Alzheimer's Disease Cured ! J11 Exclusive!

Alzheimer's, cardiovascular, and other chronic diseases; biomarkers, lifestyle, supplements, drugs, and health care.
J11
Contributor
Contributor
Posts: 3357
Joined: Sat May 17, 2014 4:04 pm

Alzheimer's Disease Cured ! J11 Exclusive!

Post by J11 »

Alzheimer's Disease has been cured!

Evidence reported at CTAD 2023 shows early stage Alzheimer's patients (i.e., those who were 2 years before the average patient in the TB-2 trial for Donanemab) had a 95% slowing of disease progression over 18 months as measured by CDR-sb (88% as measured by iADRS). In our experience 95% slowing especially if extended out past 18 months which is what we have seen occur with such responders such as with Aducanumab and we are seeing emerge with Lecanemab and Donanemab constitutes a functional cure. Considering that all Alzheimer's patients at some point would be pre-AD patients, this opens the possibility that preventative treatment should stop the AD pandemic.

Any remaining rebuttals concerning efficacy questions for mabs are now quickly losing all reasonable basis for consideration.

AD has had a large impact on my life and it is a great honor for me to now make this information more widely known. I was somewhat surprised recently when this monumentally important development did not seem to have reached those on forum so I wanted to reach out to those who might be unaware of this by posting a dedicated thread. Please refer to the main Celebration Thread for Aducan for more detailed discussion.



https://assets.ctfassets.net/mpejy6umgt ... ersion.pdf

(Reference above is page 35 for the figure below)


https://www.desmos.com/calculator/2229w9nw9j
The desmos url provides a graphical representation of how treatment response declines with
increasing disease severity. Notice that 2 years before the average patient in TB-2 disease slowing is ~ 95% and
2 years after the average patient disease slowing is 8%.

Disease Time CDR-sb.PNG
Stage Benefits.PNG
You do not have the required permissions to view the files attached to this post.
KathleenC
Contributor
Contributor
Posts: 41
Joined: Thu Jun 08, 2023 10:22 am

Re: Alzheimer's Disease Cured! J11 Exclusive!

Post by KathleenC »

Thanks so much for sharing this information!
User avatar
Tincup
Mod
Mod
Posts: 3592
Joined: Fri Aug 08, 2014 2:57 pm
Location: Front Range, CO

Re: Alzheimer's Disease Cured! J11 Exclusive!

Post by Tincup »

Why is "slowing of disease progression" considered cured?

Dr. Bredesen's approach actually reverses (for a lot less $$).
Tincup
E3,E4
User avatar
TheresaB
Mod
Mod
Posts: 1676
Joined: Wed Feb 03, 2016 9:46 am
Location: Front Range, CO

Re: Alzheimer's Disease Slowed ! J11 Exclusive!

Post by TheresaB »

J11

Alzheimer's disease has not been cured. In the future please be more cautious about promoting information that is misleading, providing undue hope.
-Theresa
ApoE 4/4
User avatar
Julie G
Mod
Mod
Posts: 9205
Joined: Sat Oct 26, 2013 6:36 pm

Re: Alzheimer's Disease Slowed ! J11 Exclusive!

Post by Julie G »

While we appreciate your enthusiasm, J11, there is currently no cure for Alzheimer's disease. There are treatments that may change disease progression, and drug and non-drug options that may help treat symptoms. If and when that changes re. Alzheimer’s, it will make national news and we will all be celebrating with you. :D

I gently encourage you to remain curious and humble per our community guidelines when posting on the forum, especially with regard to a medication that is potentially harmful to our population. While this latest model looks promising, we don’t know the long-term effects.
J11
Contributor
Contributor
Posts: 3357
Joined: Sat May 17, 2014 4:04 pm

Re: Alzheimer's Disease Cured ! J11 Exclusive!

Post by J11 »

Kathleen C, thank you for your post!

Yes, I thought some would not be aware of this recent development.
I think that it is extremely important that we fully appreciate the current treatment landscape.

What we know now is that the endlessly repeated percentages for disease slowing variously reported in different studies as 22%, 27%, 36%, etc. have been very misleading. These toplines are actually averages of patient subgroups that had responses ranging from near 0% to near 100%. It should be understood that early MCI ( and earlier) are typically expected to demonstrate substantial improvement versus placebo. This is of great practical importance because even now many might think that the benefits involved might not be that great and that they would prefer to wait. Yet, as we know waiting even a year for some patients would greatly diminish their clinical outcomes. It would be very helpful if additional safety studies might be done with these patients.
J11
Contributor
Contributor
Posts: 3357
Joined: Sat May 17, 2014 4:04 pm

Re: Alzheimer's Disease Cured ! J11 Exclusive!

Post by J11 »

Tincup, I went with cured and not slowing of progression because the slowing of progression reported for the early MCI patients was 95%. At some point slowing no longer seems the correct term -- here we are seeing essentially the end of progression. This was in a large trial (TB-2) and this represents the totality of the dataset; so there is significant statistical plausibility tot he claim. A similar result was seen in the Aducanumab patients as well as the Lecanemab patients.
J11
Contributor
Contributor
Posts: 3357
Joined: Sat May 17, 2014 4:04 pm

Re: Alzheimer's Disease Cured ! J11 Exclusive!

Post by J11 »

TheresaB, thank you for replying.

TheresaB, I appreciate the emotional significance of the word cure. In many illness cure has seemed an endless mirage across centuries-- the word can take on the connotation of something that is unattainable. Surprisingly, as we have seen, this has not been true with AD. There has been a near continuous movement upfield for mabs starting with Aducanumab and with the recent announcement of the medium term of preventative dosing for Lecanemab this will only continue. The basic idea here is that once you have a treatment effect and there is no resistance (e.g., with bacteria) large patient benefits become possible. This seems especially true when there is a central disease driver such as amyloid.

In our family experience, the latest development of 95% slowing in the early MCI stage would have amounted to a functional cure over the many years that we struggled with it. We waited and waited and there was simply never anything that arrived that helped. A very large treatment window has now opened and those who have fairly mild features of the illness could actually proactively manage their mental well-being. There was a pre-dementia stage ( perhaps described as SCI) that lasted for years and years and was highly prominent and this would have been a great time to treat with a mab. 95% slowing would have prevented so much of the later decline possibly including the mild AD, then the moderate AD and then the Severe AD. If we had been able to hold the line at 20 MMSE, I am not ensure whether we would even have considered it as AD at all but basically just life. 95% slowing? It is very hard not to call that a cure from our perspective; we might then have had a somewhat normal life.

I am not sure how this is misleading; this is not a flamboyant claim without scientific backing -- it was reported at CTAD and has been confirmed in various other reports for Aducanumab and for Lecanemab. I think what is highly misleading is the mainstream depiction of the mab results. Simply saying that AD patients had on average 27% or 36% slowing does not truly reflect the fact that a subgroup of these patients had a 95% slowing (admittedly perhaps not prospectively described and this is only a modeled outcome with likely smallish n in the top responding group).

I really do not see this as undue or false hope. This result was presented at CTAD. Denying facts amounts to little more than deliberate obfuscation. Considering that AD patients can have substantial cognitive impairment, such obfuscation can be even more harmful to them.
J11
Contributor
Contributor
Posts: 3357
Joined: Sat May 17, 2014 4:04 pm

Re: Alzheimer's Disease Cured ! J11 Exclusive!

Post by J11 »

JulieG, it is difficult for me not to celebrate 95% slowing as an equivalent to a cure. In terms of what 95% slowing would have meant to us-- yes, that is a cure. All of the progression that we lived through would not have happened. 95% slowing means that we would have had only 1 year of progression over 20 years (instead of 20 years). That is simply staggering! If we could have even claimed 5 years of that slowing it would have dramatically changed the illness course. It would have meant that years of 24/7 care would not have been needed. There were years of fairly intense medical supervision. If we had been able to claim 10 years then legal competency would never have been lost and semi-autonomous activity could have been retained. From our life perspective 95% slowing would have had overwhelming clinical significance to us. It is very difficult to understand why others are saying: "J11, how could you say that that is a cure?" "How could I say that it wasn't?" This is much more benefit than we would have needed to have lived a mostly normal life. This life transformation is now approaching for the 315 million pre-clinical AD patients that are in exactly the same position that we were in, though they will be able to stop the progression before it continues and continues and continues. It is difficult for me to accept 2023 as the Year of the Obesity Cure when the lives of so many hundreds of millions of people will be so much improved by mabs.

I do recognize that potential harms exist with mabs, though even this is now in rapid evolution. In the pre-onset condition (i.e., in a preventative treatment model) greatly reduced dosing becomes possible. The current treatment approach is to try and remove ~70 centiloids of amyloid over 18 months. As we relax this constraint we could go to removing ~30 centiloids over 5 years or 10 centiloids over 10 years. We have already seen how ARIA rates are directly tied to mab dosing. There is of course a duality between efficacy and safety; some might want greater safety with lesser efficacy. With the 95% slowing reported, such a tradeoff becomes even more doable. We are all too aware of the complications that can arise with untreated amyloid in e44s (especially CAA). Doing nothing with CAA and other
risk is not a neutral choice. mabs would be expected to largely eliminate the risks associated with brain amyloid; so, once cleared mab treated patients would be expected to have lower safety concerns. With preventative treatment the potential emerges for patients to have better efficacy and better safety than placebo.

We are seeing very strong advance in the mabs and expected patient outcomes are improving. Into 2024 we are expecting yet more progress in which perhaps combinations will further amplify the success of the mabs in efficacy and safety terms. There has been such fantastic news and more is on the way all the time.

Best Wishes for the holidays JulieG!
The best has yet to arrive!
2024 already looks like it will load up my Celebration schedule!
Too many Celebrations-- too little time.
User avatar
Julie G
Mod
Mod
Posts: 9205
Joined: Sat Oct 26, 2013 6:36 pm

Re: Alzheimer's Disease Cured ! J11 Exclusive!

Post by Julie G »

JulieG, it is difficult for me not to celebrate 95% slowing as an equivalent to a cure. In terms of what 95% slowing would have meant to us-- yes, that is a cure. All of the progression that we lived through would not have happened. 95% slowing means that we would have had only 1 year of progression over 20 years (instead of 20 years). That is simply staggering! If we could have even claimed 5 years of that slowing it would have dramatically changed the illness course. It would have meant that years of 24/7 care would not have been needed. There were years of fairly intense medical supervision. If we had been able to claim 10 years then legal competency would never have been lost and semi-autonomous activity could have been retained. From our life perspective 95% slowing would have had overwhelming clinical significance to us.
To cure a disease, means that it is gone after a single treatment, then ultimately eradicated from the world. Very few diseases (less than a dozen) have been "cured" in our lifetime. And several on that list, such as measles, keep reappearing. Alzheimer's disease has NOT been cured as much as we all wish that were true.

J11, it is tempting to imagine a world in which your mother may have been offered this drug very early on in the disease process and avoided all of the pain she and your family endured. But, it's important to keep in mind that many of us are still in the trenches and this latest result does NOT present a cure for our loved ones. It is one estimate from a statistical model based on a clinical scale trajectory that has NOT been proven. (I invite the community to review the presentation.)

Additionally, we don't know that the actual results aren't the result of a practice effect on the cognitive testing, which is especially prevalent in an MCI population. (See here.) We also also don't know how the accompanying loss of brain volumetrics will affect these participants down the road. One thing we do know is that the "mabs" are less effective and more dangerous for ApoE4 carriers.

Please stop spreading misinformation. It violates every provision —Curiosity, Respect, Humility, Kindness & Trust— in our Community Guidelines.
Post Reply