Philadelphia—Older men using androgen deprivation therapy to treat prostate cancer are at higher risk for subsequent diagnosis of Alzheimer’s disease or other dementia, according to a new study.

The report in JAMA Network Open says that conclusion is based on data for 154,089 older men diagnosed with prostate cancer. University of Pennsylvania–led researchers compared 62,330 patients with an average age of 76 years, who received the hormone-suppressing therapy, with 91,759 men, average age 74 years, who didn’t have that treatment. Participants were followed for an average of 8 years.

The study points out that the possible association between ADT exposure and cognitive dysfunction represents a growing concern. The authors list several possible mechanisms behind the association, including that decreasing androgen levels could increase risk factors for Alzheimer’s disease and dementia, including loss of lean body mass, diabetes, cardiovascular disease, and depression. In addition, they write, a causative relationship could exist between lower testosterone levels and impaired cognitive function, possibly related to impaired neuron growth and axonal regeneration or accumulation of abnormally folded beta-amyloid protein.

Researchers describe how previous studies using national samples have reported conflicting results regarding the diagnosis of Alzheimer’s disease or dementia among older patients with prostate cancer exposed to ADT. Based on their results, they conclude, “Clinicians must carefully weigh the long-term risks and benefits of exposure to androgen deprivation therapy in patients with a prolonged life expectancy and stratify patients by dementia risk prior to androgen deprivation therapy initiation.”

The retrospective cohort study used data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results–Medicare linked database. Participants were newly diagnosed with prostate cancer between 1996 and 2003, with analyses conducted between November 1, 2018, and December 31, 2018.

Results indicate that exposure to ADT, compared with no ADT exposure, was associated with a diagnosis of Alzheimer’s disease (13.1% vs. 9.4%; difference, 3.7%; 95% CI, 3.3%-3.9%; P <.001; hazard ratio [HR], 1.14; 95% CI, 1.10-1.18) and dementia (21.6% vs. 15.8%; difference, 5.8%; 95% CI, 5.4%-6.2%; P <.001; HR, 1.20; 95% CI, 1.17-1.24).

The study team notes that for one to four doses of ADT, the HR was 1.19 (95% CI, 1.15-1.24) for Alzheimer’s disease and 1.19 (95% CI, 1.15-1.23) for dementia. For five to eight ADT doses, the HR rose to 1.28 (95% CI, 1.22-1.35) for Alzheimer’s disease and 1.24 (95% CI, 1.19-1.29) for dementia.

For more than eight doses of ADT, the HR was 1.24 (95% CI, 1.16-1.34) for Alzheimer’s disease and 1.21 (95% CI, 1.15-1.28) for dementia, according to the researchers, who calculated that the number needed to harm was 18 patients (95% CI, 17-19 patients) and 10 patients (95% CI, 9.5-11 patients) for Alzheimer’s disease and dementia, respectively.

“Among elderly patients with prostate cancer, ADT exposure was associated with subsequent diagnosis of Alzheimer disease or dementia over a follow-up period of at least 10 years,” the study concludes.

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