An article just published on line in the journal Urologic Oncology looks at the vexing problem of the degree to which extended periods on androgen deprivation therapy (ADT) may have significant impact on the day-to-day cognitive functioning of at least a proportion of men with progressive forms of prostate cancer.
We should be very clear, up front, that this paper by Wu et al. is really an attempt to: (1) review the relatively small amount of published data available to date; (2) re-assess the clinical problem based on detailed patient experiences; (3) note the ways in which interventions may be possible to maintain or improve cognitive function in those at risk; and (4) outline a potential research pathway to gain better understanding of the impact of ADT on cognitive function. It does not offer any good, new data on either the size of the problem or ways in which to prevent or treat these side effects of long-term ADT.
Wu et al. note early in their paper that the degree to which ADT actually affects cognitive function in any individual is complicated by the inherent effects of aging on cognitive function. Decreased levels of serum testosterone (T) are an inevitable consequence of ADT for men with prostate cancer … but reductions in levels of serum T are also a consequence of aging and are associated with increased risk for Alzheimer’s disease too.
The authors then go on to summarize the relatively small number of studies conducted to date into cognitive functioning of prostate cancer patients being treated with ADT. They note that most of these studies have involved small numbers of men (fewer than 100 ADT patients in even the largest study conducted to date) followed for 2 years or less. However, many men may actually be on continuous ADT for 5, 10, or even 20 years today.
Wu et al. then conducted a small pilot study in just 11 self-referred volunteers to try to get greater clarity on whether and how the patients felt that ADT had affected their cognitive functioning over time. Clearly this was not a random sample of men being treated with ADT, so the learnings need to be assessed with caution!
According to Wu and her colleagues:
- 8/11 patients reported impairments in multiple cognitive domains.
- Among lower level cognitive functions
- 5/11 patients reported problems with concentration.
- 5/11 patients reported problems with information processing.
- 6/11 patients reported problems with visual/verbal memory.
- 3/11 patients reported problems with visual information processing and/or visual-spatial function.
- 1/11 patients reported problems with verbal fluency.
- 2/11 patients reported problems with high level “executive” functioning (e.g., decision making).
- 5/11 patients reported signs and symptoms of neurological dysfunction.
- 3/11 patients reported “neuro-fatigue” (brain tiredness)
- 3/11 patients reported “adynamia” (apathy, disinterest)
- All men reporting cognitive impairments also reported
- Functional problems at work
- The need to cut down on time at work or change jobs or stop work altogether
- 1/11 patients attributed his cognitive function problems entirely to the aging process, discounting any effects of ADT.
- 4/11 patients reported that either their spouse or others had noticed changes in their cognitive functioning.
The symptoms and syndromes identified by Wu and her colleagues are ones that The “New” Prostate Cancer InfoLink has come across time and again over the past 20 years of monitoring and assisting men with prostate cancer and their caregivers. It is true that they only appear to affect a subset of patients, but it also appears to be a relatively large subset (perhaps 25 to 30 percent of all men on long-term ADT?), and for some younger, employed men (in particular) the consequences can be extremely problematic. One of the terms not specifically mentioned by Wu et al., but which we have come across commonly, is the loss of the ability to “multi-task” and the need to really focus on just doing one thing at a time.
Wu et al. go on to note that while there are no published data on the application of cognitive rehabilitation techniques to prostate cancer patients on ADT, there are some (small) studies on cognitive rehabilitation among other categories of cancer patients. The authors also note the roles of physical exercise and estradiol therapy in maintenance of cognitive function, but again the data are limited.
The “New” Prostate Cancer InfoLink sees this paper as an interesting attempt to redefine the need for structured research into the effects and management of cognitive dysfunction among prostate cancer patients treated with ADT. As the authors note, increasing life expectancies may lead to an increase in the numbers of men being managed with long-term ADT over the next 20 to 30 years, in which case the prevalence of cognitive dysfunction may significantly increase, and the need to be able to avoid, prevent, or treat such dysfunction will increase right along with it.
The “New” Prostate Cancer InfoLink thanks Dr. Lisa Wu for providing a copy of the full text of this article on which this summary is based.