By the time the first symptoms of Alzheimer's disease show up, how much damage has the brain susta… by Steven Fowkes
Answer by Steven Fowkes:
I’m going to disagree with most of the experts so far. I think the answer is “minimal.”
Let me begin to qualify that by stating that there is much accumulated metabolic damage before onset of symptoms. The brain’s energy systems have been seriously down-regulated over years if not decades. Redox-control systems (NADH>>NADPH>>GSH>>ascorbate) have gotten weaker. There may be vascular changes. There are likely cell-population changes. And certainly there is a deepening and widespread edema of the brain. But I do not consider these “damage” in the sense of irreversibility. I think the connotation of damage is loss of brain cells.
I consider the “onset” of Alzheimer’s disease to be the specific metabolic changes of the Alzheimer’s “cascade failure” and NOT the predisposing factors that led up to the cascade. In other words, insulin resistance is a causal mechanism for Alzheimer’s disease, but it is not an essential mechanism; you can have Alzheimer’s disease without having high insulin resistance. Dale Bredesen now recognizes five types of Alzheimer’s disease, each of which has a different contribution from the many predisposing factors. But the onset of Alzheimer’s disease DOES have a metabolic signature that is essential (i.e., common to ALL Alzheimer’s diseases).
So I consider that essential metabolic cascade to be the actual onset of to Alzheimer’s disease. I doubt that this is the case for other answers.
Let me point out one aspect of Alzheimer’s disease that is frequently misinterpreted as “brain damage” and “loss of neurons” that is really just edema. Brain images of people with Alzheimer’s disease and other dementias (and neither) can show shrinkage of the brain and fluid accumulation around the brain. This can be interpreted as brain shrinkage from loss of neurons. I have had several clients who were told this. Literally. Even though it COULD be from loss of neurons, it is far more likely not. When metabolic rate is raised, the brain absorbs the fluid and expands to fill the skull again. If the shrinkage of the brain can be reversed in days, it is NOT a sign of cumulative neuronal death.
In other words, I do not consider brain edema to be damage. It is temporary. It is easily reversible. It is non-essential.
There are other answers on Quora (and a video series on YouTube) where I have gone into more depth on the essential metabolic disturbance of Alzheimer’s disease, so I’ll only summarize it here: it is the systematic loss of sulfhydryl-containing enzyme activity in the brain. In Alzheimer’s disease, the sulfhydryl-containing enzymes are decimated, and non-sulfhydryl enzymes are minimally affected or collaterally affected.
So, in answer to your question, the amount of neuronal death prior to (1) the loss of sulfhydryl enzyme activity, (2) the loss of microtubule-based axonal and dendritic transport, (3) the loss of creatine phosphate back-up energy reserves, and (4) the loss of the 90-second phosphorylation rhythm (phosphorylase-phosphatase cycling) is minimally different from any other normative disease of aging. In other words, if Alzheimer’s disease is rapidly reversed within weeks of onset, the loss of cognitive capabilities will be trivial.
Now that Alzheimer’s disease reversal is becoming mainstream at a research level, we will have the opportunity to test this hypothesis.
I hope this provides a different perspective than other answers.