From an AP news report issued today. Anecdotal evidence but nonetheless something else to put on our plates.
Alzheimer's disease may be a risk for older prostate cancer patients given hormone-blocking treatment, a large, U.S. government-funded analysis found.
Previous evidence has been mixed on whether the treatment might be linked with mental decline. But experts say the new results stand out because they're from a respected national cancer database and the men were tracked for a long time — eight years on average.
Among 154,000 older patients, 13% who received hormone-blocking treatment developed Alzheimer's, compared with 9% who had other treatment or chose no therapy, the study found.
The risk for dementia from strokes or other causes was higher: It was diagnosed in 22% of those who got hormone-blocking treatment, versus 16% of the other patients.
The results, using perhaps one of the largest and most reliable databases, suggests there truly may be a connection, said Dr. Sumanta Pal, a prostate cancer expert with the American Society of Clinical Oncology. Pal was not involved in the study.
The analysis from University of Pennsylvania researchers was published Friday in JAMA Network Open.
The results aren't proof but experts say they underscore the importance of discussing potential risks and benefits when choosing cancer treatment.
The researchers analyzed data from a National Cancer Institute database of cancer cases and treatment and covers almost 30% of the U.S. population. The study focused on men in their 70s, on average, with local or advanced prostate cancer diagnosed between 1996 and 2003. They were followed until 2013. Medicare records indicated dementia or Alzheimer's diagnosis.
Hormone-blocking treatment can include testes removal to reduce levels of testosterone, which fuels prostate cancer growth. But it more typically involves periodic drug injections or implants that achieve the same result.
Most U.S. men who receive this treatment are in their 70s or older. It's sometimes used in men who might not be healthy enough to tolerate other cancer treatments including surgery to remove the prostate and radiation.
It's unclear how the treatment might be linked with mental decline. The researchers noted that it can lead to diabetes, which also has been linked with dementia — perhaps because blood vessel damage from diabetes can restrict blood flow to the brain. Hormone treatment also raises risks for heart disease and depression, which both have been linked with dementia.
Researcher Grace Lu-Yao of the Sidney Kimmel Cancer Center in Philadelphia, said the potential dementia risks from hormone-blocking treatment may outweigh any benefit for younger, healthier patients with longer expected life spans.
While the study doesn't prove that the treatment causes dementia, she said, it is important to tell patients "because of the potential impact of Alzheimer's disease or dementia on the quality of life of patients and their family." She was not involved in the study.
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"These 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."
"Our analysis of FDA MedWatch adverse event data reports does not support the idea that androgen deprivation therapy per se is associated with Alzheimer’s disease or cognitive dysfunction."
"Among older men with low testosterone and age-associated memory impairment, treatment with testosterone for 1 year compared with placebo was not associated with improved memory or other cognitive functions."
I read a study many years ago, unfortunately I don't remember the citation, that examined the statistical reliability of medical studies. The author argued that there was a built-in bias towards publishing sensational reports. If ten studies are done examining the same topic, the one with the most sensational results was the one most likely to be published and most likely to be reported on by the press.
So far so good. But if I remember it correctly, what distinguished this particular study was that the author went on to claim that his review of the medical literature showed that European and American studies that showed a difference between a treatment group and a control group >= 1.4 to 1 were likely to be validated by subsequent research. Studies showing a smaller difference were likely to be invalidated by subsequent research. His team also did a study of Chinese medical journals and claimed that the required difference between treatment and control had to be 3:1 before the study was more likely to be validate than not.
Why are studies showing weak associations so likely to be invalid? The main reasons are errors in study design. Randomization may have been poorly done. Other factors besides the treatment may not have been properly excluded from, or accounted for, in the design. Sample sizes may have been too low - a major cause of error in that even with mice, much less with humans, costs go up with each additional subject. If we flip a fair coin 100 times, and do that exercise 20 times, the chance that one of the exercises will produce a significant difference between heads and tails will be high, much higher than the chance that would occur with 2,000 flips in one exercise.
I don't know if the study's conclusion that we need 1.4:1 to begin to have confidence in a study outcome is right. This particular study could have been wrong for all the reasons that other studies go wrong. But it contributed to my skepticism. I am reluctant to jump to conclusions after reading one study. I want to see analysis and confirmation.
We still live in an era in which important medical decisions are often based on associations rather than fully understood causes. That will change over time, but only slowly and maybe not significantly during our lifetimes.
Excellent points! There are some people on this site and similar who re-post any study without evaluation, or analysis of the level of evidence. They re-post mouse studies and RCTs as if they were equally important. Patients seeing them may become alarmed, or conversely, become sure that they've discovered a new treatment. I don't see what purpose it serves.
Researchers (the good ones) spend a lot of time worrying about the reproducibility of results. A thorough analysis includes not just "level of evidence" but "GRADE" (an evaluation of the study method). Most good journals insist on a "study limitations" section, but the abstracts usually don't contain that.
So what is the patient, who only has limited access and doesn't have the whole story, to do? One thing we can do when our information is imperfect is go through the Bradford Hill checklist. It doesn't prove causality, but can give us more confidence if we have to make a decision based on less than Level 1 evidence (large well-done randomized clinical trials). The factors that ought to be considered are:
• Strength of Association (as you correctly point out, larger associations are more likely (but not necessarily) causal)
• Consistency of Data (independent studies all lead to the same conclusion)
• Specificity (a very specific population is differentially affected)
• Temporality (the effect has to occur after the cause)
• Biological gradient (to some extent, more drug leads to more effect)
• Plausibility (one can come up with a plausible explanation)
• Coherence (lab studies demonstrate a plausible mechanism for the observed effect)
• Experiment (has the effect been prevented by modifying the cause?)
• Analogy (similar factors may be considered)
There are also many things that peer-reviewers insist upon, or should, like:
• were the objectives of the study pre-specified? (e.g., p-hacking/data mining)
• were the assumptions of the statistical technique used violated? (e.g., colinearity, unmeasured variables, lack of overlap in matched pairs, etc.)
• was the study sufficiently powered? (especially for subgroups)
• what were the sources of bias? (e.g., selection bias, ascertainment bias, high drop-out rates, conflicts of interest, etc.)
• what population, if any, can the results be generalized to?
• did the information collected allow for adequate analysis? long enough follow-up?
The point you make that the most sensational findings get published is important. Clinicaltrials.gov now insists that all posted clinical trials post the outcomes - either a link to a peer-reviewed published study or the results if a journal refuses to publish it.
We gain perspective through loses. One thing that I’m glad that I’ve lost is all inhibitions ... Today is a good day . Glad that we are still swinging and alive... can’t say that I didn’t have more fun than most in life sexually and otherwise ..I was possessed with sex from 12 to 53 .. that was a good run. I’ve accepted the back forty with a smile on my face .
I keep around people who I consider to be my friends. I think depression can occur while on ADT, but that is not dementia. My mother had dementia with loss of memory. She was 94 years old and it was hard to see her deteriorate. I am taking 100,000 units of Vit D3 a week and when I started the medication I would get forgetful for a out 2 days. It was from the calcium being released in my brain. but it has gone away now. I go to a church twice a week and have friends who know my diagnosis. I also attend 2-step meetings since 1984 and contact my sponcer or call members with questions about my behavior. This keeps me centered along with meditation and helping other people. I asked my oncologist about dementia and he said he had not heard of it from ADT therapy.
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FYI: from the VA research information on Veterans 
Latest Treatments for Advanced Prostate Cancer
