Link between MPN and dementia

[Loooonglife]

I am not sure if this has been posted yet:

pvreporter.com/mpns-and-dem...

Link to journal article: onlinelibrary.wiley.com/doi...

[ETket]

Thank you! Not entirely cheering reading :-(.

[Loubprv Volunteer]

Hi thanks, I have had pv for going on 17 years and have def noticed a decline in concentration and memory! What joy. Apparently dancing and playing bridge are good for the brain. I dislike both.

No hope then 😂

[ainslie in reply to Loubprv]

That’s comment with MPN but is not necessarily dementia, our blood is a bit off hence the symptoms you describe

[T120 in reply to Loubprv]

Might not be what u think could be just old age I'm 75 , u r bound to forget things ,I get on computer n forget how to spells words, old age is what is the problem n there's nothing we can do about it

[lhammy66]

Having just read the statins article and thought great - then I read this one. lol. Life is a funny thing - we never really know what is going to happen but I certainly know my brain doesn’t function as well as it used to, bit of a downside for an academic. Hey ho. It’s a carry on and hope situation.

[T120 in reply to lhammy66]

More side affects in Statins than Jax 2 google Side affects, I'm allergic to them causes me to have Constine does Yr kidneys, liver, heart if u haven't had blood test to take the. Get one

[Ona54]

Hi, I am very interested in this particular topic as my husband has ET and has definitely noticed severe cognitive decline.

When I posted this article on a MPN support FB page,someone responded telling me it’s self inflicted and that people who have had unhealthy diets get dementia.

Husband has always had a healthy diet.

I hope they do more research on his.

[ETket in reply to Ona54]

What an unhelpful (and erroneous) comment to get on FB!

[ainslie in reply to Ona54]

Sums up FB , I wouldn’t bother reading MPN stuff on there

[T120 in reply to Ona54]

We all get bad memories just life, just do Yr best, n make Yr husband laugh n take him out

[EPguy]

A good find.

The plots here are a good summary. (CU is undefined MPN). The hazard ratios are not extreme in any, while ET is near 1 so didn't really add risk long term in this study.

The unanswered question is whether modern treatments now common would change this result. About half the cohort predates Jak2 discovery, and CALR for ET was not found till 2013, near the end of this study.

They note this : "We were unable to tease out treatment effects of MPN on dementia risk and cannot exclude the possibility that some treatments may have modified risk."

My thought from their report is reducing the mutation with modern treatments might be disease modifying for dementia, as below, as is known now for MPN progression etc.

--

They attribute the inflammation to the Jak2 mutation:

"Due to driver gene mutations, such as JAK2V617F, inflammation pathways are constitutively activated in patients with MPNs"

and while men were found at higher risk- "men with MPNs tend to have higher JAK2V617F allele burdens, a greater prevalence of non-MPN-specific somatic mutations (non-drivers) ..."

Consistent with all this, the HRs in the three standard MPNs in this plot correspond to mutation levels; ET-PV-MF in order tend toward higher mutations.

-So it's possible that Jak2 mutation level (VAF) is a strong correlate to this risk. Tracking VAF thru this study was not possible so we can't know directly.

They propose CHIP clinics for "CHIP-JAK2V617F positive citizens to prohibit the development of major thrombosis or inflammation driven diseases, including dementia."

CHIP is Jak2 positive but without or prior to Dx of overt MPN. Another indication the authors attribute the dementia risk to the Jak2 mutation.

--

An extra note:

"the association of MPNs on risk of Alzheimer's disease was below one" but they suspect this may not be accurate.

dem

[Bluetop in reply to EPguy]

Thanks for that analysis .

[Loooonglife]

Hi EP guy, Thanks for your thoughts. I agree it’s reasonable to assume that modern therapies should reduce the inflammatory burden and hence lower the risk of dementia, and perhaps ruxolitinib is more effective than pegylated interferons in this regard as it directly inhibits the JAK2 kinase and seems to manage disease symptoms somewhat better, in particular in situations where the molecular response is incomplete (I am speculating). Interferons can have significant cognitive side effects, such as depression. Overall, I am optimistic that both of these drugs will be shown to have benefit in delaying or preventing cognitive decline.

[EPguy in reply to Loooonglife]

Assuming the mutation is a primary driver, either IFN or Rux should help for most. But as you say, if the mutation does not respond well and all is equal, Rux might help more. Rux is more explicitly anti inflammatory; it inhibits both Jak2 and Jak1 by design. IFN is both + and - inflammatory, so its effect as we see here is less predictable.

We may get some data in coming years as more pts spend time on the modern therapies.

[ainslie in reply to Loooonglife]

Exactly , the drugs we take and imperfect blood can cause lots of similar symptoms but it may not be dementia, when I was diag in 2010 my memory, multi tasking and clarity of thought became markedly worse straight away , if that was dementia I don’t think it would have happened almost overnight and now 15 years on it’s the same, I don’t think it’s worse, I speculate if it was dementia due to MPN it would have got worse,

[ainslie]

similar has been posted before but I would urge caution before worrying.

At my yearly consult with a top exert in MPN at Mount Sinai I asked him about any link to dementia from MPN, he said in all the years he has been consulting and all the conferences he has been to and all the other MPN experts he is constantly in touch with he has never heard of such a connection. Having heard that I decided to forget about it for now, apologies for the pun.

[EPguy in reply to ainslie]

I agree it has plenty of gray, as do so many things. With HR's from 1 to ~1.5 the risk would not be obvious in case studies of real pts. But I think the results add some support to benefit of reducing the mutation.

[Bluetop]

Thanks for posting, but so useful to see EPguy's analysis too!

[Luthorville]

I wonder if CHR or partial response then reduces this risk. Thanks for sharing. Not a surprise, I'm surprised the numbers aren't worse.

[EPguy in reply to Luthorville]

If the mutation is correlated as seems the case, CHR is likely to be also since CHR and mutation reductions are related.

[Luthorville in reply to EPguy]

That would be my assumption.