Does long-term ADT really affect cognitive function or not?

After > 50 years of use of various forms of androgen deprivation therapy (ADT), we still don’t really have a clear idea of whether or the degree to which long-term, continuous ADT can affect cognitive function — although there is no doubt at all that many patients believe it does.

A new study  from a respected prostate cancer clinical research group at the University of Toronto (Alibhai et al.) has now reported data on the impact of continuous ADT on cognitive function over a period of 3 years in a total of 241 patients. In order to evaluate cognitive function over time, they used a total of 14 neuropsychological tests, which examined eight different cognitive “domains”; the tests were all administered five times over a period of 36 months.

Three different sets of patients were evaluated, broken down into the following groups, as follows:

  • Group A comprised 77 men with non-metastatic prostate cancer who were starting on continuous ADT (but the type of ADT being used is not specified in the abstract of the paper)
  • Group B comprised 82 men with prostate cancer who were not receiving ADT (prostate cancer controls)
  • Group C comprised 82 healthy men who did not have prostate cancer (healthy controls)

All the patients were ≥ 50 years of age and were matched based on their age and education. However, the patients were not “randomized” in any way to a particular management arm of the trial.

So here are the basic study findings:

  • The average (mean) age of the participants was 68.9 years.
  • The average (median) length of education  of the patients was 16 years.
  • The percentage of participants whose cognitive function declined by ≥ 1.5 standard deviations in ≥ 2 tests or by ≥ 2 standard deviations in ≥ 1 test(s) was similar across the three groups.
  • A global summary of cognitive change found no statistically significant worsening of cognitive function among men in Group A compared to men in Groups B and C.
  • Sensitivity analyses adjusting for duration of ADT and other factors did not materially alter the study findings.

The authors conclude that:

The ongoing use of ADT for up to 36 months does not appear to be associated with cognitive decline.

Since we haven’t seen the full text of this paper, we are hesitant to agree that this conclusion is strictly accurate (i.e., that there was really no decline at all in the cognitive function of any of the study participants on continuous ADT in Group A — or in the study participants in Groups B and C). It is possible that the more accurate conclusion might have been that:

The ongoing use of ADT for up to 36 months does not appear to be associated with a different degree of cognitive decline than that shown in comparable groups of prostate cancer control and health control patients.

Either way around, what the authors certainly appear to have found in this study is that continuous ADT did not adversely affect cognitive function any more than other normal factors in men ≥ 50 years of age with or without prostate cancer.

It seems likely to The “New” Prostate Cancer InfoLink that many patients who believe that ADT has affected their cognitive function will wonder about whether the form and methodology of this trial is sufficient to have actually demonstrated the result reported. Your sitemaster doesn’t feel able to comment on that. It certainly appears that the authors have made a sincere attempt to measure cognitive function over a period of 3 years in  an assiduous fashion. On the other hand, if significant effects on cognitive function only occur in (say) 15 percent of men on continuous ADT, then only 15 percent of the 77 men in this study (i.e., 12 men) might have shown such effects, and so one is then faced with the question of whether the sample size was large enough to measure the changes in that number of patients.

It is worth noting that the findings from this study are in complete contrast to the findings of a small pilot study reported back in 2012 Wu et al. (see here). The “New” Prostate Cancer InfoLink suspects that the paper by Alibhai et al. is not going to draw this issue to a close.

4 Responses

  1. I definitely have some short-term memory impairment after about 12 months, continuing to today at 28 months … Zoladex seed injected every 4 weeks.

  2. Thanks for reporting about this important topic.

    Once again, there is an absence of evidence linking ADT to cognitive decline. That point is underlined by the nature of this study — no randomization, in conjunction with the fact that in the US ADT is used mainly as a residual therapy after primary therapy or in quite advanced cases at the outset (me). These circumstances suggest that men on ADT in the US tend to be older and therefore more firmly set in the years where cognitive decline is increasingly common, and also in a group that overall has more serious health concerns, let alone more serious prostate cancer. This study also used continuous ADT over 3 years for the ADT group, a regimen that to me seems obsolete for non-metastatic patients in view of many studies demonstrating at least non-inferiority of intermittent ADT and superior QoL with intermittent ADT.

    I did look at the earlier Wu study. While interesting as a simple probe, the self-selection methodology eliminates it from providing any meaningful insight into the extent and seriousness of cognitive decline as it relates to ADT.

    As a veteran of 14 years of intermittent ADT, including an initial round of 31 months, I suspect that ADT has no or minimal direct causative association with cognitive decline. On the other hand, I am convinced that ADT’s impact on sleep (particularly due to un-countered hot flashes and sweats) and association with heightened anxiety (due to its use in more challenging cases) do contribute to a likely decrease in top cognitive performance, unless countered by naps, exercise, anti-hot flash and sweat tactics, and so on.

    I continued working in a mentally challenging job for 5 years after diagnosis. I was able to do fine, but at times I needed naps and more exercise to keep in top shape.

  3. Jim:

    That’s all very well, but your personal experience is not the issue when others can clearly document serious problems with everything from simple memory loss to the ability to concentrate or multi-task — including much younger men than you who were extremely fit and otherwise healthy and held down highly complex jobs for years.

    Also, it would be utterly impossible to randomize men to a trial to test for cognitive decline … for the simple reason that it would be unethical to not give ADT to men who needed ADT simply to find out whether only the ones who had ADT got memory loss (while the ones who got no ADT suffered symptomatic pain and earlier disease progression).

    Difficulty establishing an evidentary basis for something that seems to happen to a significant number of patients doesn’t mean it isn’t happening.

  4. Dear Sitemaster,

    Your points are well taken, of course. I am just relating my view, taking into account cases like those you have mentioned.

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