Cognitive Impairment from ADT and Adv... - Advanced Prostate...

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Cognitive Impairment from ADT and Advanced AR Drugs

MateoBeach profile image

Good analysis of database to estimate the neurotoxicity of hormonal treatments for PC. Takeaways 1) Yes they do cause cognitive impairment. And 2) Abiraterone +p is the only exception, reducing cognitive impairment in this analysis.

Neurocognitive impairment associated with traditional and novel androgen receptor signaling inhibitors ± androgen deprivation therapy: a pharmacovigilance study

nature.com/articles/s41391-...

Background

Conflicting evidence exists regarding whether hormone therapy for prostate cancer is associated with neurotoxicity. Thus, we aim to characterize the association between different types of hormone therapy and neurocognitive impairment in a real-world pharmacovigilance database.

Methods

We queried VigiBase, the World Health Organization’s international pharmacovigilance database, for reports of neurocognitive impairment among men who took hormone therapy from 1968 to 2021. We performed disproportionality analysis comparing rates of neurocognitive impairment with different types of hormone therapy versus other VigiBase drugs. Traditional hormonal therapy was defined as androgen deprivation therapy (ADT: gonadotropin-releasing-hormone agonists or antagonists) or first-generation androgen receptor (AR) antagonists. Novel AR signaling inhibitors (ARSIs) were defined as ARSIs with or without ADT. Differences were assessed using reporting odds ratio (ROR) with 95% confidence intervals (CI) and Empirical Bayes Estimator (EBE) values ≥1.0 signifying statistical significance.

Results

Odds of neurocognitive impairment were significantly elevated with traditional hormone therapy (ROR 1.47, 95% CI 1.34–1.62, EBE = 1.35) and novel ARSIs (ROR 2.40, 95% CI 2.28–2.54, EBE = 2.26). Odds of neurocognitive impairment were significantly elevated with enzalutamide (ROR 2.89, 95% CI 2.73–3.05, EBE = 2.70) and numerically increased with apalutamide (ROR 3.31, 95% CI 1.57–7.00, EBE = 0.98), but were decreased with abiraterone (ROR 0.68, 95% CI 0.55–0.84, EBE = 0.57).

Conclusions

This study demonstrates elevated odds of neurocognitive impairment with hormone therapy in a real-world data set. Neurotoxicity risk was higher with novel ARSIs than traditional agents, and higher with enzalutamide than abiraterone. Due to limitations inherent to disproportionality analysis (measuring associations, not risk) and incomplete data prohibiting the ability to control for factors such as age or use of secondary drugs (e.g., concurrent use of novel ARSIs with ADT), results are exploratory in nature. The amalgamation of these and other conflicting data may contribute to clinical decision-making for men with prostate cancer eligible for treatment with these therapies, especially those with significant neurologic comorbidities.

66 Replies

Most anyone who has been on ADT can vouch for the dreaded brain fog. I used to test myself by trying to recall a 4 digit code for 10 seconds. At the worst point I could only remember 2 of the digits. Now I can easily recall 8 digits.

Fascinating that abi might help your brain. I wonder why? Is this a new super brain drug that will soon be the rage at college campuses? I wonder if it has anything to do with my 8-digit recall and the fact that I have a better memory than my 17 year younger wife? (I take abi to underlie BAT)

Now I know what the drug was in the movie Limitless.

PBnative profile image
PBnative in reply to RSH1

I bet it’s the prednisone

Scout4answers profile image
Scout4answers in reply to RSH1

Limitless- My favorite movie... 1st 1/3 anyway, then it got dark.

RSH1 profile image
RSH1 in reply to Scout4answers

Agreed. However, I was expecting the typical dark ending. Drugs and trying to exceed your limits. Usually, that calls for some kind of thinly veiled warning. I was surprised by the Limitless ending.

The message seemed to be: stay in your cozy little mediocre box but if you go outside it, give it your all if you want to get it all.

Haha Scout, got dark because he got greedy. Great movie!

I would take that drug in a heart beat.

I would run marathons again and my husband would start competing world bench press, we would be a super couple..lol dream on!!!

RSH1 profile image
RSH1 in reply to Miomarrito

Got dark because he only got 75% greedy. At the end he went 100%. Synapses rewired permanently and he won big. Loved the fact that it didn't end with a lame drug warning.

j-o-h-n profile image
j-o-h-n in reply to RSH1

8 digits? That's nuttin..... I can recall my land line telephone number (including the country code 1 and the separating dashes or periods)....

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 05/03/2022 7:22 PM DST

Miomarrito profile image
Miomarrito in reply to j-o-h-n

I got you beat I know my grandmoms. HI 9-8115. Lol she’s been gone forever!

j-o-h-n profile image
j-o-h-n in reply to Miomarrito

Very strange..... I found that telephone number in my grandfathers wallet, she must have been beautiful cause he only liked lovely women..................(???)

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 05/03/2022 8:25 PM DST

RSH1 profile image
RSH1 in reply to j-o-h-n

Lol!!!

Boywonder56 profile image
Boywonder56 in reply to RSH1

Class !!!......pay attention

With everything that all of us are going through, or have been through, it’s just so wonderful to smile and laugh… loving this group !

RSH1 profile image
RSH1 in reply to j-o-h-n

Long term memory is interesting. I remember the phone number to the house I lived in when I was 6.

But what I meant was that I can look at an 8 digit code for a couple of seconds and then it is committed to memory (part of a secure login system - when I was on ADT I would have to try to memorize 2 digits, switch sites, enter those, go back....).

j-o-h-n profile image
j-o-h-n in reply to RSH1

I have a hobby of researching immigrants (usually notable people or relatives of friends of mine) and document the notable ones in an email to the Ellis Island Foundation. Part of the documentation is including "the passenger number" which I have to enter part of the number several times to get the full number.

Now for a trivia question.... In the old days telephone numbers included a sort of an area alphabetic prefix in the telephone numbers: e.g. CY2-0966 stood for CYpress2-0966. There was a Group* of people who were opposed to replacing the alpha CY to digits 292-0966. (And of course Pennsylvania 6-5000 Song by Glenn Miller)

Now here it is, what was the name of the *Group?

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 05/03/2022 10:51 PM DST

RSH1 profile image
RSH1 in reply to j-o-h-n

The stickinthemudlets?

j-o-h-n profile image
j-o-h-n in reply to RSH1

Close but no cigar........... (however a perfect name for my ex-wife's family)...See cancerfox's perfect answer....

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 05/03/2022 11:18 PM DST

Miomarrito profile image
Miomarrito in reply to j-o-h-n

Oh my gosh, I’m laughing again!

cancerfox profile image
cancerfox in reply to j-o-h-n

The Anti-Digit Dialing League was against the elimination of prefix names.

j-o-h-n profile image
j-o-h-n in reply to cancerfox

B I N G O!!!

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 05/03/2022 11:16 PM DST

RSH1 profile image
RSH1 in reply to cancerfox

What did they have against fingers and toes? How would we count without them?

Miomarrito profile image
Miomarrito in reply to RSH1

After reading all of your comments, I asked my husband if he was feeling some brain fog or forgetfulness…His reply was sometimes. I am feeling like he doesn’t want to tell me everything😥

Glad to hear you are laughing again. I was going to suggest that for you both. The challenges of dealing with cancer requires humor. Sometimes irreverent but never disrespectful. And remember that some of us enjoy digging into the deep end of biology and physiology. What is important is not complicated I’m the end. Paul

I agree Paul, respecting both❤️

RSH1 profile image
RSH1 in reply to Miomarrito

Sometimes my wife would trade places with you. I divulge EVERYTHING!

A review of prostate cancer treatment impact on the CNS and cognitive function | Prostate Cancer and Prostatic Diseasesnature.com/articles/s41391-...

My MO is probably going to recommend an ADT holiday for me soon once I complete another CTC blood test and another PSMA scan, this time a Pylarify, over the next couple of weeks. She already stopped the lupron (going on two months since my last injection expired. Currently still on abiraterone and dexamethasone. She feels I have a good chance of remaining undetectable for a long time after stopping adt and that the benefits of flooding my system with testosterone, reducing the brain fog and cardiovascular risks are worth it.

She told me of one rather rich and famous patient of hers with Stage IV mPCa who died due to dementia associated with ADT.

DarkEnergy profile image
DarkEnergy in reply to 6357axbz

We are all an experiment of one, so to compare others to our reaction of ADT administration is futile.

We are yet to understand how our brains are wired, for an oncologist to suggest how we react to drugs is beyond reality.

The Oncologist acts based on historic reaction on how ADT affects our prostate cancer treatment from hormone therapy, nothing more, nothing less.

6357axbz profile image
6357axbz in reply to DarkEnergy

The anecdotal evidence for ADT related “brain fog” is, I believe, overwhelming.

DarkEnergy profile image
DarkEnergy in reply to 6357axbz

Agreed, my point - "brain fog" - is not an actionable diagnosis for disability.

6357axbz profile image
6357axbz in reply to DarkEnergy

What do you mean by “for disability.”

DarkEnergy profile image
DarkEnergy in reply to 6357axbz

USA Social Disability benefits, I'm stage 4 Cancer, but my treatment is working, so not disabled. Unfortunately, hormone therapy that causes brain impairment is not a disability, sans the rules.

No, that’s for polite company. However “iatrogenic cognitive impairment “ may be.

RSH1 profile image
RSH1 in reply to DarkEnergy

I'm not sure what you mean? Why shouldn't we expect our doctors (and others) to have an opinion on how we might react to a given drug?

MateoBeach profile image
MateoBeach in reply to 6357axbz

Sounds like you got a very good MO. Testosterone restoreth what ADT takes away. At least to a good extent. Good luck

6357axbz profile image
6357axbz in reply to MateoBeach

I hope so, thanks Beach!

RSH1 profile image
RSH1 in reply to MateoBeach

I'll one up you on that. Testosterone restoreth me to my 30's. Love, love, love testosterone and nandrolone. And SARMs save the ADT day. I'm 60 and haven't been in this kind of shape for decades (surprise, surprise, I did a 3-month cycle of nandrolone when I was 38 and was "in").

GeorgeGlass profile image
GeorgeGlass in reply to 6357axbz

What is your psa doubling time when not on adt? What is your current psa?

The following turned up on PubMed this morning:

"Androgen Deprivation Therapy and the Risk of Dementia after Treatment for Prostate Cancer" [1]

I decided not to post it, but you have forced my hand. lol

For a moment, I thought I would post it along with the recent:

"Antiviral, immunomodulatory, and neuroprotective effect of lithium"

It's an amazing drug & might inhibit the onset of dementia.

"On the clinical level, some preventive action against dementia and moderately therapeutic activity in Alzheimer's disease, and mild cognitive impairment were observed."

For those concerned about the negative cognitive side effects of ADT, take a look at the lithium literature on PubMed.

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/348...

[2] pubmed.ncbi.nlm.nih.gov/353...

LearnAll profile image
LearnAll in reply to pjoshea13

Lithium is the first psych med which have been used for over hundred years for Bipolar Disorder and schizophrenia. It is very effective for these disorders BUT it has a lot of bad side effects such as serious weight gain, sleepiness, etc. Also if one by mistake takes higher dose ,it can cause kidney failure and the person can go in coma. Lithium toxicity can rarely cause death.... So it is safer to tolerate some forgetfulness and not use lithium.

Boywonder56 profile image
Boywonder56 in reply to LearnAll

Can i chew on lithium batteries.......🤪

LearnAll profile image
LearnAll in reply to Boywonder56

Na..na.na..na NYET.

j-o-h-n profile image
j-o-h-n in reply to Boywonder56

WOW I never heard about anyone chewing on batteries. However, when I was 16 years old I dated a girl who wanted to eat light bulbs. While in her bedroom she use to tell me if I turned off the light she would eat it. By the time I figured what she meant I was personal non grata since her Dad found us in bed and asked what we were doing there. I said we were only "necking". He told me to put my neck back in my pants and never to set foot in his house again...... (yep I was just in time to be too late)...

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 05/04/2022 7:04 PM DST

CAMPSOUPS profile image
CAMPSOUPS in reply to j-o-h-n

If Svengoolie wasn't a family show you could sell them that one lol.youtube.com/watch?v=g-4-gLl...

j-o-h-n profile image
j-o-h-n in reply to CAMPSOUPS

A rim shot is much better than a grim shot......

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 05/04/2022 10:15 PM DST

For me this isn't actionable. But if I wanted to research this I might start with ACTH.

Adrenocorticotropic Hormone Protects Learning and Memory Function in Epileptic Kcna1-null mice - PMC

ncbi.nlm.nih.gov/pmc/articl...

Abi increases ACTH (prednisone is used, in part, to reduce it to normal levels).

I am having Degarelix as my ADT to avoid memory fog.

The first 6 months of my ADT experience (part of clinical trial) was Eligard with abiraterone +prednisone. The remaining year was still Eligard minus the abi and pred. I don’t know if the combination was better tolerated-in every aspect-or not. It certainly seemed that way.

I’ve always assumed the side effects (including brain fog) were simply ADT cumulative, but perhaps it was the initial abi/pred that mitigated them on that front end.

I do know that plenty of cardiovascular and weight training eliminated or sharply lessened all the sides throughout -the fog, the fatigue and the sarcopenia particularly. I can’t conceive of what it would have been like if I’d not been dedicated in that regard.

The only exception was blood pressure-elevated, but returned to normal after ADT.

With the combo of firmagon and xtandi I experienced conciderable cognitive issues. Now I am using orgovyx and nubeqa, and the cognitive SEs are much more tolerable.

MateoBeach profile image
MateoBeach in reply to joeguy

Good to hear, joeguy.

Any views on whether there is lasting impact after you stop adt, or do you return to normal?

MateoBeach profile image
MateoBeach in reply to Tony666

For me, when off ADT and on testosterone, I am definitely more clear headed, but not back to normal. My verbal recall is still slower than my normal, and learning new vocabulary requires repetition that formerly I did not require. But my understanding of even complex subjects, and ability to analyze, etc. seem as sharp and deep as ever. Better judgement comes with age and maturity. Let’s call that wisdom, if I may, and is not impaired by ADT or chemo-brain. (Then again, perhaps I’m delusional). 😆

RSH1 profile image
RSH1 in reply to Tony666

I guess we're all different in this regard. I stopped ADT and went on testosterone and my mental faculties came back rapidly. I don't think it took longer than a month. But I was only on ADT therapies for 6 months.

I’m on Xtandi pills and estradiol patches. Always tired. Is there any way to fight the fatigue other than exercise?

MateoBeach profile image
MateoBeach in reply to Break60

Two possible thoughts for consideration. 1) Ask if you can switch to Nubequa from the Xtandi. 2) Trial of dexmethylphenidate, (a mild stimulant used for PTSD. Focalin) 5mg twice daily to start.

Break60 profile image
Break60 in reply to MateoBeach

I just googled nubequa ; says it’s for nmcrpca. I have mcrpca unfortunately. But I’ll still call my MO. Because I’m a zombie. I’ll start a new thread.

RSH1 profile image
RSH1 in reply to Break60

My MO prescribed Zytiga for me back in early 2019. It wasn't approved at that time for nmHSPC. But she knew what it would do. So she figured out a way to get me on it. God bless her.

Bayer's Nubeqa one step closer to blockbuster status thanks to FDA priority review in potential new use | Fierce Pharma

fiercepharma.com/pharma/pri...

Thanks for the suggestions. I’ll call my MO.

Thank you!

Would orchiectomy have a lesser effect ?

MateoBeach profile image
MateoBeach in reply to alperk

No measurable difference in cognitive impairment for dementia that I could find. However it seems orchiectomy has significant lower risks in other areas:

jamanetwork.com/journals/ja...

6357axbz profile image
6357axbz in reply to MateoBeach

BUT…cut em off and the only way you’ll get significant levels of testosterone is artificially via injections

RSH1 profile image
RSH1 in reply to 6357axbz

Unless of course you glue them back.

Ty for posting mb...confirms my suspicions of my double blockade lupron / erleada...an aplutimide wich passes blood barrier in brain...and i understand enzlutimide does not...but ci is higher...if i read right....but both suck.....

Xtandi was added to my estradiol patches about six weeks ago as my psa had climbed from nil to .8 over three years which led me to have a dcfpyl psma ct pet scan . It found small bone mets. I’ll have psa checked again later this month . I have really been tired on Xtandi. On top of that I’m totally incontinent. And to boot my wife had a cerebral hemorrhage in January and now lives in a wheelchair. I wonder if I should switch to abi? Bob

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