XRT for Alzheimer's dz

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IonsAreOurFuture

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As mentioned in another thread, multiple case reports and animal studies are showing a benefit to relatively low dose RT in Alzheimer's dz. Sometimes amyloid plaques are disappearing and memory is improving (animals), and sometimes memory is improving without a change in amyloid burden. Earlier in the disease is thought to be more beneficial time to intervene than late/advanced stages.


There is an interesting case report from a woman in Michigan on hospice for Alzheimer's who got 5 CT scans to the brain and went from essentially mute and wheelchair-bound to interacting with people again:


There is now an FDA-approved diagnostic test, Lumipulse, that detects the abnormal amyloid isoform 42 in the CSF. Having a biomarker (like PSA) is really important for making progress with a disease, but the jury is still out if reducing a surrogate like amyloid is enough to justify a therapy, as shown by the controversial Aduhelm FDA approval. It didn't help that Biogen wanted to charge $56,000 for a year of anti-amyloid monoclonal Ab. Lumipulse may be able to eliminate the need for some brain imaging at diagnosis but does require a lumbar puncture:


Nobody seems sure how the radiation may be helping, but immuno-modulation may be part of it because microglia levels (brain macrophages) and polarization (M1 to M2) change after XRT, sort of how low-dose XRT changes the tumor microenvironment in Radscopal.



Any interest in a trial?
 
Any interest in a trial
YAWN. - academic rad oncs

But seriously. We should. But would be nice to do it smartly. I think the Beaumont study that shut down looked at 10 Gy in 5 fx. That is probably overcooking it (but to the average academic rad ONC is “low dose”). The trial should start with arthritis level doses, or 50% of traditional arthritis doses.

EDIT: also may not be advisable to forget the physics, and radbio (proportional to Z cubed, some RBE differences), of kV X-rays from CT scans *if* a linac trial were negative
 
Yes, we should try to attempt this.
However, I would not be overenthusiastic about this. We have attempted low-dose WBRT for MS too. It didn't work out well.

There are so many things to figure out: Timing, Dose, Fractionation. And indeed not all Alzheimer's disease may be of the same type / pathology, thus results may vary.
 
Agreed that Dementia diagnosed as Alzheimers likely represents a very heterogenous population and set of pathology, and as such any potential benefit would be unlikely in all people.

But we know in general terms the impact of ionizing radiation on human brains. And if you give, say 20 cGy x 5 to a brain expecting a 25% chance at improvement, what expectation for harm would we have?
 
Agreed that Dementia diagnosed as Alzheimers likely represents a very heterogenous population and set of pathology, and as such any potential benefit would be unlikely in all people.

But we know in general terms the impact of ionizing radiation on human brains. And if you give, say 20 cGy x 5 to a brain expecting a 25% chance at improvement, what expectation for harm would we have?
Very little harm, indeed. But we certainly need to work on the dose issue.
 
"Doc, you radiated my 90 year old grandmother for Alzheimer's and she still can't remember ****!"
"Sure, but imagine how bad her memory would be if she HADN'T received radiation!"
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Does everyone need to be on memantine to begin with or nobody on memantine? I feel like it's a hippocampus sparing study in reverse!
 
Sorry but this is another indication Urology has dibs on.

Sildenafil was initially developed as an anti hypertensive (still used as one too, especially for pulmonary HTN). Whoever noticed male patients were getting chubbies and put 2 and 2 together is a GD genius. Osterloh gets all the credit but I highly doubt it was the PI who really noticed what was going on. Gotta wonder how many meaningful discoveries have been missed or discarded because they were not part of the trial objectives.
 
Sildenafil was initially developed as an anti hypertensive (still used as one too, especially for pulmonary HTN). Whoever noticed male patients were getting chubbies and put 2 and 2 together is a GD genius. Osterloh gets all the credit but I highly doubt it was the PI who really noticed what was going on. Gotta wonder how many meaningful discoveries have been missed or discarded because they were not part of the trial objectives.
My understanding is that sildenafil was being explored as an anti-altitude sickness medication when the mountaineers they recruited for the study started reporting that interesting side effect.

That’s the story I heard at least. Probably was happening at the same time as the other stuff.
 
My understanding is that sildenafil was being explored as an anti-altitude sickness medication when the mountaineers they recruited for the study started reporting that interesting side effect.

That’s the story I heard at least. Probably was happening at the same time as the other stuff.
Had heard it was being noticed in tubed ICU patients being treated for pulmonary htn
 
Identified during phase 1 trials looking at it for pulmonary htn and angina, though there were already thoughts at Pfizer that it might help in ED

 
Alzheimer's may be linked to cytomegalovirus, a herpes family virus, in many cases.



This is intriguing... because radiation is very effective at treating warts, and shingles.

Thanks for sharing that. It makes some sense, and I think I've seen it hypothesized that a nasal virus could be one underlying cause or risk factor.

There is a possible pathway of spread, just like herpes, from the nose to the olfactory nerve, to the entorhinal cortex, to the hippocampus, and then lateral temporal lobes.

It has gradual prion-like spread, eventually going to all the other parts of the cerebral cortex.
 
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