LA JOLLA, CA—Research has been conflicting on whether androgen deprivation therapy is related to dementia.

A research letter in JAMA Oncology pointed out that two studies reported a strong statistically significant association between ADT and both dementia and Alzheimer’s disease in patients with prostate cancer, but both looked at heterogeneous populations, including patients with localized and metastatic disease, treated with curative and palliative intent, and ADT use in the upfront or recurrent setting.1

San Diego VA Health System-led researchers suggested confounding factors could have been present, such as chronic pain, salvage treatments or chemotherapy. The study team hypothesized that no statistically significant association would exist between ADT use and the development of dementia in men with PC who received definitive radiotherapy after controlling for multiple sources of selection bias.

Their cohort study included VA patients diagnosed with nonmetastatic PC from Jan. 1, 2001, to Oct. 31, 2015, who received definitive radiotherapy with or without ADT. Excluded were patients with a prior diagnosis of mild cognitive impairment, stroke and dementia or a diagnosis of dementia within one year of PC diagnosis, as well as those who underwent other treatment modalities, including radical prostatectomy, or who did not receive definitive treatment.

The study also excluded patients who initiated ADT more than a year after their PC diagnosis to avoid inclusion of patients with metastatic disease and those treated with chemotherapy, which sometimes is related to development of dementia.

Defined as the primary outcome was new development of any form of dementia. Secondary outcomes included vascular dementia and Alzheimer disease.

Ultimately, the cohort included 45,218 men followed up for a median of 6.8 years (interquartile range, 4.1-9.9 years). Of those, 1,497 patients were diagnosed with any dementia during study follow-up—335 with vascular dementia, 404 with Alzheimer’s disease, and 758 had other or unclassified dementia.

Results indicated no statistically significant association between ADT use and any dementia (SHR, 1.04; 95% CI, 0.94-1.16; P = .43), vascular dementia (SHR, 1.20; 95% CI, 0.97-1.50; P = .10), or Alzheimer’s disease (SHR, 1.11; 95% CI, 0.91-1.36; P = .29) (Table). Furthermore, no association was found between ADT length of one year or less with any dementia (SHR, 1.01; 95% CI, 0.89-1.15; P= .89) and ADT length greater than a year with any dementia (SHR, 1.08; 95% CI, 0.95-1.24;P= .21) (Table).

Researchers said a sensitivity analysis using time-varying ADT exposure revealed no significant association between ADT and any dementia (SHR, 1.04; 95% CI, 0.94-1.16; P= .43), vascular dementia (SHR, 1.21; 95% CI, 0.97-1.50; P= .09), and Alzheimer’s disease (SHR, 1.11; 95% CI, 0.91-1.35; P= .29).

“These results may mitigate concerns regarding the long-term risks of ADT on cognitive health in the treatment of PC,” study authors concluded.

1 Deka R, Simpson DR, Bryant AK, et al. Association of Androgen Deprivation Therapy With Dementia in Men With Prostate Cancer Who Receive Definitive Radiation Therapy. JAMA Oncol. 2018;4(11):1616–1617. doi:10.1001/jamaoncol.2018.4423