34 replies to this topic

[Phlogiston]

Last week I was diagnosed with Mild Cognitive Impairment.

 

For those not familiar with this diagnosis, it is much more ominous than it sounds. It refers to cognitive impairment which cannot be explained by age, emotional condition or medication regimen. Some sources online emphasize that not everyone with MCI progresses to full blown dementia, but other sources state simply that it is the earliest phase of dementia. I would welcome any educated feedback on the risk of progression.

 

For three months I have been following a protocol for reversing age related memory loss developed at the Memory Disorders clinic at UCLA Medical School. I have attached the journal article containing the protocol since I cannot link to it.

 

I have been eating low carb - zero grain, doing aerobic exercise like it's my job, and taking all the usual neuro - supps:  Resvertrol, NAC, citicoline, circumin, ashwagandha, bacopa,and Omega 3's. Today I added centrophenoxine to the list.  This in addition to a multi-vitamin and the usual anti-oxidants.

 

Today I contacted a physician I know who has been board-certified as both a neurologist and a psychiatrist. She stated that the UCLA protocol is "cutting edge" and probably my best chance at reversing my cognitive decline.

 

One "Achilles heel" I am aware of in my program is that I only fully discontinued Ambien a couple weeks ago. I had not been aware, until a web search, that there are many anecdotal accounts of Ambien causing the kind of cognitive problems I have experienced. We will see if Ambien detox helps turn the tide.

 

I would welcome any feedback from the board. I know that many of you have academic training in relevant fields.

 

 

Attached Files

•  REVERSING MEMORY LOSS.pdf   794.33KB   36 downloads

[Wingless]

What did they do to determine this diagnosis? Brain scans? Or was it a test of sorts?

 

I do not have academic training or anything of that sort, though I can tell you right now that getting quality sleep is probably the most important thing you will ever do for general cognitive health.

Edited by Wingless, 03 September 2015 - 01:13 AM.

[gamesguru]

It can be due to many causes, eg) vascular, lewy-body or Alzheimer dementia, heavy metal or other chemical exposure, (dietary) immunodefiency and herpetic inflammation, etc.

 

The regimen is impressive, but I would perhaps exercise not too much, remove the NAC, centro and resv, swap the citicholine and ω-3s for ALCAR/PS and salmon/sardines, and add healthful grains eg) quinoa, Ezekiel bread, etc.

 

Consume pepper with curcumin; consider adding to the regimen ginger, ginkgo, ginseng, kava, CBD(if available), and Japanese tea.

Edited by gamesguru, 03 September 2015 - 02:41 AM.

[Dolph]

Yes, stuff like Ambien and Benzos is evil when it comes to cognitive impairment. Good decision to get off of it.

 

How old are you?

Did you consider trying another dietary aproach? I remember not feeling exactly like the sharpest knive in the drawer when I tried LC-dieting ~15 years ago and I heard the same from several other people..

[Phlogiston]

Dolph, the reason I'm going with the low carb approach is that a lot of the science now indicates that high blood sugar, high body fat, and the high insulin levels that the body uses to process carb consumption are neuroinflammatory and contribute to brain aging.

 

People (like myself) who are not diabetic but have higher than normal blood sugar have twice the risk for dementia as people whose blood sugar is maintained at low-normal levels. The UCLA protocol emphasizes reducing A1C and fasting insulin, hence the grain free recommendation, and the recommendation that people fast for 12 hours between dinner and breakfast.

[gamesguru]

Yeaaaah maaan, i mean my grandpa ate quinoa for breakfast and he died eventually, so that stuff can't be too good for you.

 

Quinoa protective effects against obesity-induced intestinal inflammation

Edited by gamesguru, 03 September 2015 - 04:13 PM.

[Bateau]

Since you seem to be into traditional herbals that have lots of evidence, Id also suggest looking into polygala tenuifolia and centella asiatica (gotu kola), both very promising.

 

You and your physician might want to look into low-dose Levetiracetam (Keppra). It's used as an anti-epileptic drug, but in a huge screening of epileptic drugs led by Dr. Michela Gallagher, Levetiracetam was the most promising by far.

 

Small doses of levetiracetam (less than whats used for epilepsy) stops the over-activation of the CA3 region of the hippocampus that is classic in mild cognitive decline. If you can get tested and are shown to have this issue, this is a very promising treatment.

 

If you're looking to control blood sugar, HbA1c & insulin the most promising supplements are Berberine, Jiaogulan, Salacia, and Black Cumin (the spice). Berberine is on a pharmaceutical level in its level of science and its potency and has been put in trails compared to metformin (glucophage) in both diabetics and women with PCOS and is comparable. The other three (particularly jiaogulan IMO) also look really promising and very healthy, but berberine is just on a different level. Not to be sensationalist, but it makes resveratrol look like a joke when it comes to human evidence of health benefits.

 

Out of those four for controlling blood sugar, Jiaogulan particularly also looks incredibly neuroprotective FWIW

Edited by Bateau, 03 September 2015 - 06:03 PM.

[Dolph]

It would be an outright crazy idea to chose berberine over metformin. The trials you mentioned were small and lasted only several weeks. There is absolutely no way to judge the safety of this stuff. And the disaster of the DPP-4 inhibitors teached us the hard way that glucose lowering is not everything.

Edited by Dolph, 03 September 2015 - 06:02 PM.

[Bateau]

It would be an outright crazy idea to chose berberine over metformin. The trials you mentioned were small and lasted only several weeks. There is absolutely no way to judge the safety of this stuff. And the disaster of the DPP-4 inhibitors teached us the hard way that glucose lowering is not everything.

 

Um, no it wouldn't. OP doesnt have full blown T2DB, just high blood sugar. OP can't even get metformin. Berberine is very valid option for an individual to try to control blood sugar

 

Not to mention metformin monotherapy has been shown to INCREASE the risk of Alzheimer's, unless combined with insulin treatment, which again, OP shouldn't be doing.

 

If you're talking about potential oncogenic effects by bringing up DPP-4, berberine is considered incredibly promising as a cancer-treatment and inhibits growth in pretty much every cancer cell line ever tested.

 

The stuff has been fed to rodents for their entire life and had no negative side effects. Also this stuff have been used extensively in china for over 50 years, used to treat diabetes for over 10, and in herbal form has been used to lower blood sugar for centuries. It's never shown any health concerns.

Edited by Bateau, 03 September 2015 - 06:13 PM.

[Dolph]

That's just wrong. The best available evidence clearly indicates a reduced(!) risk of dementia in metformin users in any case. There is NO data whatsoever for bereberine. You could as well put all your money on black or red. And no, rodent data is of no help in such a case.

http://www.medscape....warticle/807886

Edited by Dolph, 03 September 2015 - 06:16 PM.

[gamesguru]

Virtually any flavonoid-rich plant is anti-diabetic

Mammals evolved among plants for millions of years.  We depend on them for medicinal qualities, they depend on us to spread their seed (well, not the ones trying to poison us).  A strong synergy has developed between us.

 

Modulation of Glucose Transporter Protein by Dietary Flavonoids

A number of studies hypothesized that some flavonoids may increase GLUT-4 expression and PI3K/Akt activity leading to restore insulin sensitivity and might be a viable therapeutic avenue for treating diabetes. It has been reported that epicatechin reinforce the insulin signaling pathway by activating key proteins, such as IR/IRS, PI3K/AKT pathway and AMPK, and regulates the glucose production through AKT and AMPK modulation in HepG2 cells ¹¹². A more recent study on antihyperglycaemic effect of epicatechin, demonstrated that this flavonoid compound reduced the high glucose-induced insulin signaling blockade by preventing the decrease of tyrosine phosphorylated and total IR, IRS-1 and IRS-2 levels, the inhibition of PI3K/AKT and AMPK pathways, and the increase of IRS-1 Ser636/639 phosphorylation values in HepG2 cell line ¹¹¹. In addition, it has been reported that EGCG attenuated insulin resistance by increasing IRS-1 serine phosphorylation in vitro ¹³⁹ and in vivo ^{140, 141}.

 

Anthocyanins derived from purple sweet potato has shown to remarkably restore the impairment of the IRS1/PI3K /Akt insulin signaling pathway in the livers of high fat diet-treated mice ⁷⁸. Lou, Zhang ¹⁴², claimed that IL-6 and TNF-α are involved in the development of insulin resistance in hepatocytes. The result of this study confirmed that berberine effectively inhibited palmitate-induced IL-6 and TNF-α and attenuated insulin signaling cascade by modification of Serin/Threonine phosphorylation of insulin receptor substrate-1(IRS-1) and downstream Akt. Kaempferitrin and rutin have been identified to stimulate AKT phosphorylation as well as synthesis and translocation of GLUT-4 in adipocytes and skeletal muscle cells ^{83, 143, 144}. Myricetin has been evaluated to possess promising activities on improving insulin sensitivity by phosphorylation IR/IRS-1 and PI3K/AKT, which subsequently effect translocation of GLUT-4 in soleus muscles of fructose chow-fed rats

Edited by gamesguru, 03 September 2015 - 06:21 PM.

[Bateau]

That's just wrong. The best available evidence clearly indicates a reduced(!) risk of dementia in metformin users in any case.

 

The "best available evidence" is way less "clear" than you suggest.

 

As compared with nonusers, long-term users of 60 or more metformin prescriptions were at greater risk of developing AD (adjusted OR (AOR) = 1.71, 95% CI = 1.12-2.60), but there was no consistent trend with increasing number of prescriptions. Long-term use of other antidiabetic drugs such as sulfonylureas (AOR = 1.01, 95% CI = 0.72-1.42), thiazolidinediones (AOR = 0.87, 95% CI = 0.31-2.40), or insulin (AOR = 1.01, 95% CI = 0.58-1.73) was not related to an altered risk of developing AD.

→ source (external link)

 

Participants with diabetes (n=126) had worse cognitive performance than participants who did not have diabetes (n=1,228; adjusted odds ratio 1.51 [95% CI 1.03-2.21]). Among participants with diabetes, worse cognitive performance was associated with metformin use (2.23 [1.05-4.75]).

→ source (external link)

 

Epidemiological, clinical and experimental evidence suggests a link between type 2 diabetes and Alzheimer's disease (AD). Insulin modulates metabolism of beta-amyloid precursor protein (APP) in neurons, decreasing the intracellular accumulation of beta-amyloid (Abeta) peptides, which are pivotal in AD pathogenesis. The present study investigates whether the widely prescribed insulin-sensitizing drug, metformin (Glucophage®), affects APP metabolism and Abeta generation in various cell models. We demonstrate that metformin, at doses that lead to activation of the AMP-activated protein kinase (AMPK), significantly increases the generation of both intracellular and extracellular Abeta species. Furthermore, the effect of metformin on Abeta generation is mediated by transcriptional up-regulation of beta-secretase (BACE1), which results in an elevated protein level and increased enzymatic activity. Unlike insulin, metformin exerts no effect on Abeta degradation. In addition, we found that glucose deprivation and various tyrphostins, known inhibitors of insulin-like growth factors/insulin receptor tyrosine kinases, do not modulate the effect of metformin on Abeta. Finally, inhibition of AMP-activated protein kinase (AMPK) by the pharmacological inhibitor Compound C largely suppresses metformin's effect on Abeta generation and BACE1 transcription, suggesting an AMPK-dependent mechanism. Although insulin and metformin display opposing effects on Abeta generation, in combined use, metformin enhances insulin's effect in reducing Abeta levels. Our findings suggest a potentially harmful consequence of this widely prescribed antidiabetic drug when used as a monotherapy in elderly diabetic patients.

→ source (external link)

 

Edited by Bateau, 03 September 2015 - 06:41 PM.

[Bateau]

 

Virtually any flavonoid-rich plant is anti-diabetic

Mammals evolved among plants for millions of years.  We depend on them for medicinal qualities, they depend on us to spread their seed (well, not the ones trying to poison us).  A strong synergy has developed between us.

 

 

 

 

Yea what makes berberine unique is that it actually confers a huge amount of health benefits when supplemented, and has been shown to do so in over 100 studies

 

That can't be said with other flavonoids or their parent plants.

 

Edited by Bateau, 03 September 2015 - 06:40 PM.

[Major Legend]

As I said in the other thread. I feel anecdotally Alpha GPC has more obvious effects compared with Citocholine.

 

I highly highly recommend taking noopept with lions mane (1 gram per dose) for cognitive impairment. NAC is great too. I love Astaxanthin (even if it's just for it's ocular blood flow boost) but I think I will replace that with nanocarbons soon.

 

The Life Extension Mix from Life Extension (Pretty Pricey) has all the herbs you would want for brain health. Blueberry extract is certainly something I would be looking for too.

 

You should read the Grain Brain by Dr Perlmutter too, but I think it's the same thing as the UCLA protocol. Basically less sugar = less neuroinflammation. The older you get the less your body

deals with elevated sugar levels effectively increasing the damage dealt. However the less sugar approach wouldn't cause significant neuroregeneration. To get better from cognitive impairement you need:

 

1) Active chemicals that enhance synaptic performance artificially

2) Herbs and chemicals that endorse formation of new synapses quickly, so you can relearn things quicker and strengthen existing connections more.

 

also it's a balancing act in my opinion

yeah technically low sugar is better for you, but if you do it too much you can become fatigued instead, and ketosis doesn't work for everyone.

 

As for Metformin. I am not 100% convinced messing with bloodsugar homeostasis is a great idea, given how drugs have a good tendency to destroy whatever equilibrium your body is having against sugar itself. The metformin

idea is still a theory to me.

 

Metformins half life also means that it might create things like sugar rebound or other things. I would say maybe even plenty of diabetics who used it might be worst off, because it also can make you more

hungry, which makes you eat more, which just removes the point of it. Unless you can stick to a rigid schedule its hard to keep Metformin at controlled plasma concentrations, so its likely to be going up and down and up in down.

 

I also know a few people that became better after they started taking less metformin, which does make me question the drug a little bit, besides if metformin was so effective why are diabetics still dying much earlier than non-diabetics.

 

Avoiding processed foods, sugars and gluten, and intermittent fasting plus 7 minutes of exercise everyday is still the thing that works.

 

If I eat a bucket of ice cream I do actually take metformin, so I do see it as a sort of band aid, but long term use on a non-diabetic? I'm not so sure.

 

my two cents - hope this helps.

Edited by Major Legend, 03 September 2015 - 10:23 PM.

[Major Legend]

Oh I should throw MitoQ and PPQ into there too, but I think your treatment cost is starting to skyrocket lol.

 

oh and brain entrainment, you need a good device though.

Edited by Major Legend, 03 September 2015 - 10:33 PM.

[gamesguru]

Alpha GPC

 

What would you think of these?

ALCAR/PS

[Phlogiston]

Bateau, thanks for the information on metformin.

 

I've been on a small dose of Metformin (1000 mg) for a couple years, due to some blood sugar readings in the prediabetic range. Basically, it allowed me to carb binge while still having nominally normal numbers for fasting glucose and A1C. However, several months ago a blood test showed that I had great numbers for fasting glucose (98) and A1C (5.4) but still had a fasting insulin reading of 14, indicating that despite the Metformin I had significant insulin resistance and that I was probably working my beta cells way too hard. Since then I have lost 20 pounds while eating low carb, so I may be able to look at eliminating the Metformin.

 

However, until reading your postings I thought that Metformin was an all-around beneficial med, due in part to having seen it endorsed here as a life-extension supp. 

[Bateau]

Bateau, thanks for the information on metformin.

 

However, until reading your postings I thought that Metformin was an all-around beneficial med, due in part to having seen it endorsed here as a life-extension supp. 

 

Metformin is still pretty damn amazing, the issues with b12 absorption and possible effects on cognition are the only downsides AFAIK. Probably worth the decreased risk of cardiovascular disease, cancer, diabetes, etc.

 

Berberine should confer similar health benefits. It doesn't have the vitamin b12 issues, but as far as long term effects on cognition, we aren't sure what it does.

[Phlogiston]

Major Legend, I am also using Life Extension's Mitochondrial Energy Optimizer supp. It contains a lot of the supps that are recommended for cognitive issues, but I'm not sure about the dosages / proportions:

 

Vitamin B6 100 mg

Carnosine 1000 mg

Acetyl -L-Carnitine arginate 675 mg

Benfotiamine  150 mg

R-Lipoic Acid  150 mg

PQQ  10mg

Luteolin  8mg

 

That doesn't sound like much PQQ, or is PQQ believed to be effective in such a small dosage?

 

 

[gamesguru]

PQQ occurs in foods at like 10ng/g, in the human body at 2ng/g^[1] ... so there's only like 150mcg in the average adult!  So forgoing bioavailability issues, absolutely: compared with dietary sources (~20mcg daily), 10mg is huge.

You can increase CoQ10 levels by similar dietary adjustments (picking good sources), and again, supplementing  20 or 50mg is already gonna be huge.

 

 

Also while I'm think of it, lithium (spring water or orotate tabs) and melatonin (food sources) are mitochondria-friendly:

Effects of lithium on age-related decline in mitochondrial turnover and function in Caenorhabditis elegans.
Lithium-induced enhancement of mitochondrial oxidative phosphorylation in human brain tissue.
Melatonin in Mitochondrial Dysfunction and Related Disorders.
Melatonin and mitochondrial function.

Edited by gamesguru, 04 September 2015 - 03:11 PM.

[normalizing]

about berberine, i have never heard anyone switching from metformin to berberine with positive effect. also i have never seen anyone ever use berberine for any of the shitload of positive things it might bring  and actually have any good reports on this forum! I have been on here for quite long time checking on any good log of people actually using it and reporting positive experiences and NOTHING.

all in all, extremely overrated and until someone actually starts using it for REAL and not just recomend it all the time to people left and right without personal experience, i just think its a bunch of shit.

Edited by normalizing, 05 September 2015 - 10:09 AM.

[gamesguru]

I used it [Goldenseal] alongside amoxicillin for a suspected bacterial infection.  It's good for a shitload of positive things brah

[Bateau]

about berberine, i have never heard anyone switching from metformin to berberine with positive effect. also i have never seen anyone ever use berberine for any of the shitload of positive things it might bring  and actually have any good reports on this forum! I have been on here for quite long time checking on any good log of people actually using it and reporting positive experiences and NOTHING.

all in all, extremely overrated and until someone actually starts using it for REAL and not just recomend it all the time to people left and right without personal experience, i just think its a bunch of shit.

 

Both my grandmother and I take it.

 

Cant say for myself, but it definitely decreased my grandmothers fasting blood sugar & HbA1c and kept her HDL, LDL & total cholesterol at very healthy levels after we took her off of statin therapy.

 

FWIW

Edited by Bateau, 05 September 2015 - 03:36 PM.

[umop 3pisdn]

CRON might be one of the best way to preserve long term health, including reducing the risk of dementia. Nootropics and nutritional supplements seem like something to do on top of a healthy lifestyle, and then you can be more selective about what other interventions might confer the most benefit and are worth the cost. If this is something that you're going to do for the rest of your life taking the longer view and a more sustained approach might be most appropriate.

Edited by umop 3pisdn, 05 September 2015 - 06:02 PM.

[plumper76]

This study showed it's not always that dismalhttp://www.medscape....warticle/591091

[Phlogiston]

Umop, what is CRON? I'm not familiar with the acronym.

 

[umop 3pisdn]

Calorie restriction with optimum nutrition, it seems to decrease the risk of basically any disease associated with ageing. We have a subforum about calorie restriction here.

 

http://www.longecity...ie-restriction/

[normalizing]

This study showed it's not always that dismalhttp://www.medscape....warticle/591091

 

this is locked!

[plumper76]

Sorry here is even more recent info agreeing with that study.http://www.alzcompend.info/?p=225

[Phlogiston]

Plumper:

 

Thanks for that link. Highly encouraging information.