ADT use associated with Alzheimer’s disease, dementia
medwireNews: Older prostate cancer patients who use androgen deprivation therapy (ADT) may be at increased risk for developing Alzheimer’s disease or dementia, findings indicate.
“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,” write Ravishankar Jayadevappa and co-investigators, from the University of Pennsylvania in Philadelphia, USA, in JAMA Network Open.
Our study contributes to existing knowledge while adding some unique elements to the literature.
In a comment to the press, David Montgomery, director of research at the charity Prostate Cancer UK, cautioned however that “[h]ormone therapy is a highly effective treatment for prostate cancer and can keep the disease at bay for many years. While we know it can be associated with a number of side effects, we would not encourage men to change their treatment as a result of this study alone.”
Among 154,089 SEER–Medicare participants aged at least 66 years who were newly diagnosed with localized or advanced prostate cancer between 1996 and 2003, Alzheimer’s disease occurred over an average follow-up of 8.3 years in 13.1% of the 62,330 patients who received ADT within 2 years of diagnosis and in 9.4% of the 91,759 men who did not use ADT.
The between-group difference was significant and equated to a propensity score-adjusted hazard ratio (HR) of 1.14 for ADT users versus nonusers.
The incidence of dementia was similarly higher in the ADT than non-ADT group, at 21.6% and 15.8%, respectively, and a propensity score-adjusted HR of 1.20.
The risk for Alzheimer’s disease was higher for men who received more than 8 or 5–8 doses compared with those given 1–4 doses of ADT, with HRs relative to no use of 1.24, 1.28, and 1.19, respectively. The findings were similar for dementia, with corresponding HRs of 1.21, 1.24, and 1.19.
The number needed to harm for Alzheimer’s disease was 18, while it was 10 for dementia.
medwireNews previously reported on research showing a difference in risk for non-Alzheimer’s dementia by type of ADT, but the present study did not include such a subgroup analysis.
We must wait for the results from more observational studies before finding an answer to this question.
The current investigators did, however, conduct sensitivity analyses by comorbidity, treatment combination, and cancer stage, which revealed some differences across certain subgroups.
For instance, the association between ADT use and risk for Alzheimer’s disease or dementia only held true for the subgroup with no rather than 1–2 or more than two comorbidities. And in the subgroup of men who underwent surgery, ADT use was linked to a significantly reduced risk for Alzheimer’s disease (HR=0.92) but not dementia (HR=1.16), whereas chemotherapy-treated patients had no increased risk for either condition.
Jayadevappa and colleagues comment that although their data indicates “an association between ADT and subsequent dementia diagnosis, we were unable to further investigate possible biological mechanisms of this association.”
They continue: “It is crucial to establish whether this association is mediated by long-term androgen suppression, especially as dual androgen blockade with second-generation antiandrogens moves earlier in the treatment course of prostate cancer.”
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