Few papers about the side effects of androgen deprivation have received as much media coverage as the one published earlier this month in JAMA Network Open by Jayadevappa et al. (2019). The paper is titled “Association between Androgen Deprivation Therapy Use and Diagnosis of Dementia in Men with Prostate Cancer". The authors take a retrospective look at the risk of Alzheimer disease and dementia in general for 62,330 men who received ADT within two years of getting a prostate cancer diagnosis. To do so, the authors compared their medical histories to the medical histories of 91,759 prostate cancer patients who did not receive ADT. The mean follow-up time was 8.4 years.
The data show increased risk of cognitive impairment associated with ADT. Furthermore, that risk increased with the number of doses of ADT that the men received.
Those who follow this blog regularly may know that the cognitive impact of ADT has been a controversial topic. Indeed, we have reviewed several papers that have reported divergent results. But this new paper presents the strongest results so far and suggests a real increased risk for Alzheimer disease, specifically, and for dementia in general.
There are a variety of qualifying points to be made about this study, many of which are not covered within shorter popular news reports. So, for example, the majority of men on ADT did not get diagnosed with cognitive impairment during the study. For Alzheimer disease, ADT raised the risk from 9.4 to 13.1%, controlling for the age of the men. For dementia the rise was from 15.8 to 21.6%. That means that most patients on ADT are not likely to experience cognitive impairment due to this treatment, particularly if they're not on the treatment long-term.
Another thing to note about these data is that many of the men were started on ADT very quickly after they received their prostate cancer diagnosis. We may assume that they had not been monitoring their health perhaps as much as they could have and received their cancer diagnosis a bit late, when the disease was fairly advanced. Otherwise they would not have started so quickly on ADT. It is possible that these men had a disproportionately large number of additional risk factors for cognitive impairment, such as poor cardiovascular status and health overall.
The new JAMA Network Open paper does not explicitly discuss whether the ADT increases cognitive risk directly. ADT may influence other factors associated with increased risk of cognitive impairment, such as cardiovascular health overall. Furthermore, the report does not say anything about what one can do to limit the risk of cognitive side effects from LHRH drugs. Here is where preemptive education may be most important, for there is already evidence that maintaining one's cardiovascular fitness via diet and exercise can reduce the risk of cognitive impairment with age [See the Gheysen et al., 2019 article cited below]. This makes it particularly crucial that patients starting on ADT be advised about what they can do to limit the risks of cognitive impairment.
To read the full JAMA Network Open article, see:
Jayadevappa, R., Chhatre, S., Malkowicz, S.B., Parikh, R.B., Guzzo, T., & Wein, A.J. (2019). Association between androgen deprivation therapy use and diagnosis of dementia in men with prostate cancer. JAMA Network Open, 2(7), e196562. doi: 10.1001/jamanetworkopen.2019.6562
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2737101
To read the full article about physical activity and cognitive impairment, see:
Gheysen F, Poppe L, DeSmet A, Swinnen S, Cardon G, De Bourdeaudhuij I, Chastin S, & Fias W. (2018). Physical activity to improve cognition in older adults: can physical activity programs enriched with cognitive challenges enhance the effects? A systematic review and meta-analysis. International Journal of Behavioral Nutrition & Physical Activity, 15(1):63. doi: 10.1186/s12966-018-0697-x.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032764/