do ozempic and GLP-1s reduce APOE4 brain fog?

[nunchers]

Hi, I'm a thin athletic 45 year old male who is APOE4/4. I posted here the other day about starting to track my p-tau and trying to lower it.

Since I had my blood taken for my first p-tau test about two weeks ago, I started taking oral semaglutide (RYBELSUS) that I order from IndiaMart. This is a GLP-1 drug and is the same medicine as ozempic / wegovy, which are injections. I might switch to the injection at some point.

Semaglutide is being studied in Phase 3 for alzheimer's and it seems extremely likely to be effective for individuals with diabetes or obesity. The big question mark is how effective and whether it will also be effective in 'normal weight' people. Hopefully we will find out in 2025 when the study ends.

I'm not taking 7mg a day of Rybelsus (half a 14mg pill), which is a fairly low dose, but I'm ramping up. At first it was giving me a lot of stomach tightness but thats faded and I don't have other side effects from it.

I've been noticing that I feel more clear headed, which is most obvious to me when I wake up in the middle of the night or if I eat too much carbs. My whole life I've felt very shitty if I take a deep nap and wake up or am awoken in the middle of the night. I've always wondered if this was an APOE4/4 problem.

So.... I googled this and it seems that other people also feel less brain fog.

Here's a reddit thread of people talking about this:


Since alzheimers disease is often called 'Type 3 diabetes', I'm wonder if the GLP-1 is improving my brain metabolism and regulating insulin there.

Ironically, while I don't feel very hungry during the day, I think I'm actually eating as much or more than usual when I do eat. Part of that is because I consciously don't want to lose weight but also I've noticed that I don't feel as crappy when I have a lot of sugar / carbs. Not that I want to eat more sugar or carbs! But last night, for example, I didn't eat much during the day and then ate almost all of a large pizza, which I almost never do, and I didn't get that kind of brain fog / carb crash that I normally would.

Here's what GPT-4o says:

"Several studies have shown that individuals with the APOE4/4 genotype exhibit dysregulated brain insulin signaling, which is a significant factor in Alzheimer's disease (AD) pathogenesis.

Impaired Insulin Signaling: Research indicates that APOE4 impairs neuronal insulin signaling by binding to the insulin receptor, accelerating its aggregation, and preventing its proper trafficking. This leads to insulin resistance in the brain, which is a hallmark of Alzheimer's disease in APOE4 carriers​ (BioMed Central)​​ (Alzforum)​.

Cerebral Glucose Dysregulation: Studies have found that APOE4 carriers show reduced expression of insulin signaling proteins such as IRS1 and Akt, which are critical for insulin signaling pathways. Additionally, brain glucose metabolism is significantly affected in these individuals, with evidence pointing to lower glucose uptake and utilization in the brain​ (BioMed Central)​​ (Frontiers)​.

Clinical Correlations: Clinical trials involving intranasal insulin administration have shown cognitive improvements in Alzheimer's patients, particularly in those with the APOE4 genotype. This suggests that targeting insulin signaling pathways may be beneficial for APOE4 carriers​ (BioMed Central)​.

Molecular Mechanisms: APOE4 has been shown to bind more strongly to amyloid-beta (Aβ), exacerbating the toxic effects of Aβ on insulin signaling. This interaction further impairs glucose metabolism and insulin sensitivity in the brain, contributing to the neurodegenerative processes seen in Alzheimer's disease​ (Alzforum)​."

Anyway, I was wondering if anyone else on this forum has taken a GLP-1 drug like Ozempic or Mounjaro, and if you have noticed any change in your cognition or clarity.

Thanks!

[Annadfrances]

I have also been wondering about this. My understanding is that it’s VERY tricky to put anyone on these drugs without significant margin for weight loss (30-40lbs headroom). So those of us who are 4/4, high cholesterol, but very lean are likely only candidates for extremely low doses (subclinical). If this medication has the ability to maintain insulin sensitivity in tissue that is genetically predisposed to lose it, it would be worth finding ways to maintain weight while on it.

[nurse_mel]

Hi, I'm a thin athletic 45 year old male who is APOE4/4. I posted here the other day about starting to track my p-tau and trying to lower it.

Since I had my blood taken for my first p-tau test about two weeks ago, I started taking oral semaglutide (RYBELSUS) that I order from IndiaMart. This is a GLP-1 drug and is the same medicine as ozempic / wegovy, which are injections. I might switch to the injection at some point.

Semaglutide is being studied in Phase 3 for alzheimer's and it seems extremely likely to be effective for individuals with diabetes or obesity. The big question mark is how effective and whether it will also be effective in 'normal weight' people. Hopefully we will find out in 2025 when the study ends.

I'm not taking 7mg a day of Rybelsus (half a 14mg pill), which is a fairly low dose, but I'm ramping up. At first it was giving me a lot of stomach tightness but thats faded and I don't have other side effects from it.

I've been noticing that I feel more clear headed, which is most obvious to me when I wake up in the middle of the night or if I eat too much carbs. My whole life I've felt very shitty if I take a deep nap and wake up or am awoken in the middle of the night. I've always wondered if this was an APOE4/4 problem.

So.... I googled this and it seems that other people also feel less brain fog.

Here's a reddit thread of people talking about this:


Since alzheimers disease is often called 'Type 3 diabetes', I'm wonder if the GLP-1 is improving my brain metabolism and regulating insulin there.

Ironically, while I don't feel very hungry during the day, I think I'm actually eating as much or more than usual when I do eat. Part of that is because I consciously don't want to lose weight but also I've noticed that I don't feel as crappy when I have a lot of sugar / carbs. Not that I want to eat more sugar or carbs! But last night, for example, I didn't eat much during the day and then ate almost all of a large pizza, which I almost never do, and I didn't get that kind of brain fog / carb crash that I normally would.

Here's what GPT-4o says:

"Several studies have shown that individuals with the APOE4/4 genotype exhibit dysregulated brain insulin signaling, which is a significant factor in Alzheimer's disease (AD) pathogenesis.

Impaired Insulin Signaling: Research indicates that APOE4 impairs neuronal insulin signaling by binding to the insulin receptor, accelerating its aggregation, and preventing its proper trafficking. This leads to insulin resistance in the brain, which is a hallmark of Alzheimer's disease in APOE4 carriers​ (BioMed Central)​​ (Alzforum)​.

Cerebral Glucose Dysregulation: Studies have found that APOE4 carriers show reduced expression of insulin signaling proteins such as IRS1 and Akt, which are critical for insulin signaling pathways. Additionally, brain glucose metabolism is significantly affected in these individuals, with evidence pointing to lower glucose uptake and utilization in the brain​ (BioMed Central)​​ (Frontiers)​.

Clinical Correlations: Clinical trials involving intranasal insulin administration have shown cognitive improvements in Alzheimer's patients, particularly in those with the APOE4 genotype. This suggests that targeting insulin signaling pathways may be beneficial for APOE4 carriers​ (BioMed Central)​.

Molecular Mechanisms: APOE4 has been shown to bind more strongly to amyloid-beta (Aβ), exacerbating the toxic effects of Aβ on insulin signaling. This interaction further impairs glucose metabolism and insulin sensitivity in the brain, contributing to the neurodegenerative processes seen in Alzheimer's disease​ (Alzforum)​."

Anyway, I was wondering if anyone else on this forum has taken a GLP-1 drug like Ozempic or Mounjaro, and if you have noticed any change in your cognition or clarity.

Thanks!

Dr. Tyna Moore has several podcasts out on microdosing GLP-1s in already thin people to enhance metabolism, etc.

[nunchers]

Dr. Tyna Moore has several podcasts out on microdosing GLP-1s in already thin people to enhance metabolism, etc.

Super interesting- thanks! I'll check it out.

Here's a new discord group for people tracking tau:
https://discord.gg/SCYaBrNFZM

[Orangeblossom]

On this subject this was in the news this week in the UK as helping cognition in dementia.

https://www.theguardian.com/society/art ... %20a%20day.

[Brian4]

Here's a new discord group for people tracking tau: https://discord.gg/8uJdfpj8

I'm getting an "invalid invite" warning on this. (I confess Discord baffles me, and maybe I'm doing something wrong.)

[Brian4]

Since I had my blood taken for my first p-tau test about two weeks ago, I started taking oral semaglutide (RYBELSUS) that I order from IndiaMart.

Could you let us know which vendor you used? I've been ripped off too many times at IndiaMart to want to pick one on my own. Thanks! Brian

[nunchers]

I actually switched to getting tirzepatide from tryeden, I said I was very heavy even though im not. I highly recommend getting an injectable vs rybelsus, way less side effects. there's lots of compounding services. some offer same prize for any dose so I said I was on a high dose already and I just take a small fraction of that and it lasts a very long time so it's not too expensive.

this is the India mart vendor I used if you still want that. they are great:

https://www.indiamart.com/forveda-onlin ... onial.html

and I assume everyone saw the recent news that GLP-1s do appear to reduce Alzheimer's decline! semaglutide or tirzepatide are much stronger than the older version they studied and should have an even better brain effect.

[CAngelS]

I actually switched to getting tirzepatide from tryeden, I said I was very heavy even though im not. I highly recommend getting an injectable vs rybelsus, way less side effects. there's lots of compounding services. some offer same prize for any dose so I said I was on a high dose already and I just take a small fraction of that and it lasts a very long time so it's not too expensive.

this is the India mart vendor I used if you still want that. they are great:

https://www.indiamart.com/forveda-onlin ... onial.html

and I assume everyone saw the recent news that GLP-1s do appear to reduce Alzheimer's decline! semaglutide or tirzepatide are much stronger than the older version they studied and should have an even better brain effect.

This is interesting. How does this work? I'm unfamiliar with ordering from India.

Do you have the drug compounded here in the US? Or is it compounded for you before shipping?

[nunchers]

If you use a service like tryeden or Ro or hims or one of many others, they send you a bottle and needles and you inject yourself. very simple.