Predicting Alzheimers

And here is a follow up in the series. The whole documentary is out soon, so those who prefer TV version can also take a look at that.

Quite amazing how basically medically guided “biohacking” targeted at being proactive and triangulated with a lot of biomarkers can have this effect.

Will be very interesting to see the clinical trial data when complete.

Some snippets here I found interesting and relate to issues we have been discussing on the forum - including the value of doing the blood based biomarkers for AD and dementia risks:

As part of the trial, Nicholls underwent a battery of tests, including a unique blood test that can track levels of amyloid, tau and other hallmark biomarkers for Alzheimer’s disease and other degenerative conditions. Deposits of amyloid can begin accumulating in the brain decades before symptoms begin, even in a person’s 30s and 40s.

In August 2023, it was time to repeat the blood test for amyloid. By then, the company that administers the tests had added a measurement for tau, another key hallmark sign of Alzheimer’s, frontal lobe dementia and Lewy body disease.

Within six months, Nicholls had dropped the levels of amyloid in his blood from 70 to 53.

On Halloween 2023, the next APS2 score arrived. Amazingly, Nicholls had reduced the amount of amyloid and tau in his blood to 40: He was testing negative in blood for signs of Alzheimer’s.

Shocked and amazed, Isaacson remained skeptical. “I was very cautious. You know, promise not to overpromise. I needed to retest.”

A few days before Christmas, the repeat test results arrived. When it too was a negative finding of 40, Isaacson decided to tell Nicholls in person.

Even lower amyloid levels and a larger hippocampus

It appears Nicholls is well on his way toward that goal. In March, his APS2 score had dropped to 25, an unbelievably low number.

Even more startling: Brain volume scans showed that the hippocampus, the tiny seahorse-shaped organ responsible for memory, had actually grown in volume in Nicholls’ brain since he started the intervention.

In early Alzheimer’s stages, the hippocampus loses tissue rapidly and then atrophies as the disease progresses.

Despite these amazing outcomes, Isaacson remains cautious. After all, this is one person, and similar findings have not been been replicated in a larger, more controlled sample and published in a peer-reviewed journal.

That doesn’t stop his wonder at the results and his gratitude to Nicholls for his continuing dedication to the study and the personalized interventions.

“I still can’t believe it. I’d seen this before, but only in people who are taking anti-amyloid medications,” Isaacson said. “When you work your entire career and are told by everyone, ‘It’s not possible to do this,’ and then you see it — well, I’m still humbled and amazed.”

Elevated homocysteine, which is an amino acid used by the body to make protein, is a risk factor for brain atrophy, cognitive impairment and dementia. A September 2010 randomized controlled trial found that supplementation slowed brain atrophy in people with mild cognitive impairment.

Consider joining Isaacson’s latest online clinical trial, designed to provide cognitive assessments and personalized advice via smartphones. People over 21 who meet certain criteria can sign up for the study at Retain Your Brain.

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I liked the image provided in the report. It shows you the supplements, diet and other interventions that proved useful in preventing AD.

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Dr. Richard Isaacson is really good. His recent paper (already posted in another topic) on preventive neurology presents the state of the art on the field: Alzheimer’s disease risk reduction in clinical practice: a priority in the emerging field of preventive neurology | Nature Mental Health

I’d like to see an update of the paper mentioning SGLT2i, telmisartan (but ARBs are already mentioned), low-dose lithium, ezetimibe and obicetrapib, and TMS/tDCS/red light therapy.

I guess Isaacson was more conservative in this paper. Do we have the whole list of interventions (both pharmaceutical and non pharmaceutical) he recommends to his patients?

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I developed Hallux rigidus, or stiff big toe in both feet. My own opinion is that came from being in western narrow toe shoes while running. I went to a podiatrist and PTs - either a surgery to fuse the joint or try running shoes like Hokas. On my own I sort of figured out the toe spacer remedy. Our bones are pretty malleable (think braces as an example). It works. Slept with the spacers overnight and also used while in wide forefoot shoes. Pretty good range of motion now in the big toe which is really important for being able to jump and balance. Highly recommend it. (Side note: never underestimate the things in our environment that are causation for certain morbidity - a pox on western shoes!)

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Yeah, would be great to have - perhaps we can see some of it in the documentary. There is some of that in the two CNN articles and perhaps there will be more of those.

Btw - interesting to note that he does seems to focus on Hcy. Including the MTHFR genes (see @DeStrider post above) - has anyone looked into those mutations?

Thanks for sharing this experience

Which specific options/brands would suggest one looks into?

and also used while in wide forefoot shoes. Pretty good range of motion now in the big toe which

Btw, what are these - some special type of shoes?

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I used something like the following. See Amazon But any variation would work given one’s preferences. Find various sizes to fit all the spaces. Go cheap. It feels oddly relaxing just spreading the toes - who knew :slight_smile:

Altra is probably one of the better known brands for a wide forefoot. They also design the shoe for “zero-drop” which just means no heel raise like normal western shoes. So a little less force on the forefoot and theoretically a more natural gate for walking and running. That can also cause people to strain their achilles which is not used to the strain with “normal” western raised heel shoes. So start slow if trying.

A lot of other companies are offering a wide forefoot. Even Nikes - notorious for a narrow forefoot is offering wide forefoot options.

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I looked a bit at MTHFR mutations (as I have one of those causing high Hcy). From what I understand they’re like high Hcy: a risk factor for many cardiovascular, neurological and psychological diseases. So people with these should probably be even more cautious about high BP, high BPV, sleep, stress management, diabetes, ApoB, etc. And they should also check their B6, B9, and B12 levels and if not “optimal” (TBD…) supplement with the “methyl” form of these vitamins. What is unclear yet to me is whether people with high Hcy but optimal B6, B9, and B12 would benefit from supplementation with these vitamins. I would assume than not (based on the MR studies and trials I posted in the other topic) and that for these people there might be other causes of the high Hcy that need to be addressed via other pathways (which ones? :man_shrugging:).

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Homocysteine is an interesting one - I routinely check it and normalize it. I have some patients that likely have an issue with transport of folate into their cells - whether a defective transport mechanism or antibody to the receptor.
For these folks, and my wife is one of them, Folate is >upper limit of normal, and Homocysteine is still high. It will usually get normalized with Folinic Acid. She had folate>24 and Homocysteine of near 30 - with folinic acid now in the 8’s.
For Hcy, easy to remember, is rule of 3’s, B3,B6,B9,B12 all impact it - if Folate is high, go with folinic acid and this usually works as the activated methyltetrahydrofolate simply is probably not getting into the cell.
For folks without a high folate level, I like the life extension BioActive Complete B complex as it is cheap and a really decent product.

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Effects of intensive lifestyle changes on the progression of mild cognitive impairment or early dementia due to Alzheimer’s disease: a randomized, controlled clinical trial

Full PDF (Open Access) for download here: https://res.cloudinary.com/ornish/image/upload/v1717741018/Lifestyle_Changes_and_Alzheimer_s_study_64f59728fb.pdf

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