11 replies to this topic

[Fafner55]

The attached protocol is intended to clawback cognitive functions, such as slower perceptual speed and the ability to form new memories, that declines naturally in healthy aged individuals. It does not address disease models of cognitive impairment.

 

This protocol is largely absent of side effects, and for me at least it restored perceptual speed to that of an average 20-year-old college student. It is based on the hypothesis that in healthy individuals the age-associated decline in cognitive abilities is restored by repairing accumulated damage, reducing inhibitory factors and modulating the BDNF-TrkB signaling pathway.

 

There is a bigger picture in this protocol with regards to age-related health. A large part of the decline in cognitive function is traced back to decreased cellular fitness. Age-associated changes in cellular fitness is largely correctable by supplementation with glutathione precursors to reduce oxidative damage and by the soluble bile acid TUDCA. 

 

Those that have trouble accessing the attached protocol can download it from this link

Protocol for Restoration of Cognitive Function in Aged Individuals

 

Abstract 

Background/Aims

The healthy brain in aging humans is characterized by reduced perceptual speed and increased difficulty in acquiring new memories. The ability to form new neural networks and change through growth and reorganization is referred to as brain plasticity. Reduction in brain plasticity and cognitive function affects quality of life and may result in older individuals being downgraded in their jobs or dropping out of the workforce. The aim of this study is to create a protocol that restores measurable phenotypes of brain aging, such as perceptual speed, of healthy individuals over the age of 65 years to that of an average 20-year-old.

 

Methods

Age-associated changes in perceptual speed and memory formation in the hippocampus result from reduced growth and density of synaptic sprouts and dendritic spines. These features are largely affected by a single signaling pathway, BDNF-TrkB, with known inhibitors and agonists, and by more general measures of cellular fitness such as redox imbalances and dysregulated proteostasis. In this study, age-associated changes to the hippocampus are identified and the efficacy of small molecules that modulate those changes are assessed. Dosages are determined from self-tests. Trail Making Test A (TMT-A) is used to measure the effect on perceptual speed.

 

Results

For a 67-year-old subject, TMT-A was not available until 12 weeks into this study and an initial baseline was not established. Notwithstanding, published results for one treatment, glutathione precursors termed GlyNAC, showed an 18% improvement in TMT-A scores after 12 weeks [153]. After the first 12 weeks of this study, a TMT-A baseline was then established for the subsequent treatments (7,8-DHF, hesperidin, lion’s mane mushroom extract and TUDCA), which were found to give an additional 25% improvement. Together, the TMT-A time of a 67-year-old improved from 28 seconds (the 17th percentile of 20-year-old college students, measured after 12 weeks of treatment) to 21 seconds (the 55th percentile). Consistent with mouse studies, levels of anxiety and depression were reduced.

 

Conclusion

In healthy individuals, between the ages of 20 and 70 years perceptual speed slows on average by 76% as measured by TMT-A. By the age of 85, the decline is 138% [299]. This decline was completely abrogated in a 67-year-old by readily available supplements that modulate and restore age-associated changes to the BDNF-TrkB pathway, redox imbalances and dysregulated proteostasis.

 

Supporting Materials

Printable Trail Making Tests and a calculator for relating Trail Making Test scores to percentiles by age can be downloaded from Quantifying the results of this protocol - Trail Making Tests.

 

 Cognitive Function Restoration Protocol_2022-12-26a_f.pdf   14.94MB   52 downloads

 

Edited by Fafner55, 31 December 2022 - 01:35 PM.

[Fafner55]

For unknown reasons, I no longer receive notifications from Longecity.org. If I do not respond to postings or messages, it is because I am unaware of them.

[ambivalent]

A Validation ofyour work - GLYNAC clinical trial.

 

https://academic.oup...8639?login=true

 

Conclusion:

 

"This RCT provides evidence to show that GlyNAC supplementation in OA improves GSH deficiency, OxS, mitochondrial impairment, mitophagy, inflammation, insulin resistance, endothelial dysfunction, physical function and strength, exercise capacity, waist circumference, state systolic blood pressure, and multiple hallmarks of aging (mitochondrial dysfunction, altered intercellular communication, dysregulated nutrient sensing, loss of proteostasis, genomic toxicity, stem-cell exhaustion, and cellular senescence). GlyNAC supplementation begins to improve age-associated declines within 2-weeks but a longer duration of supplementation is needed for a greater magnitude of improvement. This RCT provides proof-of-concept that GlyNAC supplementation represents a novel, simple, safe, and effective nutritional approach in humans to promote and improve healthy aging.

 

 

 

[ambivalent]

Fafne55, do you have any estimate as to the likely improvement expected due to the practice effect over the period of your study on TMT-A scores?

[Fafner55]

Fafne55, do you have any estimate as to the likely improvement expected due to the practice effect over the period of your study on TMT-A scores?

 

I address that question in section "Quantifying the results of this protocol - Trail Making Tests" of the protocol. 

Learning affects TMT-A scores too. This effect can be compensated for by increasing score times by 16%, where the 16% is taken from a study of possible cognitive benefits of astaxanthin on 51-year-olds. That study used  a similar test of perceptual speed and found a 16% improvement in both the placebo and test groups [210].

[210] “Effects of astaxanthin-rich Haematococcus pluvialis extract on cognitive function: a randomised, double-blind, placebo-controlled study” (2012) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432818/

 

In my experience, one learns to keep one's hand raised to avoid covering numbers, and the eye is trained to take in more area when scanning for the next number. But, this training quickly reaches its limit. If one practices a bit, then a reproduceable baseline can be established. 

 

For consistent results, the times of 4 or more tests should be averaged after outliers are discarded. 

[MidwestGreg]

Fafner55 - interesting protocol. Any updates?

 

Thanks

[Fafner55]

Fafner55 - interesting protocol. Any updates?

 

Thanks

 

 

Since posting this protocol 10 months ago there are a few revisions I need to make.

 

The challenge has been to work out a protocol that can be taken over a long period of time. Hesperidin failed that test. Taken daily, hesperidin eventually led to brain fog and an unfocused mind, even at small doses. I still believe in the hypothesis that systemic inflammation is inhibitory to synaptic sprouts and dendritic spine growth, and I have a short list of phytosubstances that should help, but I haven't had time to systematically self-test them. In a year or so I should be able to update the protocol in that regard.

 

Supplements that I can report are effective and can be taken daily are

- GlyNAC 

- 7,8-DHF

- Lion's mane mushroom extract

 

I upped my dosage of 7,8-DHF from 25 mg/day in the morning to 25 mg followed by another 25 mg a few hours later. The benefits of 25 mg 7,8-DHF diminished over time and the additional 25 mg made it effective again. 

 

The effects of lion's mane mushroom extract are more subtle than 7,8-DHF. I increased my dosage of lion's mane from about 0.7-1.0 g/day to 1.0-1.5 g.

 

Currently I am in a full time grad student in cell biology and computational biology. This semester's genetics course involves a great deal of memorization. Without question, 7,8-DHF is helping me do well. I don't think I could pass this kind of demanding course without it.

 

By another measure of cognitive function, my average Trail Making Test A score remains in the 22 to 23 second range.

 

/Fafner55

[ambivalent]

Good to hear from you Ffaner. May I ask if you dropped tudca - Ihave been taking glynac and tudca quite regularly for a few months. Also where did you source the tropoflavin, it looks quite hard to get hold of (from the uk).

 

 

[Fafner55]

Good to hear from you Ffaner. May I ask if you dropped tudca - Ihave been taking glynac and tudca quite regularly for a few months. Also where did you source the tropoflavin, it looks quite hard to get hold of (from the uk).

 

TUDCA appears to be safe and without side effects. I still take it, but do not see a need to take it daily. After an initial cycle of 500 mg 2x/day for 3 months, I now take it for a month every 6 months or so to reduce ER stress and accumulated protein aggregates.

 

 

In the US, I have purchased tropoflavin (7,8-DHF) directly from Nootopics Depot and through Amazon. Nootopics Depot  or another US vendor might ship to the UK.

[Fafner55]

Version 2024-01-29a

Since posting the first version of this protocol 13 months ago a few  revisions were needed.

The challenge has been to work out a protocol that can be taken over a long period of time. Hesperidin failed that test. Taken daily, hesperidin eventually led to brain fog and an unfocused mind, even at small doses. Since systemic inflammation inhibits synaptic and dendritic spine growth, I self-tested various phytosubstances and settled on the flavone diosmetin, or rather its glycoside diosmin, as a substitute for hesperidin.

Another change to the protocol is an increase in  lion's mane mushroom extract from 0.7 g 1x/day to 1.0 g 2x/day. 

I continue to take GlyNAC supplementation daily. About 2x/year, I clear senescent cells with fisetin and grape seed extract, and reduce the accumulated burden of protein aggregates with TUDCA.

As for measurable benefits, my average Trail Making Test A score remains consistently in the 21 to 22 second range. Subjectively, I feel that the forgetfulness, the fog and the frustration I was experiencing are now in the past.

 

Printable Trail Making Tests and a calculator for relating Trail Making Test scores to percentiles by age can be downloaded from Quantifying the results of this protocol - Trail Making Tests.

A PDF copy of this protocol can be downloaded from Cognitive Function Restoration Protocol_2024-01-29a

 

/Fafner55

Attached Files

•  Cognitive Function Restoration Protocol_2024-01-29a.pdf   20.97MB   23 downloads

Edited by Fafner55, 29 January 2024 - 06:24 PM.

[Mind]

With oral supplements, I would tend to think the effect would wane over time. Initially, there might be cognitive benefits due to the previous lack of specific nutrients or from slight repair of damaged tissues. Over time, I would tend to think there would continue to be more damage from overall aging that would counteract those initial effects. Unless there is some sort-of systemic rejuvenation occurring, it seems long term benefits will be tough to come by.

 

However, I am glad to see your regimen is working. Any health/cognitive benefits one can accrue right now, even if they are minor, are better than nothing (or going in the wrong direction). Please keep us posted.

[Sikorsky]

Fafner55, your insights are incredibly valuable. Thank you for sharing them.

 

Please don't be discouraged by the low engagement from other users. Please keep posting whatever you find valuable.

 

I think you will find a lot of valuable ideas in this thread: https://www.longecit...iments-curated/