ADT and cognitive function — a review and pilot study


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.

12 Responses

  1. I hear you re multi-tasking. Two to three years ago I was on ADT for a year, adjuvant to radiation. I have to totally focus on one thing or I get distracted and forget what I am doing. A real pain and I am 49. Could be coincidence though.

  2. Mike:

    These results coincide with my experiences.

    Last year I completed a neuro-psych evaluation which clearly showed impairment in several areas.

    I began IADT at about age 51 (or so) and was really in the prime of my career.

    As a result of ADT treatment, I have had to reduce my role from a senior executive role to a much less mentally demanding job. Even in this reduced capacity I really struggle to keep up. This has had a significant negative impact on my quality of life.

    I think that as more younger men (relative term) go on ADT, you will see more situations like mine, especially in those that need to work and compete in jobs requiring a high degree of multi-tasking, concentration, and executive decision-making.

    It is a very real and serious issue (at least for me).

    Bill

  3. Re: ‘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.’

    Oh yes! A widely under-reported problem of many medications.

    As you try to hang on to the life you had, there is a lot of denial. My first impact was pain medication (a common NSAID in my case). I was very angry with people who questioned my work, relatively simple work compared to my normal tasks. It took me months to admit, yes it really was not good. I would spend all day on on a simple job, think I had it right, and in the morning see it was garbage.

    Probably harder on spouses than patients. No medication is totally free [of side effects].

    It is common to laugh about “medicine head” with common cold remedies, yet even physicians give you the”hypochondriac look” when you try to discuss confusion from medications.

  4. Last May 2, I got my last shot of a 3-year course of ADT, using the large, 12-week dose of Zoladex. I noticed some possible cognitive deficits pretty quickly. They are these: the need to focus on one thing at a time (although classical music that I was familiar with did not affect this), a slight difficulty in remembering names, a reasonably large difficulty with reading my usual number of pages at one sitting, demotivation, and a difficulty in concentrating on fiction, but none at all while reading maths. My ability at public speaking wasn’t affected.

    I read a few articles about this in medical journals but they were often pairwise inconsistent: I could draw no conclusion at all. Last week I requested a battery of neuropsychological tests (included in Sweden’s single-payer healthcare system). I told the doctor that I wished to wait a year or so for that, since the ADT had ended too recently to get any definitive results.

    There are several problems I have, one of which is mentioned in the summary above. First, I knew that it would be hard, if not impossible, to factor out the normal effects of ageing (I am 70). Second, it seemed to me that at least some of the distracting concentration, demotivation, and attention difficulties might result from tiredness and sleep-deprivation due to a low testosterone level (after an early-evening nap I felt refreshed). Third, I trained myself long ago to work hard and nearly constantly at cognitive tasks like reading and doing maths. So have I lost any of that ability? I don’t know, since I have no problems at all early in the morning. (Is my mind somehow refreshed by sleep?) Finally, the concentration and distraction issues might be partially due to a professional need to be active online almost every evening and early morning. Has that distracted me from other work that I’d rather do? I think so. I am looking forward to the tests since, besides the ADT issue, I’ve wanted to take them for years, given my scientific and philosophical interests in mind and brain.

  5. I was overjoyed to see this abstract published, first on UroToday, now here. I know exactly what Mike means when he mentioned the suspicion expressed by the physicians when trying to get help with this condition. After 2 years on Lupron (ending nearly 3 years ago), my husband’s cognition is still severely impaired and I feel he is incapable of independent living. He’s gone through the neuropsychological testing twice and occupational therapy has been of limited help. I have already printed a copy of the abstract to take with us to the next appointment with the neurologist this month.

    I cringe at the thought of this side effect having to be at epidemic proportions before anyone does anything proactive about this.

  6. Interestingly, there was an article in yesterday’s Medscape Digest on how to combat cognitive impairment from chemo: see “Cognitive training helps ‘chemo brain’ in cancer survivors“. The research suggested the role of computerized brain games. Personally, I made myself play at least one rubber of online bridge every night to keep my brain active and it helped!

    It has been suggested that “chemo brain” is a function of three co-morbidities: fatigue, anemia, and depression — all are also recognized side effects of LHRH drugs. It should be pointed out that anti-androgen drugs are really not associated with cognitive impairment, so discussing this issue in the context of ADT needs qualification. Anecdotally, I have known men switch from LHRH to anti-androgen treatment to counter cognitive side effects.

    As our venerable Sitemaster correctly points out, every man is different; some have little impairment, others are crippled — and if men are still working it can be devastating as friends of mine have discovered. Interestingly too, the time the LHRH drugs take to impact can vary a lot; some men are impaired within a couple of months while others are not impacted for several months.

    Personally, I lost the ability to multi-task, my concentration span diminished, and my memory was shot within about 6 months until a good 6 months after I came off Lupron (27 months treatment period). In recovery, most has returned … although some may suggest otherwise!

  7. The definition of the adjective venerable is supposedly, “Accorded a great deal of respect, esp. because of age, wisdom, or character: ‘a venerable statesman’.”

    I can do without the “because of age” implication … please?! I’m planning on hanging around for at least another 20 years or so.

    :O)

  8. My personal favorite is this: “Warning, do not operate heavy machinery until you know how this medication will affect you.” Sure let’s have the impaired decide if they are impaired. Can you imagine this warning on a bottle of alcohol. Plenty of people do not think alcohol effects them very much, especially while taking it. Not much different with many other substances.

    Not medical speak, but one local pharmacist said to me of one medication: “Some people can only take 10 (mg), some people can take 500 before they get wacked.”

  9. I found this comment very useful as I had often told my oncologist that my memory was getting worse and he largely ignored the comment. Not sure whether this was because he did not think there was much he could do about it, or whether he thought it was straightforward ageing. I am 72 and becoming ADT resistant so am moving on to abiraterone. Would be interested if anyone has experience of moving on to this drug and whether their memory changed (if they can remember). A lot of my problems relate to concentration. I can still play bridge but considerably worse than before. Am trying doing puzzles, etc., but anyone with any other ideas? Found the various comments excellent.

  10. The next study should interview the wives of men undergoing ADT. My husband’s cognitive impairment is so obvious and so severe that this wife simply googled “cognitive impairment and Lupron” whereupon I was presented with this and scores of other articles on the subject. My husband’s oncologist prescribed this therapy less than 1 year ago and — according to my husband — did not identify cognitive impairment as an effect. I detest this insidious treatment in which quantity of life unequivocally trumps quality. My husband’s brain and personality are so gone that last month he told me he had decided to have his testicles removed so he could stop taking Lupron injections! Hello! Are you ADT therapy advocates out of your minds? For the first time since his diagnosis just 2 years ago this month I took over the decision-making. For what it is worth, he still has his testicles.

  11. Dear Mrs Massey:

    Let me be very clear that no one I know actually likes ADT! The problem is that we have no other form of treatment that works as well as ADT as a palliative form of treatment (i.e., prevention of bone pain) for men with metastatic prostate cancer. On the other hand, there is a strong argument that way too many men either start using ADT too early (long before it is really necessary or beneficial) or they are on continuous ADT when they could have been treated effectively with intermittent ADT.

    Another problem is that the level of cognitive defect suffered by your husband is not suffered by all patients. Individual responses to ADT can vary very considerably. As we mentioned above, significant cognitive dysfunction may only affect some 25 to 30 percent of patients on long-term ADT, which is no fun at all for those patients, but does mean that 70 to 75 percent of patients are not suffering to anything like the same degree from this particular problem.

    A third problem is that we don’t know why the cognitive dysfunction occurs. Indeed, orchiectomy (surgical removal of the testes) may well have a similar effect. We don’t know this because the numbers of men who have an orchiectomy today as treatment for metastatic prostate cancer is tiny … and until relatively recently few patients would have had an orchiectomy and survived for more than a very few years.

    While I have great sympathy with your husband’s problem, it is not a problem that occurs for all men on ADT, and so there are many men who benefit greatly from this type of treatment (although it is far from ideal as a treatment for any disorder). In your husband’s case, you might want to talk to his doctors about taking him off the LHRH agonist and treating him with estrogen patch therapy instead, which can work very well for some men, and may help him to avoid at least some of the problems with memory impairment.

  12. @LE Massey

    We happened to discuss this very topic on our UsTOO advanced prostate cancer support call tonight. I encourage you and your husband to attend — please check http://www.thereluctantbrotherhood.org; the next advanced prostate cancer call will be April 6.

    These links may also be helpful:

    http://www.cancer.org/cancer/news/expertvoices/post/2012/04/09/chemo-brain-it-is-real.aspx
    http://www.cancer.org/acs/groups/content/@editorial/documents/document/acspc-031604.pdf

    You will also find good support and suggestions on the UsTOO Inspire blog.

    Onwards & upwards,

    rd

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