Protecting the Brain as We Age

As Rod Serling used to say, “For your consideration”:
Many of us older members of the forum are acutely aware of age-related mental decline.
We want to live longer, but only if our brain is still intact.

I recently read some news about galantamine (galantamine works by increasing the levels of acetylcholine, a neurotransmitter that is important for memory and cognitive function) and hadn’t realized the FDA approved it for the treatment of Alzheimer’s and dementia. “Galantamine is derived from a natural source, specifically from the bulbs and flowers of the daffodil plant (Narcissus sp.) and the leaves of the snowdrop plant (Galanthus sp.). Galantamine has been used for centuries in traditional medicine, and it was first isolated from the bulbs of the daffodil plant in the 1950s. The compound is also now synthesized in the laboratory.”

“The review reveals the protective effects of galantamine on the functions and integrity of the liver, brain and memory impairment. Various independent studies have shown anti-Alzheimer, antioxidant, antidiabetic and neuroprotective effect of galantamine.”

Of course like NAC it has been a little bit harder to find without a prescription.
It seems like the pharmaceutical industry wants to monetize any natural substance that actually works.

I bought some quite some time ago while experimenting with lucid dreaming. It works quite well if taken at the proper time. I soon found out that I was not particularly fond of lucid dreaming and my galantamine had been setting on the shelf. I have two kinds, tablets and liquid.
I think the liquid works better than the tablets as you can take it sublingually and it doesn’t taste bad. I have posted a link below.

Galantamine: A Review Update
http://jddtonline.info/index.php/jddt/article/view/5426/4788

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I think some extra melatonin at night is good for the brain.

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I will shamelessly be using;

"for your consideration”

Thank you

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I have been taking what I considered to be a high dose for several decades. But, based on your posts and a little research I upped my dose to 60 mg at night. Surprisingly to me, it produced no daytime drowsiness.

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Serious question: in the case of someone like @desertshores who is 80+ years old and obviously still mentally sharp/unaffected by dementia/etc, is cognitive decline ever likely to affect them?

I just read an interview with a 115-year-old woman, and she seemed to be just as sharp as I am at 45. I don’t think she’s taking any supplements or anything.

Once you hit a certain age and have no signs of mental decline, aren’t you probably “in the clear”?

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Timing is critical. You also need to consider a two compartment model where some melatonin is in the cerebral spinal fluid and turning over about 20% an hour and other melatonin is in the blood serum with a half life of around 30 mins. I think when the melatonin levels drop sufficiently in the blood it kicks off a Cortisol Awakening Response in the next ultradian cycle. That can make you quite awake as the magnitude of the CAR is linked to the movements in melatonin.

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For some younger members like me, we also don’t want to loss our cognitive functionality in later life, but it’s hard to imagine what the mental decline feels like.

Can you share your experience of what’s the feeling of age-related mental decline? Did it effect the short term memory, long term memory, reasoning ability, or creativity, or all of them? And when did it start, did the mental decline start at 30s, 40s, 50s, or 60s…?

To answer your question:

Unfortunately, as we age brain shrinkage occurs starting at around 40. This is inevitable and cannot at this time be stopped.

This rate is variable due to genetics, lifestyle, exercise, etc.
The best way to slow it down from articles I have read is physical and mental exercise.

The only noticeable defect that I subjectively feel is like that of a computer where you replace the microprocessor with one that is a little bit slower. Everything still works the same, but a little bit slower.

As far as I can tell my memory is totally intact. Who can tell? But, I am surprised at how much early memory I have retained compared to my nearest relatives. For instance: I recall crawling on the floor with my father and eating in a highchair. I have many memories of before the age of four

I have taken a boatload of supplements over the years. Maybe they have helped.

I don’t take a bunch of tests to determine my mental capacity, but I do use the NY Times crossword puzzles and sudoku solving as personal markers. I seem to have plateaued, but I have lost little or no ability to solve them. Maybe a little slower I don’t know, but it is not subjectively slower.

As far as I can tell, no supplements have been shown to stop or slow down brain shrinkage.
Maybe, rapamycin does. I hope so.

Fortunately, no one close on my family tree has suffered from Alzheimer’s or dementia.
My mother lived until 93 and worked on a farm for the first half of her life and loved bacon and ate tons of it. Her diet was largely meat, potatoes, milk, butter, and bread. Her mind was sharp up til the day she died. She did not smoke or drink. The point being, is she was helped greatly by genetics IMO.

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Replacing the microprocessor with one that is a little bit slower is really a vivid metaphor, thanks for sharing your experience, you give us a better imagination of the mindset of aging.

It’s lucky you have good kid memory, I can’t recall too much thing before 4, most of my childhood memories, which are mostly bad memories, maybe I will recall some of good childhood memories when I get older,

Some studies shows bilingualism may be a protective factor in preventing dementia, although it’s not very conclusive, it’s not a bad thing to learn a new language.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4353628/

https://sci-hub.ru/10.3758/s13423-020-01736-5

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why do you take so much ? Just curious, I mean melatonin shows effects in concentrations as little as 0.1mg for sleep.

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I track how much melatonin I take each night and the last week was 460, 130, 100, 350, 100, 50,
100 (figures in milligrams).

I have not yet taken over a gram, but I have taken over 0.9 of a gram.

I never take melatonin to get me to sleep.

I take melatonin for these reasons:
a) To extend sleep,
b) To get me back to sleep (handling middle insomnia)
c) To reduce gingivitis
d) To generally reduce inflammation
e) As an adjunct to mitochondrial melatonin
f) To improve the quality of sleep and improve cognitive function
g) As an anti-cancer prophylactic.

When I sleep really well and enough to not need melatonin to get back to sleep I take some to top up my pineal melatonin. It is generally forgotten that melatonin is at least to some extent and probably more than this injected into the CSF and not the serum.

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Probably more than you wanted to know:
As mentioned in another thread I do not use melatonin for sleep purposes.
This a self-experiment based on John Hemmings’s experience. He takes very high doses and is still alive :smile: and book I read a long time ago:
“Melatonin: Breakthrough Discoveries That Can Help You Combat Aging, Boost Your Immune System, Reduce Your Risk of Cancer and Heart Disease, Get a Better Night’s Sleep Paperback – July 1, 1996 by Russel J. Reiter (Author), Jo Robinson (Author)”
and on a recent Kindle book:
" Extreme Dose! Melatonin The Miracle Anti-Aging Hormone Anti-Alzheimer’s Hormone Anti-Baldness Hormone Menopause Reversal Hormone Kindle Edition"
These two books tend to be mostly anecdotal and are not based on good scientific studies.
That is why I say it’s a self-experiment.

There are more recent studies indicating the benefits and safety of high-dose melatonin.

“Beyond its sleep and chronobiotic properties, melatonin is a potent antioxidant9 and has the ability to cross the blood-brain barrier,10 with suggested anti-amyloid properties. Due to this, melatonin has been increasingly investigated in many varying conditions, including cancer, cardiometabolic conditions and neurodegenerative diseases at higher doses, where there is less documentation of its safety. Doses ranging from 30 to 100 mg are being suggested or tested for effectiveness in a range of conditions and ages”

“Based on this limited evidence, melatonin appears to have a good safety profile. Better safety reporting in future long-term trials is needed to confirm this as our confidence limits were very wide due to the paucity of suitable data.”

There is some evidence of high-dose melatonin improving insulin sensitivity, etc.
A recent meta-analysis concluded:

“Conclusions: Our results showed that melatonin supplementation was useful for reducing diabetes parameters when compared to placebo.”

“Melatonin is a potent natural antioxidant and anti-inflammatory agent that protects against toxic side effects of radiation and chemotherapy”

"Safety of higher doses of melatonin in adults: A systematic review and meta- analysis

https://onlinelibrary.wiley.com/doi/full/10.1111/jpi.12782

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The various reports on Melatonin are quite helpful. It really makes a difference, but it is not a complete solution.

I think I have a complete solution (or something close to this) now, but I do end up taking a lot of melatonin during the night and currently over 80 capsules of various supplements during the day as well as other things (including intermittent rapamycin) from time to time.

When I say a complete solution I think it improves healthspan, but I am not yet persuaded that it improves lifespan in a material manner. (as in being more healthy will make you live a bit longer, but the max probably won’t shift).

"For your consideration” (yes, I am shamelessly using this line.

Research Hot Spots and Trends on Melatonin From 2000 to 2019

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669723/#:~:text=Contributions%20of%20Authors%20to%20Melatonin%20Research&text=Russel%20J%20Reiter%20(638)%20was,121)%20(%20Table%203%20).

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Good find. “To our surprise, the results also indicated that melatonin has the potential to treat osteoporosis” Didn’t catch that one before.

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" I am not yet persuaded that it improves lifespan in a material manner"
As far as I am aware there is nothing that has been proven to extend lifespan in humans, only healthspan.

FWIW

Russel Reiter, the world’s leading researcher melatonin.

And I am not meaning his general consumer book published in the mid 90.

He is around 88, take/taking 180mg{yes 180mg] every day for decades.

There is also Pierpaoli work.

We discussed this in another thread a few months ago .

Review;

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I probably take more on average than RR and he is good on the research, but it is not a whole solution.

My understanding is smaller melatonin doses are more suitable for older adults.

Timing is critical as there are melatonin receptors on lots of things. Do you have a reference? I have taken doses Generally considered to be excessive for about 3 years.