July 3, 2019

expert reaction to study looking at androgen deprivation therapy for prostate cancer, and risk of Alzheimer’s and dementia

Research, published in JAMA Network Open, reports an association between a prostate cancer treatment (ADT) and being diagnosed with Alzheimer’s disease.

Prof Nicholas Mottet, Chair of the Prostate Cancer Guideline Panel for the European Association of Urology, said:

“The topic is relevant, as some previous cohorts suggested a link between ADT and decreased cognitive function.  Here we are dealing with more precise definition: Alzheimer’s and dementia.  The results are in line with almost all previous papers dealing with this subject.

“The methodology is clear, robust, with a major intrinsic limitation: working on a data-base NOT designed to answer this specific question is always an issue.  This is especially true for the MEDICARE coding, which is not a clinical ‘trial like’ coding.  Especially without any data quality control.  Furthermore there is no clear definition on how the diagnosis of both clinical situations was done (outside coding which might be partly artificial and not representing the full clinical reality).  The fact that the coding seems to be clinically relevant (as stated by the authors for both diagnostics) is not enough to consider this finding as high-level evidence.

“The most important limiting factor I would consider here, apart from the previous point, is the lack of data on other potential causes of dementia, Alzheimer (such as vascular).  Just dealing with Charlson comorbidity index is not enough.  As said by the authors themselves, the two cohorts are quite different.

“This is another paper suggesting such a link, without yet any potential causality detailed.  It emphasises the need for prospective well designed cohorts with diagnostics based on accepted definitions.  It highlights again, if needed, that there is a toxicity with ADT apart from bone, muscle and the metabolic syndrome.  ADT should be reserved for those really in need for such a treatment based on evidence, and should never be used just to lower the PSA.  No this trial is not a level 1 evidence that ADT leads to dementia, but is another piece or information suggesting again that we need to balance the decision to use (benefits) with side effects.”

Dr David Montgomery, Director of Research at Prostate Cancer UK said:

“Hormone therapy is a highly effective treatment for prostate cancer and can keep the disease at bay for many years.  While we know it can be associated with a number of side effects, we would not encourage men to change their treatment as a result of this study alone.

“This fairly large study ties in with existing research on the topic and seems to show a slightly increased risk of dementia in men on a particular type of hormone therapy called ADT.  However, this study does not show that ADT causes dementia, and there may be other reasons that the men chosen for this treatment might develop dementia.

“More now needs to be done to understand the relationship between long term ADT treatment and dementia.  In the meantime, Prostate Cancer UK will continue to fund research to ensure men get the best treatments for prostate cancer.”

Dr James Pickett, Head of Research at Alzheimer’s Society, said:

“This robust study suggests, for the first time, that this prostate cancer treatment could be linked to an increased risk of developing dementia.  In fact, it finds that for every 10 men receiving androgen deprivation treatment (ADT), one more might develop dementia than if they weren’t taking the treatment at all.

“But it does not address why ADT might influence dementia risk and cannot prove that it contributes directly to the development of dementia.  There is some evidence that ADT increases the risk of heart disease, diabetes and stroke, which are all known risk factors for dementia.  There are also important caveats – those who received ADT were more likely to be unmarried and from poorer areas in the US – so further research into this link should be prioritised.  Examining medical records has tremendous power to identify unknown links between medications and people’s health which is why we’re currently funding research to find drugs that may increase or decrease the future risk of dementia using NHS records.

“ADT remains an important treatment for some men diagnosed with prostate cancer.  Yet this is a large and well controlled study, and so this new evidence should be included in discussions about the risks and benefits of the treatment.”

Dr Sara Imarisio, Head of Research at Alzheimer’s Research UK, said:

“This study is part of an active area of research into the role that sex hormones like testosterone could be playing in the brain in dementia.  Studies like this, which take advantage of the rich data held in medical records, can be very useful for highlighting trends and potential risk factors for further research.

“Previous research into the relationship between androgen deprivation therapy and dementia risk has been conflicting, but this large, long-term, well conducted study represents strong evidence in support of a potential link.

“While these results suggest an association between androgen deprivation therapy and an increased risk of dementia, they do not show that ADT is definitely causing this increased risk or how this therapy could be affecting the health of the brain.  We need to better understand the impact of sex hormones in the brain in diseases like Alzheimer’s to delve deeper into the possible reasons for this link.

“In the meantime, it is important to bear in mind that prostate cancer is a serious disease and any possible risks of ADT need to be carefully weighed against its role in treating prostate cancer.  If anyone receiving ADT has any concerns, they should seek advice from their doctor.”

Prof Martin Rossor, NIHR National Director for Dementia Research, University College London Hospitals (UCLH), said:

“Hormone therapy to reduce testosterone is an important treatment for prostate cancer and there have been concerns that this may cause problems with memory.  This large study suggests that elderly men on hormone therapy for prostate cancer are more likely to be diagnosed with Alzheimer’s disease or dementia over the next ten years than those not on hormone therapy.  This study is important for helping to understand risk factors for dementia, but the association does not prove a direct link.  Diagnoses of dementia are common in the elderly anyway, and the additional risk observed in this study is small.  It is important that men with prostate cancer get the best treatment for their cancer.”

* ‘Association between androgen deprivation therapy use and diagnosis of dementia in men with prostate cancer’ by Ravishankar Jayadevappa et al. will be published in JAMA Network Open at 16:00 UK time on Wednesday 3 July 2019, which is also when the embargo will lift.

DOI: 10.1001/jamanetworkopen.2019.6562

Declared interests

Dr Sara Imarisio: “No conflicts to disclose.”

Prof Martin Rossor: “No conflicts.”

None others received.