Isn't it possible the the folate/Vitamin B regiment, besides lowering tHcy, manifested an improvement in dementia by some other completely unrelated (i.e. not measured) effect? Why must it be that the folate/Vitamin B regiment is unequivocally connected to dementia reduction via only tHcy reduction (but only for high tHcy participants)?
From what I have read about tHcy and direct AD cause/effect, it still a theory?
Smith and Refsum are certainly moving things from correlation towards causation in very well-controlled studies when age appropriate participants are used, and homocysteine is checked pre and post treatment. And you're correct, only in those with high homocysteine is a positive effect noted. Re. MOA, homocysteine tracks very nicely with multiple markers: cognition, white matter hyperintensities, hippocampal volume, etc. and
the trifecta of B's lower homocysteine... but I suppose it could be a red herring. That being said, as someone at very high risk for AD, I'd be hard pressed to NOT maintain low Hcy, but you're welcome to wait until it is proven to your satisfaction.