#1

I often feel that as aggressive longevity and health extension people, dementia/AD (and cancer) are less under our control than metabolic, cardiovascular and other vital organ related diseases and hence found some of the perspectives in this new Newsweek piece interesting

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When Aisen started, Alzheimer’s disease was thought to begin with the onset of observable cognitive and functional decline and, after progressing for seven years or so, result in death. But the onset of early dementia, we now know, is in fact just the final phase in a far longer progression that takes place over roughly 25 years. It begins with the accumulation of amyloid-beta at least 18 years before any behavioral changes are detectable to most future patients or their loved ones.

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“For all of history, people have been afflicted by senility and dementia, and for thousands of years, you couldn’t do anything about it,” says Bateman. “Even in recent history, you could only diagnose people after they died. Now a single blood sample can with 95 percent accuracy identify Alzheimer’s. And in just six to 18 months, we can remove plaques from the brain that have built up over 20 years. We can for the first time change the course of how fast the disease progresses. To me, it’s just absolutely incredible. It’s really profound.”

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Reiman, in fact, believes these side effects might be less of an issue for those in an earlier phase of the disease. In the late stages, he says, “you’re having to pull amyloid plaque out of the brain, but also off of blood vessels, which is the main reason for the side effects,” such as bleeding and swelling, he says. In the brains of those who are at earlier stages of the disease, the plaques “haven’t been there as long. So, they’re less adherent, and you may have fewer side effects as well.”

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Interesting perspectives here on how very early action via the new FDA drug(s) (and others in the pipeline) could
(a) perhaps have a big impact on preventing AD and
(b) perhaps also have a much better safety profile in those early stages such that early intervention might make sense

The next 5-10 years may be quite exciting and interesting here:

In the hopes of further arresting this systemic collapse, Aisen is co-leading the AHEAD trial, which is in the midst of recruiting “presymptomatic” patients to participate in a four-year study of lecanemab. The new cohort will consist entirely of people who are, for the most part, cognitively and functionally asymptomatic but have abnormal levels of amyloid in their brains. The idea is to capture people in years one through 10 of the progression. A later phase of the trial, he says, will target a cohort who is “even closer to year one.”

At the same time, the TRAILBLAZER study, co-led by Banner Institute’s Reiman, is taking a similar approach, but using donanemab, the new drug from Eli Lilly that is expected soon to win FDA approval, to target those in earlier stages of the disease.

It will take five years before AHEAD yields results, estimates Aisen, and 10 years before we have a real handle on how to prevent the disease. Reiman is slightly more optimistic but agrees many more steps are needed.

Still, both see a bright future ahead.

“Lecanemab is a real landmark. Having a fully approved drug [that] slows the disease is significant. But we’ve got to move on and increase the benefit,” Aisen says. “I’m very optimistic. We’re just going to build on this success. Things will get better and better until the entire population is routinely screened for risk and the risk is fixed before the disease starts.”

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#2

  1. More support for the thesis above that early treatment is more effective

  2. (home) injectable might as good or better than more cumbersome infusions; might have (non statically) higher risk AND more effect, but as discussed above these risks may be massively lower in early prevention vs later in the course:

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Analysis of Lilly and Eisai’s Alzheimer’s trials suggests early treatment has greater benefit – Endpoints News

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#3

Some researchers believe infections are a primary cause. Bacteria, yeast, viral. The article below reports on a new study linking candida to Alzheimer’s. Another review below discusses the possibility of bacterial infection being a cause. Doxycycline is an antibiotic that has the ability to both penetrate bacterial biofilms and cross the BBB. It has about a 24% penetration rate (100 mg x 4 = 400 mg daily). Fluconazole is reputed to be the safest antifungal medication, and also has the ability to cross the BBB. Doxycycline significantly potentiates the effects of fluconazole against candida, which may make it an effective combo.

Nitazoxanide has broad antiviral activity, also effective against a range of parasites and some bacteria. It is a benign medication with a good safety profile. It can cross the BBB, and has been shown to improve symptoms in AD model mice. It also promoted clearance of Aβ plaque. It also has mitochondrial uncoupling and autophagy enhancing properties. It also prevented atherosclerosis in mice fed a Western diet in a study. A possible antiaging compound. It also has significant anticancer activity. And there is preliminary evidence in animals that it may be an effective cholesterol lowering medication.

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Predicting Alzheimers & Dementia (and minimizing risk)
#4

Broad-spectrum antiviral agents (BSAAs) and viruses they inhibit

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#5

Thanks for this synthesis @Vlasko

Any sense of optimal protocols - how long treatments and how often to come back and dose?

I’m especially concerned about impact on our microbiomes - what are your thoughts on that? Any ways we can minimize the impact while still getting the positive effects if the antibiotics?

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#6

FWIW

You are aware that doxcycline is available in an injectional form for IV or IM. Avoiding the intestine track.

You can measure doxcycline levels in blood, Quest is one lab that can preforms this test.

In my view, FWIW people create too much BS about doxcycline. I have been taking 100mg every 8 hours since September 25th, 2023 without any issues.

As some members of this forum do not care for my reply on this subject.

Shamelessly Plagiarism

"Those that say in can not be done take a backseat to the people doing it”

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#7

Thanks for this. Does that mean that there is no systemic effect back onto the gut microbiome?

Do you target anything specific level?

#8

Look up the package insert for the injection version.

The test by Quest is test code 90493, review the information:

https://testdirectory.questdiagnostics.com/test/test-detail/94093/doxycyline?cc=MASTER

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#9

What are people’s thoughts - could be huge? Eventually we all get apoe2…?

IMG_6396
IMG_63961179×2556 233 KB

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#10

Still, another methylene blue video by an MD.
Some interesting thoughts on the use of methylene blue for Alzheimer’s prevention and possible reversal. Also, the doctor uses it himself and claims it reduces brain fog.

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#11

I use methylene blue and find it is helpful under times of very high need for brain activity.

I think the problem is, once disease is well established - it is very difficult to do anything that helps. Preempting it is my strategy, and only time will tell if it works.

I have a lot of patients on MB, and there is a good source available with 12 mg capsules so you don’t stain your teeth. If you are of Mediterranean descent, might check for a G6PD before taking this, although in the dosing <0.5 mg/kg/day I don’t think we’ve seen issues with this, and certainly the doses are less than this.

Vera-Health.ai, on this topic says:
Methylene blue (MB) has been investigated for its potential benefits in Alzheimer’s disease (AD), primarily due to its ability to inhibit tau protein aggregation, a key feature of AD pathology. MB’s mechanism involves reducing tau aggregation, enhancing mitochondrial function, and decreasing oxidative stress, which are critical factors in AD 23.

Despite these promising mechanisms, clinical trials have yielded mixed results. A recent Phase III trial did not show significant benefits, possibly due to MB’s limited action on tau fibril formation rather than the granular tau oligomers crucial for neuronal death 2. However, smaller doses of MB have shown potential in slowing cognitive decline when used as monotherapy 6.

Efforts to improve MB’s efficacy include developing advanced delivery systems, such as nanoscale drug carriers, which have shown promise in preclinical studies by enhancing MB’s bioavailability and targeting capabilities 7. Additionally, MB has demonstrated synergistic effects when combined with other therapeutic agents, such as 4-phenylbutyric acid, which may protect neurons from amyloid-beta-induced toxicity 4.

In summary, while methylene blue exhibits several mechanisms that could be beneficial in treating Alzheimer’s disease, including tau aggregation inhibition, mitochondrial enhancement, and oxidative stress reduction, its clinical efficacy remains uncertain. Continued research, particularly in optimizing delivery methods and understanding dosage effects, is necessary to fully elucidate MB’s potential in AD therapy.

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#12

Thank you for this informative post. Would so appreciate it if you could point to the source for the 12 mg capsules. Also, what are your decision criteria for putting your patients on MB?

#13

Here are my generic instructions I have for Methylene Blue for my patients - not to give anyone individual advice, but for suitable patients, here is what I provide:
Methylene Blue
First, make sure you not on any SSRI or MAO-I antidepressants. Second, with low dose Methylene Blue, it is unlikely, even if you have a G6PD Deficiency that you would not get into trouble – but this compound can cause your red blood cells to “hemolyze” or break down, which can be serious. Especially if you are of Mediterranean or African descent, get this tested (blood test) before starting Methylene Blue. Interesting videos to watch below:

A trial of Methylene Blue is primarily guided by whether this adds mental clarity and decreases fatigue – if so, continue.

Dosing:
Generally start with 8-12 mg each morning (which is often a sufficient daily dose for many people), after 1 week if doing well, and if you have a sense of energy not being optimal later in the day, you can choose to add a second dose around lunch (generally 5-6 hours after your morning dose, but not close to going to bed). If you work out first thing in the morning, generally wait to take this until right after your workout.

Select from:
Nutricel Blue Boost 12 mg. Amazon.com
The advantage of this, is it is encapsulated, so no blue tongue/teeth, but a fixed dose of 12 mg.
Tro Just Blue. Just Blue – Troscriptions Code: FRASER gets your 10% off
The advantage of this is a wafer that can be broken into 4 mg doses. The downside is 4 wafers (16 x 4 mg dose) on subscribe and save ends up being $23 for not very many mg. These can be swallowed or dissolved in the mouth, but allow for smaller doses or adjustments. If starting with these, can start as low as a 4 mg, and gradually go up.

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#14

If infections are the primary cause of AD, then why do twins who grow up in different environments have a similar rate of AD? How does this fit in with early onset AD, and ApoE4/4. Allegedly ApoE4/4 developed precisely to better fight brain infections, and that is why the carriers had an evolutionary advantage in a high pathogen environment, yet it is them that get AD at a higher rate. The more of the 4 they carry, the worse off they are. Meanwhile ApoE4/4 carriers in Nigeria don’t experience higher rates of AD, but have very different diets than Westerners. Are there less infections in Africa, lol? ApoE2/2 carriers are drastically less prone to AD - are they less prone to infections? Do early onset AD people have especially many infections that carry on over generations in the same families? Why do some genetic markers increase the chances for AD? Do those markers make them more vulnerable to infections? AD sufferes have much lower rates of cancer - do infections prevent cancer?

Infections causing AD, is a hypothesis, like any hypothesis it must be tested and counter evidence considered. That doesn’t mean that it’s not possible for some cases of AD to be down to it, after all some viruses do cause cancer, but viruses are not the primary cause of cancer. Similarly, the hypothesis that infections are a primary cause of AD seems to me a bit loopy, BWDIK.

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