36 replies to this topic

[Daniel Cooper]

My father is 75 y.o., not overweight, adult onset diabetes controlled for the last 10 yrs with diet only,  He had a double bypass at 65.  Has had a 4 year history of slow cognitive decline which has accelerated somewhat in the last 6 months.  Diagnosed as possibly having Alzheimer's about 3 years ago, but as usual that diagnosis is not entirely certain.

 

I'm constructing a stack with a goal of slowing the progression of his mental decline and improving his situation if at all possible.  I want to come up with four or five things with the best chance of helping him. 

 

This is what I'm thinking so far:

 

MitoQ                                    10mg/day

Nicotinamide                          3000mg/day divided into three doses at meal time.

Curcumin                               250mg/day

Vitamin D3                             2000 IU/day

Glutathione (Reduced)          500mg/day

 

 

The MitoQ is for mitochondrial functioning.  I had considered C60oo, and if available in a capsule form might have gone that route but I am concerned about "patient compliance" in taking something like C60oo.  Simply, if it looks like a "real pill" I think he's more likely to take it.

 

Nicotinamide has several studies behind it for reducing tau protein tangles which are a co-feature of Alzheimer's and might prove to be more significant to the disease progression than amyloid beta plaques. 

 

Studies exist showing that curcumin and D3 taken together have some ability to reduce amyloid beta plaques. 

 

Decreased glutathione levels in the brain seem to be a potential cause for the formation of amyloid beta plagues, so supplementing it seems reasonable.

 

So, how does this look?

 

Edited by Daniel Cooper, 16 November 2014 - 12:09 AM.

[Fenix_]

Have you considered memantine and/or some type of cholinergic drug?

[Daniel Cooper]

Have you considered memantine and/or some type of cholinergic drug?

 

He is currently taking Namenda as well as Aricept.  I believe he has been taking both for about 2 years now.

Edited by Daniel Cooper, 16 November 2014 - 12:29 AM.

[Fenix_]

Oh well at least you know his doctors are on top of things. I know nefiracetam was also developed to treat alzheimers and is prescribed clinically in Japan. Also, Bacopa might be a good choice as a general well-being supportive supplement.

Edited by Fenix_, 16 November 2014 - 01:00 AM.

[Turnbuckle]

I'd add a couple of grams of vitamin C (with flavonoids).

 

http://www.ncbi.nlm....les/PMC4011065/

 

Ascorbic Acid and the Brain: Rationale for the Use against Cognitive Decline...In general, plasma levels of AA [ascorbic acid] in the above studies have been consistently observed to be around 20 µM in patients with AD, i.e., about the half of those measured in controls [7,125,127]. In agreement with studies showing that plasma AA levels are depleted in AD independent of dietary intake, peripheral AA depletion in AD patients with respect to controls has been repeatedly confirmed after correction for age, gender, fruit and vegetable intake, and comorbidities [7,125,127]. Another element strongly suggestive of low AA levels as a co-causal factor for neurodegeneration and AD rather than epiphenomenon of AD is the observation of similarly depleted plasma AA levels in both MCI patients and AD patients compared to controls [7]. Comparison of all these studies where effects are on particular subtypes of memory of cognition, versus disease risk, may indicate that avoiding deficiency, and optimally supplementing with AA may benefit different facets of cognitive health. Nevertheless, the directions of effect seem to be in the same direction.

 

 

This article might also be of interest--Nutrition and prevention of Alzheimer’s dementia

Edited by Turnbuckle, 16 November 2014 - 01:28 AM.

[abelard lindsay]

You might want to add this to your research pile:

 

http://www.ncbi.nlm....blue alzheimers

 

There's also plenty of discussion about methylene blue on this board.  TauRX is doing clinical trials on methylene blue right now as a treatment for alzheimers.

 

http://en.wikipedia....ninium_chloride

 

http://taurx.com/015...ical-study.html

 

What's funny is this stuff has been around as a medicine since the 1890s:

 

http://en.wikipedia....ne_blue#History

Edited by abelard lindsay, 16 November 2014 - 02:44 AM.

[Shorty]

Nitromemantine

[Daniel Cooper]

I'd add a couple of grams of vitamin C (with flavonoids).

 

http://www.ncbi.nlm....les/PMC4011065/

 

Ascorbic Acid and the Brain: Rationale for the Use against Cognitive Decline...In general, plasma levels of AA [ascorbic acid] in the above studies have been consistently observed to be around 20 µM in patients with AD, i.e., about the half of those measured in controls [7,125,127]. In agreement with studies showing that plasma AA levels are depleted in AD independent of dietary intake, peripheral AA depletion in AD patients with respect to controls has been repeatedly confirmed after correction for age, gender, fruit and vegetable intake, and comorbidities [7,125,127]. Another element strongly suggestive of low AA levels as a co-causal factor for neurodegeneration and AD rather than epiphenomenon of AD is the observation of similarly depleted plasma AA levels in both MCI patients and AD patients compared to controls [7]. Comparison of all these studies where effects are on particular subtypes of memory of cognition, versus disease risk, may indicate that avoiding deficiency, and optimally supplementing with AA may benefit different facets of cognitive health. Nevertheless, the directions of effect seem to be in the same direction.

 

 

This article might also be of interest--Nutrition and prevention of Alzheimer’s dementia

 

Thanks for the advice Turnbuckle.  At a couple of grams of C per day do I need to worry much about stomach upset?

 

 

[Daniel Cooper]

Nitromemantine

 

 

Nitromemantine indeed looks interesting, but not yet approved correct?  Is anyone selling this?

 

 

[Turnbuckle]

 

I'd add a couple of grams of vitamin C (with flavonoids).

 

http://www.ncbi.nlm....les/PMC4011065/

 

Ascorbic Acid and the Brain: Rationale for the Use against Cognitive Decline...In general, plasma levels of AA [ascorbic acid] in the above studies have been consistently observed to be around 20 µM in patients with AD, i.e., about the half of those measured in controls [7,125,127]. In agreement with studies showing that plasma AA levels are depleted in AD independent of dietary intake, peripheral AA depletion in AD patients with respect to controls has been repeatedly confirmed after correction for age, gender, fruit and vegetable intake, and comorbidities [7,125,127]. Another element strongly suggestive of low AA levels as a co-causal factor for neurodegeneration and AD rather than epiphenomenon of AD is the observation of similarly depleted plasma AA levels in both MCI patients and AD patients compared to controls [7]. Comparison of all these studies where effects are on particular subtypes of memory of cognition, versus disease risk, may indicate that avoiding deficiency, and optimally supplementing with AA may benefit different facets of cognitive health. Nevertheless, the directions of effect seem to be in the same direction.

 

 

This article might also be of interest--Nutrition and prevention of Alzheimer’s dementia

 

Thanks for the advice Turnbuckle.  At a couple of grams of C per day do I need to worry much about stomach upset?

 

 

 

 

Nothing like niacin, which I took in gram quantities for years. If there is a problem, adding a tablet of Pepcid should fix it. Or better yet, switching to magnesium ascorbate.

 

Though in this study, an antioxidant combination with C was not impressive.

Edited by Turnbuckle, 17 November 2014 - 02:25 PM.

[SanjayK]

Increase the ketone production.

 

I'd go for coconut oil or MCT oil.  Alzheimers is an insulin sensitivity to the brain -diabetes for the brain- so to speak.  Coconut oil has been shown to help a great deal.

[resveratrol_guy]

@ Turnbuckle: Sounds like you decreased your niacin intake -- why? I did find a few papers that seem to support its antialzheimers effects, but perhaps you have a favorite you could share. (Lurkers, google "niacin flush" before you try taking it.) [EDIT: Turnbuckle preemptively answered these questions here on 11/9/2014.]

 

@ Daniel Cooper: You might try lipidated curcumin (Longvida and others) instead of the normal stuff that's found in turmeric. It supposedly crosses the blood-brain barrier more easily. Oh yeah, and cacao (and 100 other nootropics on this forum).

 

@ SanjayK: Excellent point; MCTs are pretty clearly beneficial to "type 3 diabetes" / "metabolic Alzheimers" victims within digestive delay time. HOWEVER, if no benefits are evident @ 10-20 ml after a few days, then I would suggest the possibility that this is a dementia of more vascular pathology, as opposed to tauopathy or choline paucity. That would be good news, as vascular pathology is more treatable IMO (but probably more morbid if untreated).

 

Alzheimers is clearly like cancer: it's a catch-all bucket for many different diseases. I believe that the overwhelming majority of Alzheimers cases begin with vascular pathology (pericyte dysfunction, arterial plaque, etc.), but end up with beta amyloidosis, tauopathy, neurotransmitter imbalance, etc. Because the medical community has a do-nothing-until-its-too-late approach to this disease, many researchers have concluded that it's a disease of neurons, which I think is about as reasonable as saying that old age is a disease of gray hair. No doubt there are genetic components like ApOE4, but young people with this gene can think just fine, so something occurs to trigger the avalanche of pathology. Early intervention is key, as in any chronic disease.

 

Edited by resveratrol_guy, 19 November 2014 - 05:24 PM.

[Flex]

Sorry to hear that.

I´ve read in reddit/science that beta amiloid is responsible after all and not tau proteins.

Hope that helps somehow

 

[APBT]

Here’s a thread that’s been on-going since July 2008: The Latest Alzheimer’s Research

[Steve Zissou]

Here is the perfect thing for your father. I'm try to get mine on this too. He only wants to take a few supplements however. You have to search for the paper on google.

 

http://newsroom.ucla...-for-first-time

[resveratrol_guy]

Steve, looks like a decent antialzheimers regimen. (And I have no argument with the authors' hypothesis that monotherapy is basically useless.) But I have no doubt Longecity could improve upon it. Stem cell therapy and c60oo would be good adjuncts, for instance. Here is the original paper, which has some lovely data-rich tables:

 

http://www.impactagi...ull/100690.html

 

[Shorty]

 

Nitromemantine

 

 

Nitromemantine indeed looks interesting, but not yet approved correct?  Is anyone selling this?

 

I believe Isochroma-Reborn has acquired and used it. You can PM him but I think it would be great if he could chime in and talk about his experience and sources in this thread. My father too suffers from some Dementia related symptoms following a stroke so you're definitely not the only one interested in possible treatments.

[blood]

Steve, looks like a decent antialzheimers regimen. (And I have no argument with the authors' hypothesis that monotherapy is basically useless.) But I have no doubt Longecity could improve upon it. Stem cell therapy and c60oo would be good adjuncts, for instance. Here is the original paper, which has some lovely data-rich tables:

http://www.impactagi...ull/100690.html

Probably wouldn't hurt to add micro-dose lithium (300 mcg to 10 mg or more/ day) to the Bredesen protocol:
http://www.ncbi.nlm....pubmed/22746245

Example product:
http://www.swansonvi...e-5-mg-100-caps

Edited by blood, 27 November 2014 - 11:59 AM.

[5IMON]

Cerebrolysin if it's vascular dementia- google it

[Mind_Paralysis]

Count me in as another supporter of Nitromemantine. Well, in theory.

 

It hasn't been approved, but the basic science seems quite logical to me, as Namenda ( Memantine) was supposed to do the same thing, but ultimately ended up being too darn weak.

 

A more potent NMDA-antagonist might be able to do the job properly.

[blood]

High dose mixed tocotrienols were recently found to halt further progression of white matter lesions in patients with cardiovascular risk factors (& white matter lesions). I mention this, as you say your father has had a bypass.
 

Clinical investigation of the protective effects of palm vitamin E tocotrienols on brain white matter.

Gopalan Y1, Shuaib IL, Magosso E, Ansari MA, Abu Bakar MR, Wong JW, Khan NA, Liong WC, Sundram K, Ng BH, Karuthan C, Yuen KH.

Abstract

BACKGROUND AND PURPOSE:

Previous cell-based and animal studies showed mixed tocotrienols are neuroprotective, but the effect is yet to be proven in humans. Thus, the present study aimed to evaluate the protective activity of mixed tocotrienols in humans with white matter lesions (WMLs). WMLs are regarded as manifestations of cerebral small vessel disease, reflecting varying degrees of neurodegeneration and tissue damage with potential as a surrogate end point in clinical trials.

METHODS:

A total of 121 volunteers aged ≥35 years with cardiovascular risk factors and MRI-confirmed WMLs were randomized to receive 200 mg mixed tocotrienols or placebo twice a day for 2 years. The WML volumes were measured from MRI images taken at baseline, 1 year, and 2 years using a validated software and were compared. Fasting blood samples were collected for full blood chemistry investigation.

RESULTS:

According to per-protocol (88 volunteers) and intention-to-treat (121 volunteers) analyses, the mean WML volume of the placebo group increased after 2 years, whereas that of the tocotrienol-supplemented group remained essentially unchanged. The mean WML volume change between the 2 groups was not significantly different (P=0.150) at the end of 1 year but was significant at the end of 2 years for both per-protocol and intention-to-treat analyses (P=0.019 and P=0.018). No significant difference was observed in the blood chemistry parameters between the 2 groups.

CONCLUSIONS:

Mixed tocotrienols were found to attenuate the progression of WMLs.

KEYWORDS:
magnetic resonance imaging; tocotrienols

PMID: 24699052

Edited by blood, 30 November 2014 - 12:53 PM.

[Area-1255]

Pitolisant might also be good, especially if he has general awareness / awakeness problems.....

But....if he has a history of allergies/asthma, it might not be good.

Edited by Area-1255, 30 November 2014 - 05:20 PM.

[Mind_Paralysis]

Pitolisant might also be good, especially if he has general awareness / awakeness problems.....

But....if he has a history of allergies/asthma, it might not be good.

 

Interesting... does Pitolisant work by affecting the histaminergic networks then? Or does that have to do with a potential effect on glutamate? I hear that apparently histamine and glutamate are deeply connected, and an effect on one, usually affects the other as well - as a reaction to the perceived imbalance.

 

Is that assumption correct, btw?

[Flex]

 

 

Interesting... does Pitolisant work by affecting the histaminergic networks then? Or does that have to do with a potential effect on glutamate? I hear that apparently histamine and glutamate are deeply connected, and an effect on one, usually affects the other as well - as a reaction to the perceived imbalance.

 

Is that assumption correct, btw?

 

 

I would also gladly know that because  I´m using Mirtazepine on a every day basis for sleep and wonder whether my, allready bad, memory is partly affected by Mirtazepine.

[Area-1255]

 

Pitolisant might also be good, especially if he has general awareness / awakeness problems.....

But....if he has a history of allergies/asthma, it might not be good.

 

Interesting... does Pitolisant work by affecting the histaminergic networks then? Or does that have to do with a potential effect on glutamate? I hear that apparently histamine and glutamate are deeply connected, and an effect on one, usually affects the other as well - as a reaction to the perceived imbalance.

 

Is that assumption correct, btw?

 

By raising histamine, you generally lower glutamate levels depending on whether histamine H3's are being blocked, if you block those, then that is the most FAVORABLE HISTAMINE ENHANCEMENT, because GABA will go up as well as acetylcholine and dopamine, GABA will go up enough to counter glutamate, while the other NT's preserves and enhances memory, explains why my racing thoughts went down when I INCREASED histamine by means of pitolisant...it's because histamine's negatives tend to come almost entirely by it;'s own feedback against itself, and because h3r's also have non-histamine locations, such as serotonin sites, dopamine and GABA as well as cholinergic sites...so you get a five fold increase in all of the above with h3 antagonists...both by HISTAMINERGIC AND NON-HISTAMINERGIC NETWORKS.

 

Also , one would expectedly have other anxiolytic effects from any drug in the H3R antagonist class, because H3R's are also separate negative modulators of dopamine D2 receptor function.

 

 

Neuropharmacology. 2008 Aug;55(2):190-7. doi: 10.1016/j.neuropharm.2008.05.008. Epub 2008 May 16.

Interactions between histamine H3 and dopamine D2 receptors and the implications for striatal function.

Ferrada C1, Ferré S, Casadó V, Cortés A, Justinova Z, Barnes C, Canela EI, Goldberg SR, Leurs R, Lluis C, Franco R.

Author information

 

Abstract

The striatum contains a high density of histamine H(3) receptors, but their role in striatal function is poorly understood. Previous studies have demonstrated antagonistic interactions between striatal H(3) and dopamine D(1) receptors at the biochemical level, while contradictory results have been reported about interactions between striatal H(3) and dopamine D(2) receptors. In this study, by using reserpinized mice, we demonstrate the existence of behaviorally significant antagonistic postsynaptic interactions between H(3) and D(1) and also between H(3) and dopamine D(2) receptors. The selective H(3) receptor agonist imetit inhibited, while the H(3) receptor antagonist thioperamide potentiated locomotor activation induced by either the D(1) receptor agonist SKF 38393 or the D(2) receptor agonist quinpirole. High scores of locomotor activity were obtained with H(3) receptor blockade plus D(1) and D(2) receptor co-activation, i.e., when thioperamide was co-administered with both SKF 38393 and quinpirole. Radioligand binding experiments in striatal membrane preparations showed the existence of a strong and selective H(3)-D(2) receptor interaction at the membrane level. In agonist/antagonist competition experiments, stimulation of H(3) receptors with several H(3) receptor agonists significantly decreased the affinity of D(2) receptors for the agonist. This kind of intramembrane receptor-receptor interactions are a common biochemical property of receptor heteromers. In fact, by using Bioluminescence Resonance Energy Transfer techniques in co-transfected HEK-293 cells, H(3) (but not H(4)) receptors were found to form heteromers with D(2) receptors. This study demonstrates an important role of postsynaptic H(3) receptors in the modulation of dopaminergic transmission by means of a negative modulation of D(2) receptor function.

 

Edited by Area-1255, 30 November 2014 - 06:44 PM.

[Mind_Paralysis]

Interesting.

So next-gen allergy-pills increases glutamate, dopamine and serotonin -activity? Sounds pretty great! = )

 

When I search online tho', the documentation and implementation of h3 antagonists is pretty thin tho'... Are there any trials and fresh studies that shed some more light on their potential application?

[Daniel Cooper]

Guys,

 

I'm reviving this thread.  Down with my parents for the holidays and my father has taken an obvious decline.  Less communicative and has started some odd vocalizations (constant moaning though he says he's not in paid).  He still recognizes me and can hold a conversation but clearly in the last 6 months things have gone downhill.

 

The easy straightforward things have been tried.  Given where he's at it's time to go up the risk curve  a bit.  I'm thinking NSI-189 or Dihexa.  Anyone with anything thoughts on this?

 

 

 

[stefan_001]

I would add morning and nighttime 250mg NR, I see it as a foundation layer to keep the cell energy up. My dad had a bad fall on his head and they put in an MRI scanner. They came to double check his age and then concluded he must have good genes.......They are both 75 years old and they feel it energizes them. Ofcourse that is something else than helping with Alzheimer's, but keeping your farther active and having energy I think is important. Have you considered Ginkgo? Seems to be used a lot in Germany for Alzheimer's. I asked my patents to start taking it.
Best wishes,
Stephan

[noot_in_the_sky]

What is your father currently taking?

[KingBrown]

If you can get hold of an absorbable form of Curcumin (e.g one also containing Bioperine) this has been shown to help reduce levels of beta amyloid (http://www.ncbi.nlm....les/PMC2781139/) as well as be protective of BDNF levels.

 

 

Edited by KingBrown, 26 December 2015 - 09:33 AM.