The End of Alzheimer's

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J11
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The End of Alzheimer's

Post by J11 »

With all of the emerging powerful AD treatment rapidly approaching it has me thinking about what happens after AD has been conquered.

This motivated me to look at the long term figures for the leading causes of mortality. The three figures below capture most of the leading causes of mortality over the last ~70 years. The bottom figure shows the Big 3: Heart Disease -- Cancer -- Stroke. The middle figure shows some of the middle ~5 "pathological diseases". The top figure shows more the behavioral (Diseases of Desperation) and neurological (AD) leading causes.

It is disappointing in the figures below that certain "modern illnesses" were only all of a sudden recognized as
diseases. For example, AD was only noticed as a disease for reporting purposes in ~2000?
No one had even perceived there was a dementia crisis until then? Similar to what we saw with COPD.
No one realized that there was a respiratory health crisis (largely from smoking) until ~1980?

To avoid such absurdies it would probably be best to give more prominence to a multiple cause of mortality interpretation. While AD might often not be the precise "cause" of mortality in many instances, it would nonetheless be a contextual factor of substantial importance. I think including such broader context to move beyond often statistics devoid of actual human meaning would be of great use in revealing the medical circumstances that people faced. It seems to me to be ludicrous to possibly point to all sorts of peripheral features that might be present with AD mortality for example, bed sores, etc. etc. and somehow see these as causal when clearly AD itself will be the underlying driving features that is dominating the life choices of the person involved. In such a conception of reporting, the true AD presence could be extremely high.

Regarding digital storage. Seriously, we now have a near infinity of digital storage capacity; there is no longer need to worry about all the trees that will need to be clear cut to print out all of the information. Perhaps each person should be allocated 1 megabyte of digital memory to statistically encapsulate their life experience; for medical and other edification.

It would help to inform where research dollars should be directed. Otherwise, you wind up with the discovery of AD in 2000 even though from a multiple causation perspective this would have been obvious for decades. Even now AD is likely highly under-reported in the leading causes as it can be clinically present, though might be largely ignored.

It is also disappointing that there are no examples shown in which a leading cause simply disappears all of a sudden.
One might suspect that with a miracle type breakthrough that would be possible. You find a pill and tomorrow Disease X no longer exists. During the last century this does not seem to have happened. The figures below show more of a 2% decline ... another 2 % decline ..... and then over the space of 30-50 years an illness gradually recedes (for example, heart disease or stroke).

Yet, for Alzheimer's my suspicion is that we will see a dramatic decline in the rate starting possibly within ~1 year. This would be a first. Being able to halt progression (or nearly so ~90% with LMTM) as has been demonstrated should dramatically and rapidly bring AD under control. If progression could be stopped even into the moderate stage, then AD would no longer be a mortality driver. We noticed that even with profound disability the actual impact on health was not that large. Roughly, a 90% decline in the age adjusted rate within 10 years of a first effective AD medication (e.g., LMTM) seems plausible to me. Such a massive rapid decline in a top cause over the last century (in a non-infectious illness) has never occurred before.

This is a very exciting conjecture. As soon as the reports of greatly reduced progression of AD are confirmed (possibly within the next 2 months) we could then project forward to a time in the medium term where AD is no longer amongst the leading causes of mortality and possibly could have almost vanished.


Leading 3a.PNG
Leading 2a.PNG
Leading 1a.PNG
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Last edited by J11 on Thu Jun 23, 2022 9:11 pm, edited 5 times in total.
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Re: The End of Alzheimer's

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Just to be clear about what I suspect might happen with the AD rate over the next 10 years, we could see something similar to the figure below. It would not be overly surprising if it were even more rapid than a simple linear decline. It might not take a decade to reach super-low AD rates.

Stopping progression even at the earlier stages could rapidly halt mortality. For us stopping progression at MMSEs of 27 ... 24 ... 21 ... 18 ( legal competency) ... 15 ... 12 ... 9 ... 5 ... 3 (possibly even somewhat lower) would have stopped the link to mortality. When AD patients are immoblized in bed for years there can be a few problems that arise ... for example, spasticity, orders of magnitude more personal care, possibly seizures ( seizures only arose for us at the immobile stage), also physically having to roll them for personal care, etc..

Of course, moderate dementia also presents significant challenges, though this is more related to managing ambulatory dementing behaviors more so than mortality directly. From our perspective, stopping progression anytime before full bed immobilization would remove AD as a mortality risk. It is not as clear how the new treatments would impact those with the later stage of progression. If ADL could gradually be restored from total immbolization that would be fantastic. It would mean that AD could become completely uncoupled with mortality.


There is no precedent in at least the last century for a chronic illness to fall and perhaps vanish in the way suggested.
Perhaps one wiggle for this is that it might be found that there is not a monolithic Alzheimer's as is now presumed.
For pure APOE epsilon 4 Alzheimer's (~50% of total AD) it appears to be green lights for as far as you can see . Yet, for other forms of AD (e.g., non e4 AD) it might take more time to develop effective treatments; it might also be decided that these patients do not even have classical AD at all.

The suggested pattern of an abrupt collapse in related mortality in AD with the arrival of effective treatment might apply to other brain proteinopathies such as Parkinson's, ALS etc.. These patients can be quite healthy aside from the brain proteins and they could be largely good to go with treatment. This is in sharp contrast to the other Diseases of Desperation in the figure. It is actually remarkable and highly disturbing to see this near exponential ramp up in drug overdoses that has occurred over the last few decades. Solving these problems could be much more difficult and likely will not be as simple as a prescription for a pill.


US Alzheimer 1950 2018 Extrap.png
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Re: The End of Alzheimer's

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I have been reading up on autonomous vehicle navigation technology. Interestingly, it appears that perhaps over the medium term that motor vehicle mortality could be one of the few leading causes (aside from AD) that might almost disappear. If we were to let a supercomputer drive our cars, then there would probably be a great fewer accidents. It occurred to me also that if we were to let an artificial intelligence agent do our shopping for us then it would probably also have a dramatic effect on human health. People are the problem! Let people make their own choices and see what happens!
Last edited by J11 on Sat Jul 09, 2022 11:43 am, edited 1 time in total.
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Re: The End of Alzheimer's

Post by floramaria »

:lol:
J11 wrote: Sun Jun 26, 2022 6:36 pm It occurred to me also that if we were to let an artificial intelligence agent do our shopping for us then it would probably also have a dramatic effect on human health. People are the problem! Let people make their own choices and see what happens!
I'm not letting AI shop for me! :lol:
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J11
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Re: The End of Alzheimer's

Post by J11 »

Flora, it's brilliant!

The supercomputer can figure out everything for everyone!
Why, it will be truly panglossian-- the best of all possible worlds!
I suppose getting us out of dementia prison will allow us to make some improvements
that the non-dementeds might never have thought of (or thought of and decided it best
to keep it to themselves).

When you leave things up to humans: Look what happens!
If AI can solve motor vehicle accidents, why not solve everything as well with AI?
With a grocery shopping cart under AI control and ethernet linkage to the family
weighing device, I suppose the global obesity pandemic could be solved rapidly!
Goal!

It could be sort of like a religion.
Everything would be all setup for you; all you would need to do is show up and you're set.

Just think, we could prove to everyone that everything is the best it could possibly be for everyone.
How could they complain when life is optimal?
Everyone would be optimally healthy (probably an extra dose of oatmeal will do everyone some good) ...

Hmm.. yes I suppose even in the best of all possible worlds there would still be complainers!
Some people just would not be happy if they weren't complaining.
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