Protocol for Restoration of Cognitive Func...
Fafner55 31 Dec 2022
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 50 downloads
Edited by Fafner55, 31 December 2022 - 01:35 PM.
Fafner55 31 Dec 2022
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 29 Jan 2023
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 29 Jan 2023
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 03 Feb 2023
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.
Fafner55 30 Sep 2023
Fafner55 - interesting protocol. Any updates?
Thanks
ambivalent 02 Oct 2023
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 02 Oct 2023
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 29 Jan 2024
Attached Files
Edited by Fafner55, 29 January 2024 - 06:24 PM.
Mind 29 Jan 2024
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.