Hi j11,J11 wrote:...A futile futility analysis?...
This is amazing!
Where is everyone on this?...
Unending exhortations for yet more money with little actual evidence of progress eventually wears down everyone. If we finally have something the financial resources of the dementia community can flow into researching an effective treatment.
Great question on the 26-week effect! If only we could get in the room and ask the researchers!! Check out pp 21 and 22 of the report. They seem to show a turning point for tau reduction and also for reduction in the rate of decline on the CDR-SB (a measure of AD progression) around week 26 also. Here's a wild speculation: It takes about 26 weeks to reduce the level of beta-amyloid in the brain to a sufficient level that other compensatory mechanisms, including reduction in tau, better cerebral metabolism, preservation of neurons, etc. can begin to exponentially improve.J11 wrote:One of the great ironies here of course is that the Alzheimer epidemic has actually now gotten worse.
Extending out the time caregivers need to care for those with clinical dementia adds to their burden.
I notice in the Biogen url that you included that the low dose and high dose in Emerge and Engage had exactly the same amyloid
trajectories until week 26. I find it odd that they would continue giving the high dose during this time. What this seems to be telling me is that the brain can only process so much amyloid over the first few months no matter how high the dose. If this is true, then why would a patient want to take the high dose and perhaps expose themselves to ARIA without any benefit?
J11 wrote:NF52, what report are you referring to with pages 21 & 22? The Biogen url that you cited only went to page 17.
Sorry about that! I copied the wrong url. Here's the correct one:
The high dose was pre-specified so this is not cherry-picking. It also appears that ADL-MCI is the most sensitive (and for caregivers and families probably the most relevant) of the measures; so the other measures probably did not score even lower simply because they did not have the validity to do so.
...ITT is only intent to treat not actual treatment, so even the MMSE miss is hardly relevant. Good point; I noticed that also. Even for people who did not complete the 78 week trial, and even including those who dropped out at any point, the benefits appear similar. Maybe the occur primarily in the first year (52 weeks). Figuring out how long someone needs to be on the drug, especially if it is approved for prevention, not treatment, is a significant need.
...I am also trying to think through what is happening during those first 26 weeks. The analogy
of driving on the freeway might be handy. When the flow of traffic is 50 miles per hour, it does not matter
what you do, you will move with this flow and travel at 50 mph. Possibly same with amyloid, you can
go low dose you can go high dose, though for the first 26 weeks it does not appear to matter you will
have the same amyloid reduction....if you try to push through the flow of traffic...you increase danger without actually increasing your speed (with amyloid this would mean ARIA). I like this analogy; you have to manage the congestion before the efficiency of any traffic system is evident.
... What I understand for the result from this trial is... this really should imply lower dosing combined with a longer trial, say 30 months instead of 18 might become the standard...It really is not that low dose was not effective, it was more that the blue lines had not yet caught up with the green lines in amyloid reduction. Another great observation!
...All those other add-ons that those on the forum have been trying could have a better chance at being effective without having to compete against a relentless neurodegenerative process. It will be the next wave of research that allows for even earlier treatment that will result in a noticeable inflection of the dementia crisis.
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