Physionic talks about Rapamycin, Alzheimer’s and autophagy

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Frailty - A New and Early Predictor of Dementia?

Signs of frailty may signal future dementia more than a decade before cognitive symptoms occur, in new findings that may provide a potential opportunity to identify high-risk populations for targeted enrollment in clinical trials of dementia prevention and treatment.

Results of an international study assessing frailty trajectories showed frailty levels notably increased in the 4-9 years before dementia diagnosis. Even among study participants whose baseline frailty measurement was taken prior to that acceleration period, frailty was still positively associated with dementia risk, the investigators noted.

“We found that with every four to five additional health problems, there is on average a 40% higher risk of developing dementia, while the risk is lower for people who are more physically fit,” study investigator David Ward, PhD, of the Centre for Health Services Research, The University of Queensland, Brisbane, Australia, told Medscape Medical News.

https://www.medscape.com/viewarticle/new-and-early-predictor-future-dementia-2024a1000kuc

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In Older People, Why Does a History of Oral Herpes Double the Risk of Dementia?

A 2024 study reported that an HSV infection may be indicative of doubled dementia risk in the older population (specifically, the participants included over 1,000 70-year-olds). The study found that people with antibodies for HSV-1 had a significantly higher risk of developing dementia. Specifically, being seropositive, or having antibodies in one’s blood, for HSV-1 nearly doubled the risk of dementia and Alzheimer’s disease.

Another study breaks it down this way: “Herpes simplex virus 1 (HSV1) is a neuroinvasive virus capable of entering the brain which makes it a candidate pathogen for increasing risk of dementia.” The virus can actually change the brain in a way that makes it susceptible to developing dementia.

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No HSV vax yet but many labs are working on it :pray:

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Want to minimize the risk of dementia? Take your cholesterol and blood pressure medications:

Use of common cardiovascular disease drugs and risk of dementia: A case–control study in Swedish national register data

Highlights

  • Use ≥ 5 years of common cardiovascular drugs was associated with lower dementia risk.
  • Common cardiovascular drug combination use was associated with lower dementia risk.
  • Anti-platelet use of any duration was associated with higher dementia risk.

https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.14389

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Deborah,
I would consider a couple things (I know nothing about rapa).

Read this. There are lots of studies showing the PUFAs are tied to Alzheimer’s. (corn oil, soy oil, canola, etc.)

See also:
https://lowtoxinforum.com/search/2106692/?q=pufa+alzheimer’s&o=relevance

This is also relevant (you body must be able to burn glucose):
https://raypeatforum.com/community/threads/delirium-and-dementia-ad-is-caused-by-inability-to-oxidize-glucose.17386/

Aspirin (here is just one post):
https://raypeatforum.com/community/threads/salicylate-for-alzheimers-aspirin.7880/

Lithium:

Many many articles on lithium and AD.
I take 5 mg a day of Lithium Orotate (Piping rock).

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  • Physical activity of any kind appears to increase a person’s cognitive processing speed, according to a new study.
  • While it is generally accepted that moderate-to-vigorous exercise benefits brain health, this study finds that any physical activity at all carries with it some cognitive benefit.
  • The study leveraged mobile phones to allow researchers to survey study participants regarding their activity levels nearly in realtime, and to test their cognitive processing speed multiple times during the day.
  • The positive effect of being active may have to do with a heightened sense of alertness that comes with physical movement.

Everyday physical activity offers a boost in short-term brain processing speed, according to the findings of a new study from researchers at Penn State College of Medicine.

The study found that common day-to-day activities, regardless of intensity, can provide a short-term improvement in mental reaction time similar to reducing one’s cognitive age by four years.

Previous research has established the value of moderate-to-vigorous physical activity for maintaining cognitive health — and for good health in general.

This study — published in Annals of Behavioral Medicine — uniquely investigates the potential benefit of activities in which people commonly engage during the course of their day, both at work and at home.

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Feeling lonely increased risk for all-cause #dementia by 31% and cognitive impairment by 15% (free gift article) https://wapo.st/3YOEthc

2 in 5 U.S. adults are likely to develop some form of #dementia after age 55, study finds (free gift article) https://wapo.st/3Wkxyfd

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An international team of scientists led by UdeM wife-and-husband team Zdenka Pausova and Tomas Paus links the presence of white spots on MRI brain scans of older adults to a genetic risk of dementia.

全文:

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Athletes Exhibit Better Working Memory than Sedentary People

A fair sized body of evidence shows that physical activity improves memory function, both in the short term immediately following exercise, and over the long term for people engaging in regular exercise. This occurs in both younger and older people; it isn’t just a matter of compensating for the effects of aging. The brain operates at the edge of its capacity, and delivery of greater nutrients and oxygen via increased cerebral blood flow following exercise enables greater activity. Thus it isn’t surprising to see associations between memory function and the level of physical activity required to be an athlete. Of note, this study isn’t all that great for older demographics - older athletes are relatively small in number.

This meta-analysis investigated the differences in working memory (WM) performance between athletes and non-athletes in non-sports-specific tasks. A comprehensive evaluation of 21 studies encompassing different age groups, genders, and sports types identified a small but statistically significant advantage in WM accuracy or capacity for athletes compared to non-athletes. Notably, this advantage was more pronounced when athletes were contrasted with a sedentary population.

We conducted seven subgroup analyses as part of this study. An age-specific investigation revealed a small but significant advantage in WM for young adult athletes over non-athletes. However, our investigation into the link between sports expertise and WM across various age groups is limited by a lack of substantial research focusing on older adults and children. Therefore, we are unable to confirm whether older athletes exhibit superior WM enhancement in comparison to other demographic groups. Considering the benefits of exercise for mitigating age-related cognitive decline, as well as its role in improving cognitive and learning abilities during childhood and adolescence, studies focusing on these age groups would be important. In particular, studies on older adults who are ex-athletes could provide insights into the long-term effects of sports.

Subgroup analysis based on sports types revealed that athletes from individual sports outperformed non-athletes in experimental WM tasks, while athletes from team sports showed no such significant advantage. Contrary to our expectations, no significant difference was found between individual and team sports subgroups in WM performance. These results suggest that the cognitive gains afforded by engaging in sports likely arise from general physiological and psychological effects.

Our comparison of WM performance of elite and non-elite athletes with that of non-athletes identified a WM advantage for elite athletes, while the advantage for non-elite athletes approached but did not reach statistical significance. Additionally, there was no significant difference in WM performance between the two subgroups. This finding prompts introspection regarding the sports performance-cognition nexus. Our results imply that cognitive benefits, particularly with respect to WM, stem more from sustained engagement in workout than from the high competitive level achieved.

The WM advantage observed in athletes in comparison to non-athletes is likely based on both physiological and psychological mechanisms. Physiologically, sports confer efficiency advantages in information processing and cognitive function by increasing cerebral blood flow, triggering the release of brain-derived neurotrophic factor, and promoting neural network plasticity. Psychologically, sports confer benefits that optimise cognitive performance through improved control, enhanced attention allocation, and accelerated information processing.

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Exercise is undoubtedly number one in prevention (or have lucky genes)

Keywords: donepezil, galantamine, memantine, rivastigmine, sodium oligomannate

There is no drug or supplement that I can find that has any proof of delaying or reversing Alzheimer’s or dementia. However, every one of the above drugs helps with age-related cognitive decline.

I take donepezil/memantine and galantamine.
Subjectively, they work great in clearing brain fog and helping short-term memory.
The donepezil/memantine took a week or two to really feel the effect.
Galantamine works immediately if you take 8 mg or more.
Galantamine has several nootropic and synergistic properties.

I definitely would not recommend donepezil/memantine to younger people.

Galatamine: Read some of the threads mentioning galantamine.

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Components of ashwagandha did show the unique ability to halt dementia in a mouse model and even promote reconstruction of the damaged neuronal networks themselves, effectively reversing the condition. It’s unknown whether it would similarly benefit humans with Alzheimer’s.

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Since humans have taken ashwagandha for millennia, I think any benefits for Alzheimer’s would have been noticed. “The history of its use in traditional Indian medicine dates back nearly 3000 years.”

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But with all that has been said… what if it is the immune system that causes Alzheimer’s and what better to help the immune system than rapamycin.

Rapamycin is an immune modulator it improves the immune system against flu, allergies, inflamm-aging.

Here’s a link: Alzheimer’s may not actually be a "brain disease" - Earth.com

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Look up intranasal rifampicin. Also klotho seems to be protective but obviously not at the clinical stage yet so high uncertainty re: dosing.

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More reasons to lose any visceral fat we have…

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Ketone Bodies Clear Damaged Proteins in the Brain

New research reveals that ketone bodies, beyond their role in energy production, are crucial in maintaining brain health by regulating protein quality control.

Ketone bodies, such as β-hydroxybutyrate, interact directly with misfolded proteins, making them insoluble and aiding in their clearance via autophagy.

This process helps prevent protein aggregation, which is linked to aging and neurodegenerative diseases like Alzheimer’s.

Animal studies demonstrated that increasing ketone levels through diet or supplementation reduces protein buildup in the brain and restores cellular function.

The findings connect metabolism with proteome health, offering new avenues for treatments targeting brain aging and diseases.

Researchers are now exploring how ketone-based therapies can be applied beyond the brain, including the gut and other systems.

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BTW does anybody know what the minimum to target is? Are there any downside to 0 if that’s even possible?
Thanks to low carbs and running, my latest DEXA says my visceral fat is 190g (6.7 oz) which is probably OK but there is still room for improvement if the target is 0.

BTW that also puts me all the time in mild ketosis so the following is another good news:

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Source article for a deep dive:

https://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(24)00459-8

This is why I’d put ketogenic diet in my bullet list of promising interventions for Alzheimer’s but truly it could be ketone esters alone.

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