1230 replies to this topic

[ceridwen]

Of course only my symptoms are coming in thick and fast now. So wonder if I can be of any use

[mag1]

I am sure we would all be interested if brain ultrasound were able to help you.

"Ultrasound devices capable of penetrating the human brain are already being tested for other conditions, with Israeli company InSightec pioneering it ..."

I am not sure whether it is yet commercially available for any indication.

Edited by mag1, 16 March 2015 - 04:32 PM.

[resveratrol_guy]

My concern with utilizing focused ultrasound to disrupt the BBB is the how well it heals. Breaking up the AB is great, having it cleared is great. But if the junctions are damaged to an even worse state what would the ramifications be?

 

You're not supposed to ask such questions! But if you want the answer, you need not look to ultrasound research. Instead, look at the mobile phone lawsuits of late.

 

Some background: several years ago, there was much rancur in the industry regarding the potential for mobile phone radiation to cause brain tumors. Indeed, the probability of acoustic neuroma appears to quadruple with heavy use. But in fairness, this is an extremely rare disease, so the difference is insignificant relative to the sometimes life-saving benefits of mobile phone use. Various scientists got on the bandwagon to explain to us how the thermal radiation was too low to cook the brain, so therefore it was all safe. But any idiot could have told you that microwaves are not heating your head to any dangerous temperature. And unfortunately, these scientists apparently slept through the lecture on molecular orbitals in Quantum Chemistry 101. So they ignored the possibility of changing the energy histogram with respect to protein folding, in other words, the relative fractions of any given protein occupying various excited states, which change their biological dynamics. To put it simply: some proteins will absorb stray photons from the phone which will excite them, resulting in a change to their wave functions, and thus a change to their topology and biological function. Anyone who thinks this is irrelevant paranoia should consider that energy histogram disruption ("population inversion") is precisely the physical process behind laser physics; their intense beams would be physically impossible otherwise.

 

But this is all so 1995. Now, instead of essentially monochromatic 900 MHz CDMA, we have something like 10 or 20 different radios in a typical smart phone, with the power levels rapidly changing in response to variable environmental noise conditions. In other words, your head has become a de facto radiology experiment. Meanwhile, the mobile companies and various mobile phone case vendors exclaim with glee that they produce low levels of (thermal) radiation, or shield against it, respectively. This is about as relevant as saying that neutron bombs don't contain enough ultraviolet to give you a sunburn. If you Google "mobile phone nonthermal radiation" you'll get a mountain of unnerving articles, the significance of which will only be relevant in hindsight. And of course, we need not have a brain tumor epidemic for the effects to be deleterious, because who knows what might happen when you crack open the BBB using 20 different carrier frequencies for several hours a day, let alone if some large fraction of society does this en masse for years.

 

BTW if you're wondering, wired headsets are useless protection: they merely act as waveguides for the mobile phone radiation, delivering it directly to your ears. What you need is either a speaker phone, or acoustic headsets which airgap the radiation. I'm not sure about Bluetooth headsets.

 

Now, the short term effect of this radiation is, according to one study, an improvement in cognitive function. (I didn't bother to dig it out, because I hardly think that mobile phone use is an answer to long term cognitive enhancement, but you can probably find it.) The long term effect is as opaque as the long term effect of LLLT. I just mention all this because it at least suggests that it may be possible to forge a procognitive therapy out of the lessons of mobile phone radiation studies, using the same sort of approach used to tune LLLT, TDCS, TMS, etc. And if nothing else, we can look to these studies for some clues as to the effects of chronic BBB permeability spikes caused by ultrasound.

[ceridwen]

In my youth I was electrically sensitive then I acclimatised to it. Despite dementia still acclimatised to it. Though that will get harder to tell because I always had a delayed reaction to it and if things go on this way I won't know what I've encountered in the last few days. I do not feel worse around pylons like I used to

[ceridwen]

Bees forget which flowers they have visited though. That's 1 of the reasons for colony collapse.Perhaps this whole Alzheimers Disease is triggered by electrical frequencies.

[corb]

http://www.ncbi.nlm....les/PMC4302983/

 

An nice short article about two new theories - bioenergetic and immune - for the onset of AD.

[Nemo888]

IIRC removing plaques did not produce as much benefit as expected. There are a few vaccines that were trialed. Still think TB4 with it's ability to reduce inflammation(IL6), sequester actin and activate stem cells is probably your best bet as a future game changer. It can literally rebuild damaged neurons, something removing plaque did not accomplish.

http://www.prnewswir...-300044323.html

Old age will kill you regardless. But dementia is not how I want to go.

Edited by Nemo888, 16 March 2015 - 08:22 PM.

[mag1]

Yeah, well get ready.

Page 216, "This indicates that, ... the entire process is clearly embedded within the blueprint of the general aging human population and regardless of specific genetic factors that may accelerate the process in some."

Page 217, 100% of 90 year olds have Braak stage 2 or higher.

MCI starts at Braak stage 2.

http://taurx.com/upl...apter-hd[1].pdf

[corb]

Old age will kill you regardless. But dementia is not how I want to go.

 

If we have to compare dementia, CVDs and cancer I'd say dementia will probably remain the hardest to treat in the next 4-5 decades unfortunately.

CVDs are going to become a mere nuisance once stem cell therapies are readily available.

Cancers albeit deadly, at least we have an idea what kind of therapies to research for them.

Neurodegeneration on the other hand is still very much an enigma.

[mag1]

Tau Aggregation Inhibitor Therapy: An Exploratory Phase 2 Study in Mild or Moderate Alzheimer's Disease
Volume 44, Number 2 / 2015
Journal of Alzheimer's Disease

http://iospress.meta...01/fulltext.pdf

[resveratrol_guy]

Tau Aggregation Inhibitor Therapy: An Exploratory Phase 2 Study in Mild or Moderate Alzheimer's Disease
Volume 44, Number 2 / 2015
Journal of Alzheimer's Disease

http://iospress.meta...01/fulltext.pdf

 

Wow, this really didn't work very well. The p values in the statistics are huge in places, indicating lack of numerical confidence. Then even when the therapy "worked", it merely seems to have slowed degeneration. And the dose efficacy formed a tight inverted "U", suggesting that it's probably impractical. I'm sticking with Longvida, pending the discovery of a better aggregation inhibitor. But thanks for sharing. At least, it goes to show just how tough this business is.

[resveratrol_guy]

IIRC removing plaques did not produce as much benefit as expected. There are a few vaccines that were trialed. Still think TB4 with it's ability to reduce inflammation(IL6), sequester actin and activate stem cells is probably your best bet as a future game changer. It can literally rebuild damaged neurons, something removing plaque did not accomplish.

http://www.prnewswir...-300044323.html

Old age will kill you regardless. But dementia is not how I want to go.

 

Do you believe TB4 would be useful, even in the relative absence of inflammation which would be expected in TBI of the sort described in your article above? In other words, do you have any reason to consider it as a dementia prophylactic? Any relevant links? Google is pretty terse on this.

[mag1]

It is a little confusing. The top dose was found not to be absorbed properly.

http://www.ncbi.nlm....pubmed/25320049

The phase 2 results are actually quite impressive when you read through them carefully (and accept that there was some "data management" involved).

For example, "The 138 mg MT/day dose was effectivein preventing clinical decline and the treatment effect was statistically significant (Table 2; p = 0.008,corrected p = 0.047). Therefore, the conclusion of the pre-specified primary efficacy analysis in the mITT population is that treatment at 138 mg/day is effective."

Among the moderate AD patients on 138 mg/day there was quite an effect at 24 weeks (though this would be based on a fairly small number of patients and there could have been selection bias in those who stayed on treatment.)

The results for moderate patients in Figure 2 consistently favor the 138 mg/day treatment.

"Patients randomized to MT138 mg/day, whether mild or moderate at baseline,did not decline and there was a statistically significant
treatment benefit of 2.8 to 5.2 ADAS-cog units in mild and moderate subjects, respectively (see Table 4).These effect sizes represent 96% and 91%, respectively, of the decline seen in the corresponding control arms."

It should be remembered that the mild patients might not have been expected to decline much and this would make it difficult to show a benefit in the trial. Overall the results seem quite positive.

If the current phase 3 trials demonstrate a stabilization of AD patients over 52 weeks, there could be a major celebration soon.

I think if the company were sitting on these results now, they should feel an ethical obligation
to stop the trial early.

Edited by mag1, 17 March 2015 - 01:33 AM.

[ceridwen]

That implies that Alzheimers might be caused by some sort of infection

[ceridwen]

I am inclined to think that anything that works better than Aricept is better than nothing with this frightening disease

[resveratrol_guy]

I am inclined to think that anything that works better than Aricept is better than nothing with this frightening disease

 

I don't think Aricept (or acetylcholinesterase inhibitors generally) fail; I think the brain fails them. In other words, they continue to work just fine, but the rug gets pulled out from under them as phosphotau tangles replace former neurons. As I explained before (but my post was deleted for some reason), there is trial-of-one evidence that this failure can be avoided for at least a decade by lipidated curcumin and other basic antidementia nutrients. I'm not a big fan of anecdotes, but the one described in a multipart series by this YouTube user is compelling, particularly in the absence of anyone else following his particular strategy of potentiating the effects of these inhibitors well beyond the theoretical 2-year max. Yes, a decade-long double-blind placebo controlled trial would be much more informative, if you would like to wait.

Edited by resveratrol_guy, 17 March 2015 - 05:09 AM.

[resveratrol_guy]

If the current phase 3 trials demonstrate a stabilization of AD patients over 52 weeks, there could be a major celebration soon.
 

 

But that's exactly my point: it's a year of stabilization if we read the study optimistically. Coconut oil alone MRI-stabilized Mary Newport's husband for at least 4 years, which says a lot considering that he had obvious brain atrophy when he started dosing.

I never thought I'd say this, but I'm inclined to agree with corb: Alzheimer's is much harder to solve than cancer, especially post-3-bromopyruvate. What we need is a Warburgesque target common to all Alzheimer's patients. I think the closest we've come is the Axon Neurosciences tau vaccine currently in phase 1 trials.

[Kalliste]

Alzheimers seems like something that would need many fixes to be stopped in it's tracks. Maybe a combination of five different treatments + upping physical activity, dietary intervention.

As long as each treatment is performed in isolation nothing might work.

[mag1]

The study only lasted a year.
The study posted the maximum possible results, assuming that reversing the illness using this treatment is not possible.

As far as I am aware no phase 2 trial has ever posted such an overwhelmingly positive result.

I am also impressed with the ketogone approach to Alzheimer's (and in cancer as well- perhaps cancer patients could try Axona). Yet, few (if any) long term randomized trials for this treatment have been done. Ketones might be more about offering a short term cognitive boost than being truly disease modifying. The anecdotal reports for ketone treatment are difficult to assess, while the randomized clinical trials with methylene blue (i.e LMTX) should give us a very good idea about its effectiveness. It is interesting to note that the ketogenic approach appears to have effect in cancer
and possibly AD. Knocking down the cancer cells energy pathway with 3-BP and DCA is easy, though there does not appear to be the same number of targets to knock up the energy supply in AD.

To clarify the reference to 3-Bromopyruvate [Advertising Alert!]

(check out this forum thread) http://www.longecity...e-5#entry716846

3-Bromopyruvate might be a cure for cancer. Recent developments have substantially improved its safety and effectiveness (by several orders of magnitude using nanoparticles).

A related compound DCA has also been enhanced "... Mito-DCA, with three orders of magnitude enhanced potency and cancer cell specificity compared to DCA". http://www.ncbi.nlm....033660/#notes-1


Upgraded 3-BP and DCA when combined might have synergistic effectiveness, as they target the cancer cells respiration pathway in different ways. So, yeah, cancer appears to have been knocked out.

That leaves Alzheimer's as the epidemic scourge of the 21st century. Or maybe not.



A multi-dimensional treatment strategy has already been shown to help in AD.
http://www.impactagi...ull/100690.html(from the top of the APOE forum site)


And again in this study.
http://www.apoe4.inf...fa55dba185fabc6


Alzheimer's disease does not seem to have the same level of complexity as cancer. AD does not appear to have anything comparable to cancer's resistance mechanism. It also appears that AD has a few universally used disease pathways. This will make investment by pharmaceutical companies much more lucrative. Also, as noted above everyone over 90 develops at least Braak stage 2 neuro-degeneration (equal to MCI). So, we are all in this together!

Edited by mag1, 17 March 2015 - 04:41 PM.

[resveratrol_guy]

A multi-dimensional treatment strategy has already been shown to help in AD.
http://www.impactagi...ull/100690.html(from the top of the APOE forum site)


And again in this study.
http://www.apoe4.inf...fa55dba185fabc6


Alzheimer's disease does not seem to have the same level of complexity as cancer. AD does not appear to have anything comparable to cancer's resistance mechanism. It also appears that AD has a few universally used disease pathways. This will make investment by pharmaceutical companies much more lucrative. Also, as noted above everyone over 90 develops at least Braak stage 2 neuro-degeneration (equal to MCI). So, we are all in this together!

 

The FINGER study is impressive because they demonstrated a 2-year sustained improvement in cognitive performance and demonstrated that it was due to factors other than training effect on the brain games used to assess outcomes, and moreover because they did this using 1990s health advice (avoid saturated fats, eat lots of carbs, etc.) What if they had actually hired someone who had read a nutrition study published in past 10 years? The outcome might have been much better still. And they do say that another followup is planned for the 7-year mark, which is obviously important considering that "Postponing of the onset of Alzheimer’s disease by 5 years has been estimated to decrease its prevalence by up to 50% in 50 years". Thanks for sharing.

 

Just the same, you're right: this is everyone's disease, unless you're "lucky" enough to die of a heart attack. It seems that we need to (1) remove phosphotau as fast and as early as possible and (2) ensure that new neurons replace dead ones at a sufficient rate as to maintain brain volume. The problem is that even if tau vaccine and AAV-delivered NGF both get approved, they'll be restricted to the advanced cases, when the real emergency is actually when we can do something about it, in other words, at the initial onset of symptoms.

[mag1]

Hopefully, we won't need too many more of the Finger studies to attract some serious government money. Dementia is already costing American society an amount approaching $1 BILLION per day (for the world as a whole the cost approaches $2 billion per day).

With the results already seen in these lifestyle interventions, they should just do a money drop on the major AD research centers in the US.
It would make quite a bit of sense. The potential rate of return on investment on doing so would be huge! These studies have already proven that these interventions are effective. Replicating them would be a political home run.

The results from the Finger study could translate into 100s of billions of dollars in savings if translated into population wide interventions.

Of note the Finger study did not mention APOE genotype. This is just weird. They mentioned virtually every possible lifestyle factor, though neglected to mention the one genetic risk factor that single handedly makes a massive contribution to the risk of AD in the community. ???
The study also noted that due to their ethical guidelines, the control group was not really a control group. They felt ethically obligated to provide them with lifestyle advice also. So, it is reasonable to expect that the study is understating the benefits of the intervention.

Governments around the world have seen the approaching global dementia epidemic and have finally realized that there is an overwhelming catastrophe on the way. They have committed themselves to provide the resources to address dementia. We will see given the latest study whether or not they are serious about following through on their commitment.

It probably won't be a problem about getting the tau medicines to the people. The methylene blue (LMTX) drug would likely have immediate uptake by those not completely incapable of logical thought. Members of this forum have experimented with micro doses of MB. Perhaps dosing with 10 milligrams per day in those without AD would be reasonable (might have to live with the blue pee)

Edited by mag1, 18 March 2015 - 01:51 AM.

[Nemo888]

IIRC removing plaques did not produce as much benefit as expected. There are a few vaccines that were trialed. Still think TB4 with it's ability to reduce inflammation(IL6), sequester actin and activate stem cells is probably your best bet as a future game changer. It can literally rebuild damaged neurons, something removing plaque did not accomplish.

http://www.prnewswir...-300044323.html

Old age will kill you regardless. But dementia is not how I want to go.

Do you believe TB4 would be useful, even in the relative absence of inflammation which would be expected in TBI of the sort described in your article above? In other words, do you have any reason to consider it as a dementia prophylactic? Any relevant links? Google is pretty terse on this.

I have been wondering if actin sequestration is fundamentally more important to cellular metabolism than previously thought. With more actin the cells motility is vastly improved. If aggregated malformed proteins clog the cell as theorized actin allows the cell to build more room to accomodate. TB4 also increases phagocytosis, removing the malformed proteins.http://www.ncbi.nlm....pubmed/19631707

Combine this with increasing HSF1 with saunas over 19 minutes and you have a very potent cocktail for removing improperly folded proteins without the dangerous immune upregulation that comes with an amyloid vaccine.

[mag1]

http://www.nytimes.c...lowed.html?_r=0

[Logic]

Amyloidosis

Excess antibody protein fragments produced by bone marrow build up in the bloodstream and are then deposited between cells in body tissue.
Chronic infections and inflammatory disease speed up the process.

This points to the elimination of, or at least the minimization of, infection as important in minimising Amaloidosis.

http://www.longecity...-targets/page-3

[mag1]

I should not be so obscure.

 

Biogen is now worth over US $110 billion. Is this the cure for Alzheimer's?

[corb]

It's definitely interesting that we finally have a drug capable of removing amyloids with efficiency.

Now let's see to how much of an increase of life expectancy that translates to people suffering from AD.

[tunt01]

I'd really like to see  Phase I of this liposome treatment.  70% reduction in oligomers.

[mag1]

Biogen rules today. Stock up over $40 per share.

 

These are the best results ever published in Alzheimer's.

[Logic]

Nutrient 'Cocktail' Delays Aging and Extends Life Span


 

1. Vitamin B1
2. Vitamin B3 (niacin)
3. Vitamin B6
4. Vitamin B12
5. Folate
6. Vitamin C
7. Vitamin D
8. Acetyl-L-carnitine
9. Alpha-lipoic acid
10. Acetylsalicylic acid (aspirin)
11. Beta-carotene
12. Bioflavonoids
13. Chromium picolinate
14. Garlic
15. Ginger root extract
16. Ginkgo biloba
17. Ginseng
18. Green tea extract
19. L-Glutathione
20. Magnesium
21. Manganese
22. Melatonin
23. N-Acetyl cysteine
24. Potassium
25. Rutin
26. Selenium
27. Vitamin E
28. Cod liver oil (omega-3)
29. Coenzyme Q10
30. Flax seed oil

http://www.lef.org/M...fe-Span/Page-01

 

From the above it would seem this stack slows you  down a little when young, (Unless they were just enjoying their swim?) but turns you in intellectual youngster eater in old age.

 

It also gives you an 11% - 28% increase in lifespan.

Now if you add C60oo, Lithium, leuco-MB, Astragalus, Purslane, etc....??

Edited by Logic, 21 March 2015 - 01:06 AM.

[niner]

I think it's a little early to start using the word "cure" with Biogen's antibody.  There's a history of anti-amyloid antibodies looking good in phase 1, but flaming out by phase 3.  On the other hand, I think some of you are being too hard on TauRx's drug.  This trial actually had pretty impressive results, despite the formulation difficulties.  The drug wasn't tolerated very well, but this is not their new compound- this is an old trial that used ordinary oxidized methylene blue.  Their new reduced MB, or leuco-MB, is much better tolerated, avoids the availability problems that plagued the oxidized version, and should show even better results.  Those results will be released in 2016.  Keep an eye on that; I think it will be a pretty good drug and will make them a ton of money.  If Biogen's compound works out, and that's a ways down the road, then perhaps it will be synergistic with the TauRx compound.  It's hard to see why the effects would not at least be partially additive.