In the past I’ve asserted that dementia conditions like AD were the product of advanced senescence, essentially the product of groups of cells “aging” faster than “average”, at least relative to the rest of the organism.
This assumption is almost certainly wrong, and long telomere (or whatever measure of senescence we apply) dementia is not only a thing, it’s not even uncommon.
IMO, ditching this assertion leaves us with a much more coherent metabolic model of nervous system function, most importantly better accommodating “early on-set” forms of defined conditions.
This leaves the majority of dementia effects as artifacts of mitochondrial function, with particulate etiologies resulting from protein production issues.
Should be noted that this understanding views mitochondria as primarily “translation” units in cells, and the “factory”/protein production conceit is an incomplete understanding of function. Mitos are responsible for storing external information and generating an output based on that stored information.
My current context for dementias are as either “translation” (cognitive issues) insults or “response” insults (over production/mis production of proteins which initiate protective responses).
Edit: Shower thought – Dementia plaques are evidence of memory leaking out of your brain.
Neurovascular coupling unit dysfunction and dementia: Retinal measurements as tools to move towards population-based evidence – This is such an obvious idea I’m angry I didn’t think of it. I think we could probably diagnose nearly all “neuro” prefix conditions with better sensitivity and accuracy with some type of retinal observation scheme.
Because of the sensitivity of retinal astrocytes, they kind of work like a canary in the coal mine for many types of dementia. Due to the circuits recruited by the optical path, including the low level brainstem/salience portion, I’d imagine we might be able to suss out symptoms of future physiological issues that clinical observation/interoception may miss. I think there’s a good chance a retinal based dementia prediction scale will have far higher sensitivity and accuracy than even the gold standard genetic etiologies like trisomy or double APOE4.