#61

This is a great thread. I enjoyed reading everyone’s contributions. I would like to add a different but I think complementary perspective. My step-son is a neuropsychologist affiliated with a major hospital where he does functional brain mapping daily as part of surgical procedures. He has seen both the functional and the physical condition of thousands of brains, most often related to concussions, strokes, AD, and seizures. His observations about the relationship between the extent of amyloid and tau deposits and the cognitive capabilities of AD patients was, for me, an eye opener. He says the correlation between deposits and tangles and cognitive capabilities is not high. He sees high performing individuals with severely damaged brains and vice versa. He says that some severely dysfunctional AD patients have no detectable amyloid or tau deposits or tangles. He does believe he sees a high correlation with what might be called diverse overeducation resultant from a lifetime of intense curiosity and experimentation in the world, and perhaps also lifelong physical fitness.

With all the dangers of introspection acknowledged, I believe I can at my advanced age identify life experiences that pushed my cognitive development in novel ways. I remember new windows opening when I learned how to play the drums (where it is necessary to separate and direct the actions of each hand and each foot). I recall several similar windows when I earned my pilot’s license, and before that when I learned how to sky dive. I sometimes sense being in a different mental world after a week or two working on statistical problems in research. The way my step-son and his surgical colleagues have come to think about the apparent contradictions is that cognitive reserve plays a big role in late life. My personal view is that novel events may contribute more to cognitive reserves than repetitive behavior with well learned events, even if those events are difficult. Having two left feet, as they say, I’m contemplating taking dancing lessons. Should be fun no matter what. This is speculation of course but a great deal remains speculative in the world of AD. May we all find novel engagements that interest us.

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#62

And because contrary evidence is always welcome, here’s Dr. Greger pouring cold water on exercise, mental stimulation, brain games, social interaction, cryotherapy, as interventions against dementia and AD, citing studies and highlighting reverse causality:

Improving cognitive function

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#63

ptau 217 is a little more accurate for diagnostic that 181 i think

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#64

Hello @DrFraser
Could you please go deeper into this topic?
Thanks

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#65

That’s a great list on thing to consider adding to it: Mexidol

150 mg 2x a day

#66

I’m unable to find any trial looking at this agent vs. dementia. It is an antioxidant, but I think Astathaxin is a potent option here that does have at least some evidence.

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#67

Interesting point, and yet the literature supports 181 ptau in mid age as being predictive of things to come, but with actual disease 217 ptau seems more specific. Also, just like B Amyloid ratio and 181 ptau, 217 ptau with Evexia/Lapcorp is $225. So all 3 $675.

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#68

I have that on the list, and there is a real question of long term valacyclovir for anyone with HSV-1 as it is likely a contributor to dementia.

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#69

Fascinating test, as with all of these, a wallet biopsy, and have to strategize what to pay for. I’ve added this to my list as it is interesting. I think the micronutrient panel with Vibrant is also of solid value as it looks at intracellular levels, as I find a lot of individuals have high serum levels of various nutrients, but low intracellular.

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#70

Neuroplasticity is important. I however think doing anything at a high level of mental effort, repetitively probably gets most of the benefit. It is depressing to me, to treat so many individuals in the ER who are in their 50’s, who are obese, smokers, insulin resistant, hypertensive, poorly educated and not mentally engaged who cannot answer a simple question. Their brains are already fried. Most will have a vascular event to kill or disable them before dementia sets in, but in my view, these folks already have Mild Cognitive Impairment (MCI), however, it may be life long.

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#71

I believe the Apoe-4 test costs $125 thru the Alzheimer’s organization.

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#72

I can order it from Boston Heart Labs, including a minimal admin fee $75 as a cheek swab. You can self order through EmpowerDx for $99.

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#73

As someone who first thought everyone here was speaking greek, this is the reason I practically live here now. I try to absorb everything said (unless it’s from you, @John_Hemming…maybe next year!!), and I even read some studies now. I haven’t found anything else online that makes my brain work as hard!

PS, I’m an advocate of being tested for APOE4. I went from being pretty sure I knew to being positive, and instead of being depressing, it was empowering because I’m now all in on prevention, instead of just being 80% there).

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#74

Note I heard about it on a podcast with Dr. Kaufmann. It seems interesting. Dosages and Links to Longevity Supplements — kaufmannprotocol.com | Kaufmann Protocol Longevity Program

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#75

The compound’s in vitro iron chelating property shows potential in the management of neurodegenerative conditions such as Alzheimer’s disease (AD), as well as hematologic disorders. Promising effects of emoxypine and its succinate derivative in the management of various diseases-with insights on recent patent applications - PMC

#76

Great list. Would add taurine and ubiquinol and acetyl l carnitine. Tadalifil/cialis 5mg daily improves blood flow and raises T cells. A peptide, thymosin alpha 1, increases NK cells and has antiviral efficacy. Vitamin K 2 as MK 4 and MK7 help with blood production and vessel stiffness.
You can get NT Factor from Researched Nutritionals without all the extra junk/vits.

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#77

APOE4 is very confusing and it certainly is not a death sentence, I think if you play cards right you could actually make it work for you. There are centerians with double APOE4.

https://www.nature.com/articles/s41598-023-41078-5

Abnormal cognitive ageing, including dementia, poses serious challenges to health and social systems in ageing populations. As such, characterizing factors associated with abnormal cognitive ageing and developing needed preventive measures are of great importance. The ε4 allele of the Apolipoprotein E gene (APOE4 ) is a well-known genetic risk factor for late-onset Alzheimer’s disease. APOE4 carriers are also at elevated risk of cardiovascular diseases which are associated with increased risk of cognitive impairment. On the other hand, APOE4 is known to be associated with reduced risk of multiple common types of cancer—a major age-related disease and leading cause of mortality. We conducted the first-ever study of APOE4’s opposing effects on cognitive decline and mortality using competing risk models considering two types of death—death with high-amounts versus low-amounts of autopsy-assessed Alzheimer’s neuropathology. We observed that APOE4 was associated with decreased mortality risk in people who died with low amounts of Alzheimer’s-type neuropathology, but APOE4 was associated with increased mortality risk in people who died with high amounts of Alzheimer’s-type neuropathology, a major risk factor of cognitive impairment. Possible preventive measures of abnormal cognitive ageing are also discussed.

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#78

Really nice set of suggestions. I’d put taurine/ubiquinol/acetyl l carnitine all the the group that demonstrate some evidence to help with cognition once you have MCI or Dementia.

Now with Ubiquinol or CoEnzymeQ10, I think I should add this as there is a strong association with deficiency and incident dementia.

The Tadalafil sadly looks to have fallen out to some degree in some recent articles talked about here on the board - but I’ll put that, along with the rest beyond it in the category of sensible supplements, especially to maintain vascular health.

I’ll need to come up with a much less impressive list of what to do for MCI, there are some things, such as these that have limited evidence.

My list, and it isn’t perfect by any means, more relates to items that I think, taken 20 years before onset of dementia, decrease the likelihood of you ever ending up with dementia.

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#79

To discover APOE4 status, may want to use a data collection service such as 23&me and run the genome raw data through Promethease. Then you can look up three other genes that are reputed to be potential risks (if mutated) for Alzheimers: APP, PSEN1 and PSEN2. I believe I first heard about these three from Peter Attia.

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#80

Choline acts as an antidote to some of the negative side-effects of anticholinergic medicines.

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