ADT Linked to Higher Alzheimer’s and Dementia Risk in Older Prostate Cancer Patients, Study Suggests

Men with prostate cancer who undergo treatment with androgen deprivation therapy (ADT) — a form of hormone therapy that aims to slow disease progression by reducing the levels of male hormones — may be more likely to develop Alzheimer’s disease and dementia, a large database study reports.

The study, “Association Between Androgen Deprivation Therapy Use and Diagnosis of Dementia in Men With Prostate Cancer,” was published in JAMA Network Open.

Androgen deprivation therapy has become a mainstay treatment for many prostate cancer patients, reducing the chances of cancer progression. But these approaches can have long-term adverse effects, including lower sexual function, reduced bone and cardiovascular health, as well as decreases in quality of life and functional status.

Cognitive decline is one of the major concerns associated with long-term exposure to ADT. There are many explanations for why they may be linked, including the fact that lower levels of male hormones can increase the chances of other conditions that are known risk factors for Alzheimer’s, such as diabetes, heart disease, depression, and loss of lean mass.

Nevertheless, the possible association between long-term exposure to ADT and the risk of Alzheimer’s and dementia is still uncertain.

Investigators at the University of Pennsylvania set out to explore the link between ADT exposure and Alzheimer’s and dementia risk among older men with prostate cancer.

The retrospective study involved a total of 154,089 men, 66 years or older, who had been diagnosed with localized or advanced prostate cancer between 1996 and 2003, and whose medical records had been stored at the National Cancer Institute’s Surveillance, Epidemiology, and End Results-Medicare linked database.

Among these people, 62,330 (mean age of 76) had started ADT within the first two years after being diagnosed, while the remaining 91,759 (mean age, 74) did not receive ADT. All were followed for an average of 8.3 years.

Results showed that men treated with ADT were more frequently diagnosed with Alzheimer’s (13.1% versus 9.4%) and dementia (21.6% versus 15.8%) compared to those who had never been exposed to ADT.

After adjusting for several factors, including disease characteristics and sociodemographic factors (e.g., age and marital status), investigators found that men treated with ADT were 14% more likely to develop Alzheimer’s and 20% more likely to develop dementia than those who had not been.

A risk of Alzheimer’s and dementia also tended to increase with a greater number of ADT doses:

• Men who had received between one and four doses of ADT were 19% more likely to develop Alzheimer’s and dementia;
• Men given five to eight doses of ADT were 28% more likely to develop Alzheimer’s and 24% more likely to develop dementia;
• Men treated with more than eight doses of ADT were 24% more likely to develop Alzheimer’s and 21% more likely to develop dementia.

“Our results suggest that clinicians need to raise their awareness about potential long-term cognitive effects of hormone therapy and discuss these risks with their patients,” Ravishankar Jayadevappa, PhD, a research associate professor of geriatrics, a senior fellow at the Leonard Davis Institute of Health Economics and the study’s principal investigator, said in a press release.

“Clinicians need to carefully weigh the long-term risks and benefits of exposure to ADT in patients with a prolonged life expectancy and stratify patients based on dementia risk prior to ADT initiation,” the scientists wrote.

But, “dementia may have a latency period of 1 decade or more prior to cognitive manifestations, with some cerebrospinal fluid, serum, and neuroimaging biomarkers present many
years before diagnosis. Hence, it is possible that ADT has a modifying or augmenting, rather than de novo, effect on development of dementia,” they concluded, recommending further study “to characterize individuals undergoing ADT who are at high risk of developing earlier dementia.”