When it comes to the quality of life of patients on ADT one major area of research is the impact of ADT on cognition. Patients usually discuss this in terms of brain fog, problems with memory, or just problems in finding common things around their home. Despite a huge number of studies on the topic, there's not been a solid consensus about how ADT, either alone or combined with ARTAs, impacts patients’ cognitive abilities.
We now have a new comprehensive review and meta-analysis of the research that is more rigorous than any so far. Twenty studies are included in the systematic review built upon data from 1440 patients. Fifteen of those 20 had enough data to be used in a meta-analysis.
In the ADT book, we reference a 2014 meta-analysis, which was the most comprehensive meta-analysis previous analysis. That paper concluded that the best evidence for cognitive impairment was in the visuo-spatial domain. However, this new analysis questions that conclusion. The authors are careful to distinguish different types of trials, such as whether patients were compared to their baseline data only or whether there was a control group.
What the authors found in their new meta-analysis is that consistent evidence for objective cognitive impairment from ADT is still lacking. The authors offer some suggestions for why they got this result. For example, they noted that some 20 to 50% prostate cancer patients show some sign of objective cognitive decline even before they are exposed to ADT. This could be due to depression or anxiety directly or indirectly related to the stress of having advancing cancer.
The authors even found some evidence of cognitive improvement (!) when they compared patients tested at baseline and re-tested at a later date. They suggested that this could be the result of the participants learning how to take the tests from their previous exposure to the tests.
What is probably the most surprising and relevant take-away for patients from this paper is that authors found evidence of subjective cognitive decline with ADT. Objective cognition is measured with standardized tests whereas subjective cognition is documented by simply asking the patients various questions about whether they feel like they are having a harder time thinking, remembering, and finding things, whether they are words or objects in the world they live in.
From a patient's perspective what matters most is subjective sense of cognitive decline versus the objectivemeasures. It is that subjective impression of cognitive impairment that would be associated with distress in patients. It could be tied to fatigue, insomnia, and depression, which are common in cancer patients. One study that the authors cite, for example, shows that patients reporting subjective cognitive impairment showed insomnia as a mediating factor.
In the real-world objective cognitive impairment is worth assessing and finding ways to limit it for the safety of the patient. At the same time in the real world, it is subjective sense of brain fog and cognitive impairment that stresses out patients. If stressed out patients have poor sleep quality, that can lead to fatigue and depression. Patients in that situation may report a high level of brain fog which in turn can lead to problems with sleeping in a feedback loop fashion.
This may seem scary, but there is a somewhat positive side to the story. There are interventions that can help with sleep quality and depression, and perhaps help with the subjective sense of cognitive impairment. This can include various medications, but exercise alone has been shown to help with managing insomnia, daytime fatigue, and depression.
In contrast, it is harder to treat objective cognitive decline of the sort associated with aging.
This paper is superb not only in its thoroughness, but in pointing out that clinicians treating patients with ADT need to take seriously the patients’ concerns about brain fog and cognitive impairment…even if they’re not documented in standardized tests.
Reference:
Boué A, Joly F, Lequesne J, Lange M. Does hormone therapy impact cognition in patients with prostate cancer? A systematic review and meta-analysis. Cancer. 2024 Feb 2. doi: 10.1002/cncr.35210.