Predicting Alzheimers

Alzheimers is #1 in my priority of worries. At present, age 74, I have no issues or warning signs. But my mother, aunt and grandmother, all very long lived, have/had it. I am well and fit, but A1C has been 5.7-5.8 for many years with no progression. Taking Metformin. I just ordered some Rapamycin.

Aware that if take it before there are amyloid placques, Rapa can be protective. But if taken after amyloid placques / tau start to form, Rapa can actually hasten decline. It has to do with whether the lisosome is still functioning optimally and is clearing out the junky proteins. Once the lisosome starts to malfunction, it is too late to benefit from Rapa; in fact at this stage Rapa is likely harmful.

There is now a test offered by Quest called AD-Detect. It can be ordered by the consumer but is not available in NY, where I live. Anyone here know about it or have taken this test?

Any guidance re: whether it is OK for me to start Rapa at my age, healthy but with family history? Would welcome input on this –

https://testdirectory.questdiagnostics.com/test/test-guides/TS_AD_Detect_BetaRatioPlasma/quest-ad-detect

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Do you have references for the impact of Rapamycin in Alzheimer’s? I hadn’t read this before. I should clarify, in humans.

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Rapamycin can increase apoB which preliminary data shows is causally related to Alzheimer’s disease. If your apoB is and stays low (preferably with normal serum desmosterol, cholesterol lowering treatments could suppress synthesis too much), then it could be fine. Low apoB is important for CVD either way.

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My Mother lost her younger sister to Alzheimers. My mother began having noticable short term memory loss. 2.5 years ago we started her on Rapa therapy. I can’t say we have a cure. N=1, dramatic improvement though.

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So she started Rapa after symptom onset?

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Yes, a little after turning 78. Her STM had been a famial point of concern for a few years before, mild but present. Her sister died at 75 after 3.5 years of really heartbreaking A-D progression.

This conclusion was based from one mice study I believe. On other hand there many more studies purporting improvement in cognition in mice.

Matt Kaeberlein says it best here:

It is possible that rapamycin might only be effective at delaying AD if treatment is started before the disease has progressed to the point of clinical diagnosis. However, at least a subset of preclinical studies reported positive effects of rapamycin in mouse models even after substantial AD-like cognitive deficits and histopathology were present (17, 20). These observations, combined with the ability of rapamycin to improve function in other tissues, most notably the cardiac and immune systems (29, 32, 38–41), raise the possibility that cognitive function could be improved in patients with early- or moderate-stage AD even after substantial cognitive decline. Optimally, we would recommend clinical trials for rapamycin efficacy both in patients with MCI who are likely to progress to a diagnosis of AD and in patients recently diagnosed with AD.

In fact the current human trial did jus that, pick candidates with MCI and early dementia for the rapamycin study.

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Hello Deborah,
Have you checked of your ApoE4 allele status? People with one or both are at an increased risk for AD.

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Thanks for your responses. The paper that talks about the potential harms of RAPA after onset of AD is: “Rapamycin and Alzheimers Disease: A Double-Edged Sword?” published 5/22/2019 in Autophagy.

If you read it I would appreciate your assessment –

I am encouraged by your inputs that Rapa has actually helped after onset of disease.

No, I do not have the APOE4 phenotype – I am APOE3. My main concern is actually that I will live long but be demented, as my mother (age 97 today) is now, even though my health and behaviors are very different from hers.

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@Deborah_Hall I took a look at the literature. Seems like you won’t get a clear answer because there just isn’t one yet. Human studies ongoing.

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Yes. See our thread here: Rapamycin and Alzheimer disease: a double-edged sword?

Other discussion threads related to Alzheimer’s and rapamycin:

  1. Rapamycin and Alzheimer Disease: a Hypothesis for the Effective use of Rapamycin

  2. Fighting Alzheimer’s with Increased Autophagy via Rapamycin + Trehalose

  3. UT Health San Antonio gains $2M to study rapamycin for Alzheimer’s

  4. New Study: Rapamycin protects against Alzheimers in Mouse Model

  5. Intranasal Rapamycin Lessens Alzheimer-like Cognitive Decline in a Mouse Model of Down Syndrome

  6. Rapamycin increases Alzheimer's-associated plaques in mice, study finds

  7. A drug cocktail of rapamycin, acarbose, and phenylbutyrate enhances resilience to features of early-stage Alzheimer's disease in aging mice

  8. Rapamycin restores peripheral blood flow in aged mice and in mouse models of atherosclerosis and Alzheimer's

  9. Rapamycin and AD

  10. Mitophagy Activation by Rapamycin Enhances Mitochondrial Function and Cognition (New Study)

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I would try this https://pendulumlife.com/products/pendulum-glucose-control-2-og

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Definitely want to get the blood glucose under control: Diabetes, air pollution and alcohol consumption could be the biggest risk factors for dementia

And, it seems research may support the idea that you want to get the blood glucose well under control before you start rapamycin: People With These Health Conditions Should Not Take Rapamycin?

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Indeed - Type 3 Diabetes - is essentially what many of us think is a substantial cause of late dementia. This is a different situation, potentially, than early dementia, which is multi-factorial, including ApoE4 positivity.
Insulin resistance and lack of proper utilization of glucose in the brain is likely a cause of some of the pathological changes in the brain with late Alzheimer’s Dementia.
I suspect this is why, diabetic drugs are having such strong signals as medications to decrease cognitive decline and probably also Parkinson’s Disease.
Other factors including solid use of the brain, include optimizing Omega 3 index, tight blood glucose/pressure control, management of stress/sleep/social connections, adequate whole food plant based diet for photochemicals/gut health, and adequate exercise.
It’s a big package to implement - and rapamycin is certainly part of the mix here - but it’s only part of a bigger lifestyle to obtain better health outcomes.
Those of us in the longevity medicine space advise our patients that only 15% of health outcome is genetics — 85% is life choices. This is a double edged sword, as so many people look at their elders and think that their parents living to 95 is relevant. Their exposures, diet and activity are often dramatically different. On the other side, people who have parents with huge comorbidities and death earlier in life - should be encouraged, in general - if their parents made very poor lifestyle choices (smoking, lack of proper management of medical conditions, sedentary, obese, etc) - that it is not going to be their health outcome if they manage their conditions and co-morbidities.

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Are you aware of any independent data supporting this product?

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Both from experience and from research available at PubMed, I strongly (that really should be all caps) recommend looking into taurine. In animals, it prevents or halts neurodegenerative diseases including Alzheimer’s and Parkinson’s. Last I looked, there were promising results in early human trials.

Experience: Two years ago, when I was 73, I began taking 2000 mg a day of taurine. Two days later, waking up was like waking up to a whole new reality. For some time, I had been forced to enter the first three digits of a six-digit security code and then look at the second half again. That problem was gone. Two weeks after that, I needed a 15-digit part number, read it twice, and still remembered it weeks later.

I also recovered cognitive abilities I had not been aware of losing. For some time, when faced with a minor difficulty in some minor chore, I had simply plodded on until it was done. Suddenly, I was automatically reaching for something nearby that would solve the problem–a paper, a bit of string, a spreading knife–whatever was handy and none of them used for their original purpose.

Owing to that research on lifespan a year or so ago, I now take 5500 mg per day at 160 lb weight. That is how the standard animal-to-human conversion came out. Adjust as required.

Strongly recommended.

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Thank you for this. Have been taking a low dose of Taurine but will increase and start my husband on it as well.

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Below is a new review on composition of drinking water and incidence of cognitive decline in the elderly. Alkaline water and silica may be protective. Silica may also reduce absorption of aluminum. Perhaps avoid acidic beverages like soda in favor of alkaline teas.

Both alkaline water and organic silicon may have general anti-aging benefits per animal studies as well. I take an orthosilicic acid supplement in my daily collagen drink. Promotes collagen synthesis, improves nail quality.

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No independent data yet, I don’t think. But some confirmation from people (anecdotal)… discussed here: Akkermansia mucciniphila improves healthspan and lifespan in old female mice - #3 by Pestodude

I work with Alzheimer’s patients, am one of the authors on the Precision Medicine Trial published 8/22. The biggest contributors to AD for ApoE3/3 women are insulin resistance and failure to replace hormones (bio-identically) @ menopause. Toxins also play a role, especially mold and Lyme. Lab Corp now has an even better test, ATN panel with measurements of amyloid beta, pTau, and Neuofilaments.

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