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Androgen Deprivation for Prostate Cancer Linked to Dementia

Prostate cancer.

Androgen deprivation therapy (ADT) is associated with diagnoses of dementia in men with prostate cancer, according to a new study

Androgen deprivation therapy, either alone or in combination with other forms of therapy, is an effective treatment for high-risk prostate cancer in all stages from localized to metastatic disease. However, it has its drawbacks, including potential long-term effects on bone, sexual, and cardiovascular health. According to researchers from the Perelman School of Medicine at the University of Pennsylvania, dementia needs to be added to that list of risks.

"The possible association between ADT exposure and cognitive dysfunction represents a growing concern. There are several purported mechanisms behind this association," write the researchers in their study, which has now been published in JAMA Network Open. The authors note that diminished levels of androgen may heighten risk factors for Alzheimer's disease and dementia, including loss of lean body mass, diabetes, cardiovascular disease, and depression. In addition, they note, lower testosterone may be causing impairments in cognitive functioning through avenues such as impaired neuron growth and axonal regeneration or through accumulation of abnormally folded β-amyloid protein, which has been found in the brains of Alzheimer's patients.

"Clarifying the association between ADT and dementia could improve shared decision making around the risks and benefits of ADT in prostate cancer," continue the researchers, led by first author Ravishankar Jayadevappa, PhD, Research Associate Professor of Geriatrics at the Perelman School and Senior Fellow at the University of Pennsylvania's Leonard Davis Institute of Health Economics.

The retrospective cohort study analyzed data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Medicare-linked database on 154,089 elderly men with prostate cancer, newly diagnosed between 1996 and 2003 and followed for a mean of 8.3 years. The researchers found that men who were administered ADT had a higher rate of Alzheimer's diagnosis than did those not given ADT (13.1% vs 9.4%), as well as higher rates of dementia (21.6% vs 15.8%).

The risks were higher with additional exposure to ADT. One to 4 doses of ADT produced a hazard ratio of 1.19 for both Alzheimer's disease and dementia, compared with hazard ratios of 1.28 for Alzheimer's disease and 1.24 for dementia in those receiving 5 to 8 doses of ADT. For patients receiving more than 8 doses of ADT, the hazard ratios were 1.24 and 1.21, respectively, for Alzheimer's disease and dementia.

"Our population-based study… shows that exposure to ADT was associated with increased hazard of both Alzheimer disease and dementia among elderly fee-for-service Medicare beneficiaries with prostate cancer," conclude the study authors. "The list of effective ADT agents has recently grown with the addition of androgen synthesis inhibitors and second-generation antiandrogens. Furthermore, data are accumulating for the use of such agents earlier in the course of disease progression. Our results suggest that 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."

For More Information

Jayadevappa R, Chhatre S, Malkowicz SB, et al (2019). Association between androgen deprivation therapy use and diagnosis of dementia in men with prostate cancer. JAMA Netw Open, 2(7):e196562. DOI:10.1001/jamanetworkopen.2019.6562

Image credit: Otis Brawley. Courtesy of the National Cancer Institute

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