haidut

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I touched upon this topic in one of the Danny Roddy shows we did last year but the evidence since then has continues to accumulate that AD is entirely a metabolic disorders, basically identical to diabetes but focusing on the brain. A recent study found that delirium, an acute form of dementia/AD, is due to inability to metabolize glucose.
Delirium (and Dementia/AD) Is Caused By Inability To Oxidize Glucose
This new study found out that the reason drugs like the adamantane derivative memantine help treat AD is not only due to their NMDA and cholinergic antagonist but because they improve insulin sensitivity, especially in the brain.
Another potent inhibitor of the same potassium channel is DHEA, which has been shown to be increased in the brains of patients with AD. Ray wrote once that he was wary of recommending DHEA due to that link between it and AD but now it looks like the accumulation of DHEA in AD is adaptive/protective. So, small doses of DHEA, especially combined with pregnenolone (which also improved insulin sensitivity) may be an alternative to drugs like memantine. Thyroid, aspirin, niacinamide, cyproheptadine, lisuride, bromocriptine, magnesium, taurine, etc all have potent insulin-sensitizing properties and unsurprisingly have also shown benefit in treating AD.

https://www.nature.com/mp/journal/vaop/ncurrent/full/mp2016187a.html
Alzheimer's disease found to be a diabetic disorder of the brain

"...Researchers at Tohoku University have found a promising treatment for Alzheimer's disease, by noticing a similarity in the way insulin signaling works in the brain and in the pancreas of diabetic patients." "In the pancreas, the Kir6.2 channel blockade increases the insulin signaling, and insulin signaling decreases the blood glucose levels," says Dr. Shigeki Moriguchi. "In the brain, insulin signaling increases the acquisition of memory through CaM kinase II activation by Kir6.2 channel blockade." The research group, led by Dr. Moriguchi and Professor Kohji Fukunaga of the Graduate School of Pharmaceutical Sciences, thus concluded that Alzheimer's disease can be described as a diabetic disorder of the brain."

"...Memantine, a drug widely used to treat Alzheimer's disease, is a well known inhibitor of the N-methyl-D-aspartate (NMDA) receptors that prevent excessive glutamate transmission in the brain. Researchers have now found that memantine also inhibits the ATP-sensitive potassium channel (Kir6.2 channel), improving insulin signal dysfunction in the brain."

"Since KATP channels Kir6.1 or Kir6.2 are critical components of sulfonylurea receptors (SURs) which is downstream insulin receptor signaling, the KATP channel inhibition by Memantine mediates the anti-diabetic drug action in peripheral tissues," says Dr. Moriguchi. "And this leads to improved cognitive functions and improved memory retention among Alzheimer's patients." The researchers now hope that results of their study and the parallels drawn with diabetes, will lead to new treatments for Alzheimer's disease, using the inhibition of Kir6.2 channel."
 

Luann

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Well done. Diabetes of the brain. I've thought along the lines of that before, mostly about violent or anti-social behavior given the links you can see between those and glucose metabolism.

Incredible how simple AD really is.
 

Gibson2k3

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So wouldn't intra nasal insulin spray be useful in slowing down this disease or perhaps preventing it?
 

jondoeuk

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So wouldn't intra nasal insulin spray be useful in slowing down this disease or perhaps preventing it?

Back in 2012 one trial involved 104 cognitively impaired patients with either MCI or AD. Subjects were assigned to on of three arms (20 iu insulin daily; 40 iu insulin daily or placebo daily for 4 months), intranasal insulin improved delayed memory (in the 20 IU group) and preserved caregiver-rated functional ability (both groups) Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment Some of these results were later confirmed in a smaller trial last year Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer’s Disease Biomarkers: A Pilot Clinical Trial - IOS Press

However, none of this has been confirmed in any PhIII I know of. In the mean time it would be nice to see combo trials using intranasal insulin with other drugs to reduce the likelihood of resistance https://www.alzheimersanddementia.com/article/S1552-5260(13)02921-X/fulltext
 

GAF

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My gf and I are trying the above and having excellent results. You can really just walk up to the counter at WM and buy it for $24.88. Amazing.
 
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High_Prob

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Repurposing Diabetes Drugs for Brain Insulin Resistance in Alzheimer Disease

'One approach is to overcome brain insulin resistance with exogenous insulin, but a theoretical concern of this approach is that in the long-run the chronic hyperinsulinemic environment will actually perpetuate brain insulin resistance.

One theoretical concern about intranasal insulin is that chronic hyperinsulinemic conditions in the brain may actually promote brain insulin resistance. For example, excessive exposure to insulin in mice leads to phosphorylation of key components of the insulin cascade, such as AKT, GSK-3β, and p70S6K, consistent with insulin resistance (14).'
 

GAF

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but a theoretical concern of this approach is that in the long-run the chronic hyperinsulinemic environment will actually perpetuate brain insulin resistance.

Who would want to create a chronic HYPER whatever environment of anything anywhere? These guys should be looking for how to deliver the tiniest effective dose anyway and not making fear mongering statements about doing something no one would want to do. Why don't they actually do some science? We all know they won't be looking for some way to improve the dementia issue cheaply and effectively. AD individuals don't have a LONG RUN anyway!
 

GAF

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she is already scared of all this self experiments with drugs

These scaredy cat people just crack me up. I presume she is NOT scared of the herbacide, insecticide, pufacide food she eats that came in BPA/S saturated container blah blah blah. I would be sneaking a few drops of cypro into her latte every day trying to lower her serotonin so she can learn to be a crazy mad scientist like me. I wouldn't actually do that, but what I would do is help her find a new partner with malfunctioning thought processes similar to her own.

I think I read that one spray is 10IU. Is that a lot or is that a tiny amount? How much insulin is in the brain all the time anyway in a healthy young person? Anyone know?
 
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These scaredy cat people just crack me up. I presume she is NOT scared of the herbacide, insecticide, pufacide food she eats that came in BPA/S saturated container blah blah blah. I would be sneaking a few drops of cypro into her latte every day trying to lower her serotonin so she can learn to be a crazy mad scientist like me. I wouldn't actually do that, but what I would do is help her find a new partner with malfunctioning thought processes similar to her own.

I think I read that one spray is 10IU. Is that a lot or is that a tiny amount? How much insulin is in the brain all the time anyway in a healthy young person? Anyone know?

The problem is Im struggling with health issues since childhood and despite almost 100% peat my condition is far away from being solved. She is in a perfect condition despite of her age and crappy diet full of pufa. She does 3xweek jiu-jitsu, 2xweek gym, she is a massage therapist and we dont have a car. Makes me think sometimes that some people just born to thrive and others like me to suffer.
 

GAF

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Sounds to me like you are a lucky guy. You must have at least one big redeeming quality that attracts her to you. I hope you are keeping her laughing every day so she will keep you around.

Fortunately, our lives are not comparative experiences. We all get our own unique life experience. Whether it all evens out in the end is not our problem so no need to worry about that.

I am 62 so I guess a little boost from the intranasal insulin is not that surprising. If I was a lot younger, it would be pretty scary if the brain insulin resistance had already deteriorated. I think that makes this experiment a bit interesting. So, hopefully, some of the younger folks will give it a try and report their experiences. Meanwhile, my GF is soon to try it on her 83 yr old AD mom and I am going to try it on my 85 yr old not AD parents.

I sure wish I could get rid of our 3 cars. Just think of the crooks and thieves I could eliminate from my life every day - tax-collecting police officers and red-light cameras, auto insurance scammers, big oil frackers, car repair slime, bankers, not to mention the drunks and potheads and other idiots driving all around me everyday.
 
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