IIRC he said this has been progressing for years I.e. not delirium
Agmatine has nearly no bioavailability and an exceedingly transient half-life. It is actually labeled as “non-drug like” in most pharmacology sim databases.
Looking at anticholinergic drugs is a great idea as many elderly have extensive lists of medications which can impact cognitive reserve.
Short of cancer pain, there is no indication for chronic opioids.
This won’t be a popular opinion but there is literally nothing that can reverse dementia *once it is clinically apparent.* Monoclonal Ab’s Have been developed which can eradicate amyloid and tau in the brain and do not impact progression. This is because the organic mechanical damage to the neuron and neuronal circuits has already passed threshold for recovery. The trick is for earlier screening interventions.
As far as neuronal / symptomatic salvage, acetylcholine esterase inhibitors May prolong activity of daily living but again will not impact progression and most will have limited objective benefit.
*Early* cognitive impairment is best served by minimizing vascular risk factors (especially blood pressure and diabetes), low carbohydrate diets, and caloric restriction for those with metabolic syndrome. Supplement wise, Niagen, galantamine, DHA, possibly Ach sources (CDP choline, alpha GPC).
Source: I am a neurologist.
Great post - and yeah, the gradual decline does point to dementia. But gradual can be dependant on what exactly they are observing. Sometimes families see memory issues and slight confusion, that slowly turns into something more profound, like a sudden hallucination or loss of executive function, and they will describe it as gradual when really the newest item is more accute.
But yeah, I agree with being more gradual being more like the progression of dementia.
And I wholeheartedly agree that at some point it is like pissing in the wind trying to come up with natural substances to combat complex issues like this. People shouldn't get false hope or try to fully reverse damage that is already done.
As far as agmatine - not sure I agree on the bioavailability statement but you are correcy about the half life and elimination topic. Agmatine will not remain as agmatine in the system for very long. Its presense in plasma may only last minutes in a lot of cases, from what I have read, but it may remain in certain tissues longer.
Fortunately, IMO, agmatine does not need to stay agmatine to benefit dementia patients. Maybe I am wrong, but my reasoning is based on Dr. Carol Colton's work on Alzheimers and arginine deficiency.
She did show, albeit in mice, that DMFO reversed cognitive deficits on AD model mice. Now...IMO we lack a definitive pathology to alzheimers so two strikes - mice and the model itself.
But this research, to me, points toward a possoble pathology related to immune response and possible infection of some sort (I believe many diseases cause the over expression of arginase to cripple the immune response).
Arginine would be worthless in this scenario because it doesn't cross the BBB.
Agmatine, however. does cross the BBB, does inhibit arginase, retains much of the functionality if arginine and also increases arginine levels better than oral arginine.
Complete wild a$$ guess here, but norvaline may also have a benefit from this angle.
Additionally, the NO mediated effects of agm will improve cardiovascular health which should help delay the progression of dementia.
But to your point - not expecting much if any reversal and theory, not fact.
I still think it has health benefits regardless and is probably one of the best shots without creating a coctail of a handful of unknown drugs/ingredients that may just create more polypharmacy.
Would love to hear your thoughts on that mkre, given you actually know what you are talking about and I probably don't know what I don't know.