Here we have a new meta-analysis of research on the neurocognitive risk associated with ADT. The study has not been published yet in the peer reviewed literature, but it is available online, and an abstract was published in the spring in the Journal of Urology.
The data was extracted from large retrospective data sets that identify correlations between ADT and select psychological problems for prostate cancer patients. The sample size is impressive; twenty-seven studies are pooled, which collective compare data from over 900,000 prostate cancer patients, who received ADT, with over 1.2 million patients, who did not receive ADT, as well as another 330,000+ patients with neither prostate cancer nor treatment with ADT.
If one only reads the Abstract, the conclusions seem scary. But there are some interesting points buried in the body of the paper not mentioned there.
Granted, the paper documents an increased risk of dementia and depression in prostate cancer patients on ADT, but that has been reported many times before. However, this study goes further and distinguishes Alzheimer’s disease from vascular dementia and also reports an increased risk of Parkinson's disease. Although that was only documented in three of the 27 studies included in the meta-analysis.
Before we dig into the details, one should understand that researchers can most easily find significance differences between populations when the sample sizes are very large, as they are here. Retrospective studies like this can only find correlations, which is not the same as identifying causal links. All the data in this study are presented as hazard ratios, where a significant hazard ratio of 1.66 indicates a likelihood of a 66% increase of the incidence of the condition at the population level. That, by the way, is the highest hazard ratio reported in this study and it’s for depression, which is the best studies neurocognitive disorder assessed with ADT. From other studies, we already know that depression is common with ADT, but not invariable and not demonstrable in the majority of men on ADT.
So, let's get into some of the new findings…
1.There is some hint that the specific form of androgen suppression (i.e., the “treatment modality”) may correlate with the risk of Alzheimer disease, but this warrants further research
2. Age appears to be a factor with no increased risk for men on ADT younger than 65 but greater risk for men over 65.
3. In comparable studies from around the world, “only cohorts from America showed an increased risk of dementia with ADT.” Since this increased risk was not seen in studies from Europe or Asian, the authors pointed out that “genetic and environmental factors may play a role in modifying the risk of cognitive decline in patients with prostate cancer”.
On this last point, dementia is progressive and not something that can be cured. However, lifestyle interventions—e.g., maintaining a heart healthy diet, controlling one’s weight, and getting a good amount of physical exercise—can all limit the risk of depression and cognitive impairment as we age regardless of whether we are starting on ADT or not.
Reference:
Hinojosa-Gonzalez, D., Zafar, A., Saffati, G., Kronstedt, S., Zlatev, D., & Khera, M. (2023). Androgen Deprivation Therapy for Prostate Cancer and Neurocognitive Disorders: A Systematic Review and Meta-Analysis. https://doi.org/10.21203/rs.3.rs-3221041/v1
Note: A preprint that has been posted on Research Square, but not yet published in a peer-reviewed journal.