Plasma Aβ, homocysteine, and cognition The Vitamin Intervention for Stroke Prevention (VISP) trial

Background: Amyloid-beta protein (A beta) plays a key role in Alzheimer disease (AD) and is also implicated in cerebral small vessel disease. Serum total homocysteine (tHcy) is a risk factor for small vessel disease and cognitive impairment and correlates with plasma A beta levels. To determine whether this association results from a common pathophysiologic mechanism, we investigated whether vitamin supplementation-induced reduction of tHcy influences plasma A beta levels in the Vitamin Intervention in Stroke Prevention (VISP) study. Methods: Two groups of 150 patients treated with either the high-dose or low-dose formulation of pyridoxine, cobalamin, and folic acid in a randomized, double-blind fashion were selected among the participants in the VISP study without recurrent stroke during follow-up and in the highest 10% of the distribution for baseline tHcy levels. Concentrations of plasma A beta with 40 (A beta 40) and 42 (A beta 42) amino acids were measured at baseline and at the 2-year visit. Results: tHcy levels significantly decreased with vitamin supplementation in both groups. tHcy were strongly correlated with A beta 40 but not A beta 42 concentrations. There was no difference in the change in A beta 40, A beta 42 (p = 0.40, p = 0.35), or the A beta 42/A beta 40 ratio over time (p = 0.86) between treatment groups. A beta measures were not associated with cognitive change. Conclusions: This double-blind randomized controlled trial of vitamin therapy demonstrates a strong correlation between serum tHcy and plasma A beta 40 concentrations in subjects with ischemic stroke. Treatment with high dose vitamins does not, however, influence plasma levels of A beta, despite their effect on lowering tHcy. Our results suggest that although tHcy is associated with plasma A beta 40, they may be regulated by independent mechanisms. Neurology (R) 2009;72:268-272