequence of androgen deprivation therapy (ADT), may leave the brain more vulnerable to the pathogenic neurodegeneration that leads to Alzheimer’s disease. Likewise, men with Alzheimer’s disease have been found to present lower testosterone levels when compared to healthy counterparts. This effect, not yet fully understood, has been linked to testosterone’s perceived protective effect on brain cells and to evidence suggesting that the production of amyloid beta, a protein involved in Alzheimer’s pathogenesis, increases as testosterone levels diminish.
To further investigate the benefits and risks of ADT and, for the first time, its possible association with Alzheimer’s risk, researchers initiated a retrospective study of electronic medical data of patients from hospitals at Stanford University and Mt. Sinai, New York, covering about 5 million individuals, of which 16,888 had been diagnosed with prostate cancer and met all inclusion and exclusion criteria. Among this group, 2,397 patients had received ADT. Using different statistical analyses and comparing the ADT-treated group with a similar group of patients who had not undergone ADT, the researchers showed that the ADT-treated patients went on to have significantly more Alzheimer’s diagnoses than the control group in the years following initiation of therapy.
According to one statistical calculation, the ADT patients were 88% more likely to be diagnosed with Alzheimer’s. Furthermore, researchers found that the risk correlated with the duration of treatment, meaning that the longer patients underwent ADT therapy the higher was their risk of Alzheimer’s. Such findings remained valid, even when researchers looked at each hospital’s data separately.
The researchers emphasized that their findings do not prove that ADT increases the risk of Alzheimer’s disease but clearly point to that possibility.
Lead author Kevin T. Nead, MD, MPhil, resident in the department of Radiation Oncology at the Perelman School of Medicine at the University of Pennsylvania, said in a press release: “Based on the results of our study, an increased risk of Alzheimer’s disease is a potential adverse effect of ADT, but further research is needed before considering changes to clinical practice. It’s hard to determine the precise amount of increased risk in just one study and important to note that this study does not prove causation. But considering the already-high prevalence of Alzheimer’s disease in older men, any increased risk would have significant public health implications.”