Alzheimer’s, dementia, and androgen deprivation therapy (again)


A new study has concluded that added risk for Alzheimer’s disease and dementia among Medicare patients with prostate cancer who were treated with androgen deprivation therapy (ADT) was minimal in men treated between 2001 and 2014.

The new paper by Baik et al. has recently been published in the Journal of Clinical Oncology, and was also discussed on the Medscape web site yesterday.

Basically, Baik et al. used information on men of 67 years and older from the Medicare database (between 2001 and 2014) to explore the relative risk for Alzheimer’s disease among men with prostate cancer who had also received androgen deprivation therapy (ADT) for treatment of their prostate cancer.

They found the following:

  • 1.2 million fee-for-service Medicare beneficiaries developed prostate cancer between 2001 and 2014.
  • 35 percent of these 1.2 million men (i.e., about 420,000 men) received ADT.
  • Of these roughly 420,000 men,
    • 109,815 developed Alzheimer’s disease.
    • 223,765 developed dementia.
    • 26 to 33 percent died without any sign of either condition.
  • Initial, unadjusted rates of Alzheimer’s disease were
    • 17.0 per 1,000 person-years in ADT recipients
    • 15.5 per 1,000 person-years in the men who didn’t get ADT
  • Initial, unadjusted rates of Alzeimer’s-related all-cause mortality were
    • 73.0 per 1,000 person-years in ADT recipients
    • 51.6 per 1,000 person-years in the men who didn’t get ADT
  • Initial, unadjusted rates of dementia were
    • 38.5 per 1,000 person-years in ADT recipients
    • 32.9 per 1,000 person-years in the men who didn’t get ADT
  • Initial, unadjusted rates of dementia-related mortality were
    • 60.2 per 1,000 person-years in ADT recipients
    • 40.4 per 1,000 person-years in the men who didn’t get ADT

However, after analysis was adjusted to take account of other cancer therapies and other co-variates:

  • Men treated with ADT
    • Had no increase in risk of AD (subdistribution hazard ratio [SHR] = 0.98)
    • Had a 1 percent increase in risk of dementia (SHR = 1.01)
    • Were more likely to die before progression to Alzheimer’s disease (SHR = 1.24)
    • Were more likely to die before progression to dementia (SHR = 1.26)
  • The risks of Alzheimer’s disease and dementia were not associated with duration of ADT (i.e., there was no dose effect)

The authors note that other secondary analyses confirmed these results, and they go on to conclude that their data

suggest that ADT treatment has no hazard for [Alzheimer’s disease] and no meaningful hazard for dementia among men age 67 years or older who are enrolled in Medicare.

However, it is clear that the controversy over whether ADT increases risk for Alzheimer’s disease and dementia among prostate cancer patients isn’t going to go away any time soon (see this editorial by Dr. Kevin Nead in the same issue of the Journal of Clinical Oncology), and there is clear evidence of an impact of ADT on cognitive function in at least a subset of patients on long-term ADT.

One Response

  1. Possible Explanations for the Very Low Risk Found in this Study

    Wow! Impressive study — thanks (again) for bringing it to our attention!

    This study is consistent with what I expect — no or weak association — having followed this issue of ADT and dementia/Alzheimer’s as a very interested party, having been on ADT intermittently from late 1999 through April 2014.

    Proxy Versus Cause: What may be happening is that ADT is a proxy, in the US at least, for men who are older, who also have more health challenges, and who therefore are more prone to Alzheimer’s, but who also are more prone to shorter survival for the same reasons, thereby shortening their exposure to the dementia/Alzheimer’s prone years, which would result in fewer diagnoses of dementia/Alzheimer’s. These would be cross-cutting factors, and quite possibly independent of ADT use. It will be interesting to see how these researchers controlled for these factors in the study. I suspect they did a very good job.

    Countermeasures and Dementia/Alzheimer’s: Also, well-done ADT involves employment of a number of countermeasures to prevent or reduce likely side-effects, and some of these countermeasures are associated with reduced risks of dementia and Alzheimer’s. Without checking carefully, I suspect that a good diet (such as Mediterranean, Asian, vegan), weight control, and exercise are among the countermeasures that would lower the risk of dementia/Alzheimer’s. Unfortunately, the big data data sets do not capture that kind of information. Also unfortunately, my strong impression is that too few patients on ADT employ these countermeasures as they should.

    While the Medscape link comment on the editorial noted the editor’s view that evidence of association between ADT and dementia/Alzheimer’s was building, my strong impression is that much of this evidence is poor quality in that it did not address the critical fact that ADT use is a proxy for older men and more comorbid conditions, factors that are associated with dementia/Alzheimer’s.

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