1230 replies to this topic

[mag1]

I am going to take a complete leap into the unknown on this one.

If you remove amyloid from plasma, then this could have an osmotic like action in flushing out other amyloid as it tries to equilibriate under the new amyloid depleted conditions.

 

This would seem to be a large step forward for Alzheimer's care.

These treatments are already available.

The clinical trial has been ongoing for 7 years, so they should have some idea how this treatment carries forward over the longer haul.

It would be very startling if a 60% reduction in decline could be maintained over a multi-year followup.

 

[Phoebus]

Here is another thought 

 

Why not use the plasmapherasis method to PREVENT Alzheimers in the first place? Why not put those at risk of Alz on the treatment, thus preventing it from ever taking off in the first place. 

[mag1]

The problem with Alzheimer's prevention is that it can be hard to know whether you have stopped something from happening: It just might not have happened anyways. To answer this question, clinical trials involving those with pre-AD need to be followed for years until progression to mild dementia occurs. Companies typically avoid such research as it can be quite expensive, while sometimes implying that early stage patients do benefit (even when this has not been proven) because the later stage patients benefited.

 

The cited plasmapheresis research did actually run into this problem. Statistically significant results for those with early dementia were not demonstrated. This is not overly surprising because the early stage patients on treatment along with those on placebo did not progress. It has been found that often early stage patients do not actually go on to to develop full AD and even when they do progress it can occur gradually. 

 

Considering the overwhelming cost of Alzheimer's, this might be a great opportunity for governments and/or others to step forward with some research dollars. Spending $100 million to determine whether this latest treatment might help those with early AD would be a shrewd investment seen from the macro-scale. AD is costing the global economy close to $2 billion per DAY. Can we actually afford not to invest this money? (Hint: Answer is NO). 

 

I probably should backtrack on my proposed mechanism of action. Lowering amyloid has up till this point not been found to be an effective anti-dementing tactic. In fact, amyloid levels tend to fall once neurodegeneration is underway. It is then entirely possible that something else is going on that is producing the therapeutic effect. With pharmaceuticals, it is typically true that the exact identity of what is going on is not known; the accepted mechanisms of action are often discovered after further investigation to have been incorrect. At this point, we should all be grateful that something does appear to help, even if the why it works question is somewhat obscure.   

 

Edited by mag1, 14 March 2019 - 03:40 PM.

[mag1]

Just in from the CDC: Alzheimer Epidemiology in the US.

This would surely suggest that people would tend to want a larger role of a government that provides protection against this unknown.

Plasmapheresis would tend to counter such a perspective as it offers a realistic path to self-managing this risk.  

 

https://www.cdc.gov/...sr68_02-508.pdf

Edited by mag1, 15 March 2019 - 01:45 AM.

[lancebr]

So, based upon this study would taking Ferulic acid and/or ECGC be of use for AD?

 

 

http://www.jbc.org/content/294/8/2714

[albedo]

Alzheimer's Blood Test Shows 94% Accuracy - Mass spectrometry assay and genetic screen predict brain amyloidosis

 

https://www.medpaget...rsdisease/81379

[mag1]

http://investors.bio...heimers-disease

[mag1]

Aducanumab- the first Alzheimer treatment to have shown disease modification in phase 3 trials and no one is interested?

[ta5]

Int J Environ Res Public Health. 2019 Dec 17;16(24). pii: E5152.

A Hypothesis and Evidence That Mercury May be an Etiological Factor in Alzheimer's Disease.

Siblerud R1, Mutter J2, Moore E3, Naumann J4, Walach H5.

Mercury is one of the most toxic elements and causes a multitude of health problems. It is ten times more toxic to neurons than lead. This study was created to determine if mercury could be causing Alzheimer's disease (AD) by cross referencing the effects of mercury with 70 factors associated with AD. The results found that all these factors could be attributed to mercury. The hallmark changes in AD include plaques, beta amyloid protein, neurofibrillary tangles, phosphorylated tau protein, and memory loss-all changes that can be caused by mercury. Neurotransmitters such as acetylcholine, serotonin, dopamine, glutamate, and norepinephrine are inhibited in patients with Alzheimer's disease, with the same inhibition occurring in mercury toxicity. Enzyme dysfunction in patients with Alzheimer's disease include BACE 1, gamma secretase, cyclooxygenase-2, cytochrome-c-oxidase, protein kinases, monoamine oxidase, nitric oxide synthetase, acetyl choline transferase, and caspases, all which can be explained by mercury toxicity. Immune and inflammatory responses seen in patients with Alzheimer's disease also occur when cells are exposed to mercury, including complement activation, cytokine expression, production of glial fibrillary acid protein antibodies and interleukin-1, transforming growth factor, beta 2 microglobulins, and phosphodiesterase 4 stimulation. Genetic factors in patients with Alzheimer's disease are also associated with mercury. Apolipoprotein E 4 allele increases the toxicity of mercury. Mercury can inhibit DNA synthesis in the hippocampus, and has been associated with genetic mutations of presenilin 1 and 2, found in AD. The abnormalities of minerals and vitamins, specifically aluminum, calcium, copper, iron, magnesium, selenium, zinc, and vitamins B1, B12, E, and C, that occur in patients with Alzheimer's disease, also occur in mercury toxicity. Aluminum has been found to increase mercury's toxicity. Likewise, similar biochemical factors in AD are affected by mercury, including changes in blood levels of homocysteine, arachidonic acid, DHEA sulfate, glutathione, hydrogen peroxide, glycosamine glycans, acetyl-L carnitine, melatonin, and HDL. Other factors seen in Alzheimer's disease, such as increased platelet activation, poor odor identification, hypertension, depression, increased incidences of herpes virus and chlamydia infections, also occur in mercury exposure. In addition, patients diagnosed with Alzheimer's disease exhibit higher levels of brain mercury, blood mercury, and tissue mercury in some studies. The greatest exogenous sources of brain mercury come from dental amalgams. Conclusion: This review of the literature strongly suggests that mercury can be a cause of Alzheimer's Disease.

PMID: 31861093

[ceridwen]

@mag1 I read somewhere that aducanumab causes lesions in APOE4 carriers

[mag1]

cerdiwen, Happy New Year!

 

The big excitement is about methylene blue/LMTM.

It looks like it truly is a cure for Alzheimer's.

The numbers overwhelmingly support the efficacy of MB/LMTM.

 

 

They reported the initial phase 2 result in 2008, though it was quite murky at the time.

Then they reported 2 phase 3's in 2016 and it was still quite murky.

 

Now they have published further clarification and the uncertainties have been resolved.

https://www.ncbi.nlm...les/PMC6918900/

 

What happened in the phase 3 trials was the placebo was actually active treatment.

When you take away the treatment effect in the placebo group and maximize the treatment effect in those in the active treatment arms,

then there is a very large treatment effect. It appears that progression is almost stopped for at least roughly 1 year.

 

This is massive massive news.

There can no longer be equivocation, MB/LMTM is an effective Alzheimer's treatment.

 

Feel the love!

A world where Alzheimer's is a treatable illness has arrived!

 

 

Happy New Year everyone!

Let the party begin!

 

 

 

Edited by mag1, 03 January 2020 - 03:06 AM.

[albedo]

From The Lancet commission. Focus on prevention for dementia. Interesting:

 

Dementia prevention, intervention, and care: 2020 report of the Lancet Commission

https://www.thelance...0367-6/fulltext

 

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 dementia 1.PNG   57.54KB   0 downloads

[albedo]

Another reason to check our iron and ferritin levels?

Kletetschka, G., Bazala, R., Takáč, M. et al. Magnetic domains oscillation in the brain with neurodegenerative disease. Sci Rep 11, 714 (2021). https://doi.org/10.1...598-020-80212-5

https://www.nature.c...-80212-5#citeas

[albedo]

"BURLINGAME, Calif., May 13, 2021 /PRNewswire/ -- Pharmaceutical trials for Alzheimer's have failed repeatedly, but a new study, using a fundamentally different approach, has provided the first success: using precision medicine to identify and target the drivers of Alzheimer's or pre-Alzheimer's in each patient, a team of physicians and researchers has posted exciting, positive results in medRxiv, the Yale-backed site for health sciences."

 AD Bredesen.PNG   118.58KB   0 downloads

 

https://www.biospace...mer-s-patients/

https://www.biospace...in-alzheimer-s/

[albedo]

F.D.A. Approves Alzheimer’s Drug Despite Fierce Debate Over Whether It Works

https://www.nytimes....imers-drug.html

[albedo]

Bench-to-bedside drug design could lead to new Alzheimer’s Disease treatments

https://www.gla.ac.u..._820111_en.html

[albedo]

Interesting connection muscle health - brain health mediated by mitochondrial health. Looks logical. I would like to see the study repeated and translated in experimental human studies. With AD drugs failures one after the other "non-pharmacological interventions such as personalised exercise" and, I would add, also personalied nutrition and supplementation (say a-la-Bredesen protocol) rise in importance, IMHO:

 

Giannos, P., Prokopidis, K., Raleigh, S.M. et al. Altered mitochondrial microenvironment at the spotlight of musculoskeletal aging and Alzheimer’s disease. Sci Rep 12, 11290 (2022). https://doi.org/10.1...598-022-15578-9

 

 AD Muscle Mito.PNG   221.9KB   0 downloads

[Harkijn]

Yes, lots of new developments in the  AD field. For instance the paper Reason placed in the News section on the first of the month,  about influenza vaccination. Food for thought!

[albedo]

Yes, lots of new developments in the  AD field. For instance the paper Reason placed in the News section on the first of the month,  about influenza vaccination. Food for thought!

 

Thank you. I missed that!

 

https://www.fightagi...sease/#comments

 

https://content.iosp...sease/jad220361

 

[albedo]

Early Alzheimer’s detection up to 17 years in advance

 

 

https://news.rub.de/...7-years-advance

[mag1]

https://investors.bi...udy-met-primary

 

Biogen / Eisai reported the results of their phase 3 Lecanemab study called Clarity. CDR-sb benefit for those on high dose Lecanemab versus placebo was 0.45 p-value= 0.00005!!

This is set for priority review by the FDA by January 6th, 2023.

[Mind]

The Alzheimer's mystery deepens. Much like the Mankato Nun study (many showed physiological characteristics common in Alzheimer's patients, yet were NOT cognitively diminished), a new study of centenarians reveals that most have all the physical brain indicators of Alzheimer's (A-beta, neuritic plaques, neurofribilatory tangles, hippocampal sclerosis....you name it, they had it), yet they showed little evidence of cognitive decline (for their age). 

 

Repeat, they had all the physical brain damage associated with Alzheimer's yet DID NOT have Alzheimer's.

 

Either there is some key piece of physical evidence that is missing, or we don't fully understand how the brain adapts to and "works around" physical damage. From what I have seen, people who remain mentally, physically, AND socially active as they age, have much lower incidence of Alzheimer's.

 

Still, I think it should be a goal of rejuvenation research to clear up the damage in the brain, even if we don't yet have a definitive theory of Alzheimer's. Young brains do not have all this damage. If we want to rejuvenate, we need to get rid of the damage.

[mag1]

Has Alzheimer's been cured?

First Aduhelm/Lecanemab and now LMTM?

 

 

 

Another massive Alzheimer win!

74% decline in progression on ADAS-cog over 12 months in total Lucidity treatment arm.

 

Better results for the MCI patients.

 

Topline complicated by a faulty placebo-- statistical plan amended to compare against historical controls

 

 

 

"The overall baseline MMSE score was 21 for the study population spanning MCI through to moderate disease. There was minimal decline over the first 12 months in participants receiving the 16 mg/day dose on both coprimary cognitive and functional endpoints (1.3 ADAS-cog₁₁ units and -1.0 ADCS-ADL₂₃ units). The expected decline over 12 months in an untreated population would be approximately 5 units on both scales.

 

In the 105 participants with MCI (baseline MMSE score 23) receiving the 16 mg/day dose, there was statistically significant cognitive improvement of 2 units over the pre-treatment baseline at 6 months (p=0.0002), 12 months (p=0.0391) and 18 months (p=0.0473) on the ADAS-cog₁₃ scale. The mean change on the instrumental activities of daily living subscale of ADCS-ADL also remained above the pre-treatment baseline at 6, 12 and 18 months.

 

In the 147 participants with mild to moderate AD (baseline MMSE 20) receiving 16 mg/day, there was a 2.5 unit cognitive decline in the first 9 months and no further decline over the following 9 months. The functional decline on the ADCS-ADL scale was -2 units at 12 months and -3 units at 18 months representing a reduction in decline of about 75% relative to a published meta-analysis of publicly available placebo decline data from historical trials in mild to moderate AD."

 

 

 

https://taurx.com/ne...ory-submissions

[albedo]

Identification of potential blood biomarkers for early diagnosis of Alzheimer’s disease through immune landscape analysis

 

 

Mild cognitive impairment (MCI) is a clinical precursor of Alzheimer’s disease (AD). Recent genetic studies have reported on
associations between AD risk genes and immunity. Here, we obtained samples and data from 317 AD, 432 MCI, and 107 cognitively
normal (CN) subjects and investigated immune-cell type composition and immune clonal diversity of T-cell receptor (TRA, TRB, TRG,
and TRD) and B-cell receptor (IGH, IGK, and IGL) repertoires through bulk RNA sequencing. We found the proportions of plasma
cells, γδ T cells, neutrophils, and B cells were significantly different and the diversities of IGH, IGK, and TRA were significantly small
with AD progression. We then identified a differentially expressed gene, WDR37, in terms of risk of MCI-to-AD conversion. Our
prognosis prediction model using the potential blood-based biomarkers for early AD diagnosis, which combined two immune
repertoires (IGK and TRA), WDR37, and clinical information, successfully classified MCI patients into two groups, low and high, in
terms of risk of MCI-to-AD conversion (log-rank test P = 2.57e-3). It achieved a concordance index of 0.694 in a discovery cohort and
of 0.643 in an independent validation cohort. We believe that further investigation, using larger sample sizes, will lead to practical
clinical use in the near future.
npj Aging (2022) 8:15 ; https://doi.org/10.1...514-022-00096-9

Edited by albedo, 23 February 2023 - 04:05 PM.

[Thell]

Another functional medicine study based on Recode (Bredesen Protocol). This time, Dr Heather Sandison, of Solcere (her naturopathic clinic) and the founder of Marama (a senior living facility with a goal for residents to return to independent living) was funded by a client with a successful outcome who was also a philanthropist.

 

Observed Improvement in Cognition During a Personalized Lifestyle Intervention in People with Cognitive Decline

 

Methods:
Participants (n = 34) were recruited from the San Diego, CA area. The multimodal intervention included lifestyle changes (i.e., movement, diet, and stress management), nutraceutical support, and medications. It was delivered pragmatically over four clinical visits, and outcome measures were gathered at four study visits, occurring at baseline, one, three, and six months (primary endpoint). Study participants received weekly phone calls for nutrition support throughout study participation. Outcome measures included the Cambridge Brain Sciences (CBS) battery, and the Montreal Cognitive Assessment (MoCA).

Results:
At 6 months, mean MoCA scores improved from 19.6±3.1 to 21.7±6.2 (p = 0.013). Significant improvement was observed in mean scores of the CBS memory domain [25.2 (SD 23.3) to 35.8 (SD 26.9); p < 0.01] and CBS overall composite cognition score [24.5 (SD 16.1) to 29.7 (SD 20.5); p = 0.02]. All CBS domains improved.

Conclusion:
Multiple measures of cognitive function improved after six months of intervention. Our results support the feasibility and impact of a multimodal, individualized treatment approach to OCI, warranting further research.

→ source (external link)

 

Of interest to some may be the supplemental table 2 that lists supplements used. In the study it stated commercially available but I have no idea if that means the all of the ingredients or the finished capsules. There are many on there that I definitely haven't read about before.

 

Also, in the video discussion about the study it was mentioned Bredesen is involved in yet another, larger, study. Hopefully, this time, it will be more controlled and the results more widely accepted.

[Thell]

Just an FYI: in the Dr Sandison study it looks like the baseline nootropic supplement stack is neurohacker Qualia Mind.

[Thell]

Last month, in the Journal of Alzheimer’s Disease, a paper was published, that may be helpful to people wondering what supplements/dietary nutrients they might want to target relating to ALZ.

 

Low Xanthophylls, Retinol, Lycopene, and Tocopherols in Grey and White Matter of Brains with Alzheimer's Disease

 

Abstract
Background: Oxidative stress contributes to pathogenesis and progression of Alzheimer's disease (AD). Higher levels of the dietary antioxidants- carotenoids and tocopherols- are associated with better cognitive functions and lower risk for AD, and lower levels of multiple carotenoids are found in serum and plasma of patients with AD. Although brains donated by individuals with mild cognitive impairment had significantly lower levels of lutein and beta-carotene, previous investigators found no significant difference in carotenoid levels of brains with AD and cognitively normal brains.

Objective: This study tested the hypothesis that micronutrients are significantly lower in donor brains with AD than in healthy elderly brains.

Methods: Samples of donor brains with confirmed AD or verified health were dissected into grey and white matter, extracted with organic solvents and analyzed by HPLC.

Results: AD brains had significantly lower levels of lutein, zeaxanthin, anhydrolutein, retinol, lycopene, and alpha-tocopherol, and significantly increased levels of XMiAD, an unidentified xanthophyll metabolite. No meso-zeaxanthin was detected. The overlapping protective roles of xanthophylls, carotenes, α- and γ-tocopherol are discussed.

Conclusion: Brains with AD had substantially lower concentrations of some, but not all, xanthophylls, carotenes, and tocopherols, and several-fold higher concentrations of an unidentified xanthophyll metabolite increased in AD (XMiAD).

→ source (external link)

 

What I found interesting about this, besides the levels found, is that the items that are lacking seem like an ingredient listing for a macular/ocular support supplement. Given that LLLT is now being clinically shown to help with dementia and a good keto diet is shown to help it would be interesting to find how targeted supplementation and LLLT together would do.

 

Something like the Significant Improvement in Cognition in Mild to Moderately Severe Dementia Cases Treated with Transcranial Plus Intranasal Photobiomodulation: Case Series Report but with a specific supplement cocktail.

[Harkijn]

Another interesting approach is the use of Sildenafil (Viagra), or perhaps preferably Tadalafil, for prevention and cure of Alzheimers. Both supplements cross the BBB and enhance NO status in the brain. This study combines a human study with a review of the science so far:

 

https://alz-journals...1002/trc2.12412

 

In Europe these supplements are freely avaialble. I have taken small amounts almost daily for the last few years because they seem to lower my blood pressure.

[albedo]

Vestin E, Boström G, Olsson J, et al. Herpes simplex viral infection doubles the risk of dementia in a contemporary cohort of older adults: a prospective study. Journal of Alzheimer’s Disease. 2024;97(4):1841-1850.
https://content.iosp...sease/jad230718

 

Wondering about amino acid lysine or long term valacyclorir might be a sort of preventative strategy.

[Galaxyshock]

Immunotherapy Shows Promise as Alzheimer’s Treatment

 

Stress and Trauma Risk Factors for Alzheimer’s

 

Aging Health: Blended Antioxidants Boost Memory and Cognition

 

Hereditary Alzheimer’s Transmitted Via Bone Marrow Transplants

 

Diabetes, Pollution, and Alcohol Amplify Dementia Risk