Predicting Alzheimers & Dementia (and minimizing risk)

[RapAdmin]

Anti-inflammatory diet could lower your odds for dementia

[AnUser]

Or you can just take some anti-inflammatory drugs that are pretty safe and good.

[RapAdmin]

Stanford Reverses Cognitive Decline in Alzheimer’s With Brain Metabolism Drug

IDO1 inhibitors

IDO1 (indoleamine 2,3-dioxygenase 1) inhibitors are a class of drugs being investigated for their potential to modulate immune responses, particularly in the context of cancer and autoimmune diseases. Some of the notable IDO1 inhibitors that have been identified and studied include:

1. Epacadostat (INCB024360): Developed by Incyte Corporation, epacadostat has been one of the most well-known IDO1 inhibitors, though its development has seen ups and downs, including clinical trials with mixed results.
2. Indoximod: This compound is being investigated for its ability to inhibit IDO1 and has been studied in various cancer trials.
3. Navoximod (GDC-0919): Developed by Genentech/Roche, navoximod is another IDO1 inhibitor that has been evaluated in clinical trials for its efficacy in cancer treatment.
4. Kynic: This IDO1 inhibitor is in preclinical development and aims to address the IDO1 pathway to enhance immune responses against cancer.

These drugs target IDO1 to potentially enhance the immune system’s ability to fight tumors or manage autoimmune conditions. The effectiveness and safety of these inhibitors continue to be evaluated in clinical trials.

(ChatGPT)

[adssx]

In mice!

What I find more interesting is this:

Neuroscientists believe one of the key mechanisms by which Alzheimer’s disease impairs brain function is through the disruption of glucose metabolism, which is essential for energizing a healthy brain. Essentially, a decrease in metabolism deprives the brain of vital energy, thereby hindering cognitive functions and memory.

GLP-1RAs seem to restore glycolysis, so they’re quite interesting.

[RapAdmin]

Antidiabetic drugs show promise in reducing dementia risk

[adssx]

I think I posted this study before. What’s especially concerning for acarbose users is: “Metformin displayed the lowest risk of dementia across diverse antidiabetics, whereas α-glucosidase inhibitors demonstrated the highest risk.”

[EDIT: here was the previous discussion about this paper: Acarbose with food extends mice lifespan, does Acarbose "without" food also extend mice lifespan? - #47 by adssx ]

Also: it looks like they didn’t analyze GLP-1RAs.

[adssx]

Just published on the same topic: Repurposing antidiabetic drugs for Alzheimer’s disease: A review of preclinical and clinical evidence and overcoming challenges

Antidiabetic drug classes, notably GLP-1 analogs and SGLT2 inhibitors, and a reduced risk of dementia in patients with diabetes mellitus. […] On the other hand, alpha-glucosidase inhibitors (AGIs) and sulfonylureas may potentially increase the risk, especially in those experiencing recurrent hypoglycemic events.

Another paper highlighting the risk of alpha-glucosidase inhibitors (aka acarbose) for Alzheimer’s disease…

[ng0rge]

@adssx

Just published on the same topic: Repurposing antidiabetic drugs for Alzheimer’s disease: A review of preclinical and clinical evidence and overcoming challenges

Are you sure that’s the right link? That appears to go to - Effect of SGLT-2 inhibitors on arrhythmia events. All about A-Fib, nothing about Alzheimer’s or dementia.

[adssx]

Oops sorry, fixed. Thanks.

[DeStrider]

NMN may protect against Alzheimers

Therapeutic effect of nicotinamide mononucleotide on Alzheimer’s disease through activating autophagy and anti-oxidative stress

http://www.sciencedirect.com/science/article/pii/S0753332224010837

[adssx]

From the great “Research Center for Modernization of Characteristic Chinese Medicine, and Key Laboratory of Ningxia Ethnomedicine Modernization”

[DeStrider]

I’m just putting it out there, but, yes it is a low grade paper.

[ng0rge]

@DeStrider

yes it is a low grade paper

Are you saying that just because it’s from China? It says from Ningxia Medical University and funded by National Natural Science Foundation of China. Does that automatically mean “bad science”? Or “suspect”? Why?

[AnUser]

Ultimately, the journal and the country where a paper is from doesn’t matter. I think it’s funny to remark on MDPI, the pattern publications in that journal follows. But I should start reading MDPI papers as I dislike this bias more.

Papers can be bad but not because of who published it or where, or in which journal.

[adssx]

Most papers are incorrect or even fraudulent. The % of garbage is higher in some countries such as China, Iran, and Egypt. And then in each of these countries there are differences as well. If it’s from Peking University that’s probably okay. If it’s from an “Ethnomedicine” research group in a shitty uni in… Ningxia then it can probably go to the trash.

[ng0rge]

@RapAdmin

Stanford Reverses Cognitive Decline in Alzheimer’s With Brain Metabolism Drug

Just a follow-up on this.

Neuroscientists believe one of the key mechanisms by which Alzheimer’s disease impairs brain function is through the disruption of glucose metabolism, which is essential for energizing a healthy brain. Essentially, a decrease in metabolism deprives the brain of vital energy, thereby hindering cognitive functions and memory.

In the brain, kynurenine regulates production of the energy molecule lactate, which nourishes the brain’s neurons and helps maintain healthy synapses. Andreasson and her fellow researchers specifically looked at the enzyme indoleamine-2,3-dioxygenase 1 — or IDO1, for short — which generates kynurenine. Their hypothesis was that increases in IDO1 and kynurenine triggered by accumulation of amyloid and tau proteins would disrupt healthy brain metabolism and lead to cognitive decline.

“The kynurenine pathway is over activated in astrocytes, a critical cell type that metabolically supports neurons. When this happens, astrocytes cannot produce enough lactate as an energy source for neurons, and this disrupts healthy brain metabolism and harms synapses” Andreasson said. Blocking production of kynurenine by blocking IDO1 restores the ability of astrocytes to nourish neurons with lactate.

The next step is to test IDO1 inhibitors in human Alzheimer’s patients to see if they show similar improvements in cognition and memory.

And here is the paper:

https://www.science.org/doi/10.1126/science.abm6131

This makes me wonder…what if you could improve this pathway/process? Improve glucose metabolism to provide more energy to a healthy brain. Would that improve cognitive functions and memory?

Another new article on the IDO1 inhibitor study from one of the authors.

https://theconversation.com/what-links-aging-and-disease-a-growing-body-of-research-says-its-a-faulty-metabolism-236047

[ng0rge]

@adssx

“Ethnomedicine” research group in a shitty uni in… Ningxia

My question is why do you say that? My search for “ethnomedicine” shows nothing in the study. Some studies could be good? Are you basing it just on location? Beijing vs Ningxia? Size of the University? Do you know details of the departments?

[adssx]

“Ethnomedicine” and “Chinese medicine” are in the author affiliation. These are red flags for BS. And yes Ningxia was one of the poorest Chinese provinces. It’s now average in terms of GDP per capita, just thanks to their wine industry (which is quite funny given that Ningxia is a Muslim autonomous province). So the most cutting edge serious research will most likely not come out of Ningxia

[DeStrider]

There is a discussion thread that talks about Chinese and Russian paper mills that turn out made up findings in research journals. The rate for these two countries as well as some others is a 50% fraudulent rate. For US and Western papers, it is about 10%.

So, I won’t trust papers from a country where 50% of the research is known to be faked.

"Fake" Research Papers out of China, in Aging Field

I found this article interesting, and while its not specific to the aging research (Geroscience) field, it seems relevant as I’ve noticed increasing numbers of the paper I see in the aging field are coming out of China. I also wonder about the quality of the research papers in the geroscience field coming out of Russia, given that the entire country seems to be very corrupt. China’s fake science industry: how ‘paper mills’ threaten progress The country has become a prolific producer of academic research but fraudulent studies risk serious real-world consequences … “To survive in Chinese academia, we have many KPIs [key performance indicators] to hit. So when we publish, we focus on quantity over quality,” says a physics lecturer from a prominent Beijing university. “When prospective employers look at our CVs, it is much easier for them to judge the quantity of our output over the quality of the research,” he adds. The world’s scientific publishers are becoming increasingly alarme…

[ng0rge]

@DeStrider

So, I won’t trust papers from a country where 50% of the research is known to be faked.

OK, but that means that you are passing over the 50% that is legitimate and some of those may be very valuable studies or research trials that haven’t been duplicated elsewhere (yet). I think @adssx ,at least, is using some additional indicators and I would guess that people who know Chinese researchers and facilities could tell you with even more certainty. Isn’t there a resource for this - rating Chinese research? It can’t be a black box.