Plasma Abeta, homocysteine, and cognition: the Vitamin Intervention for Stroke Prevention (VISP) trial
Viswanathan A, Raj S, Greenberg SM, Stampfer M, Campbell S, Hyman BT, et al.;
Commented by , 17 Feb 2009
Aim of the study
To determine if vitamin supplementation-induced reduction in total homocysteine (tHcy) blood level influences plasma Aß levels.
Method
The Vitamin Intervention in Stroke Prevention (VISP) study aimed at reducing over two years in patients with an ischemic stroke the incidence of recurrent stroke or myocardial infarct by lowering tHcy levels with large versus low doses of folic acid, pyridoxine and vitamin B12 (ref. 1).
The VISP study was negative but allowed for an add-on component using a random sample of two groups of 150 patients among the highest 10% of the distribution for baseline tHcy levels, who did not have a recurrent stroke during the 2-year study. Concentrations of plasma Aß with 40 (Aß40) and 42 (Aß42) amino acids were measured at baseline and at the 2-year visit, using an ELISA technique.
Results
tHcy blood levels were lowered by vitamin supplementation in both low and high doses groups (significantly more in the high dose group; p < 0.0001). tHcy levels were strongly correlated with Aß40 at baseline and after 2 years (r = 0.25 and 0.29,
p < 0.0001), but not the Aß42 concentrations. There was no difference in Aß40, Aß42 or the Aß40/ Aß42 ratio over time between treatment groups. Aß levels did not influence changes in the Mini Mental State Examination scores over the treatment period.
Professor Gauthier's comments
The authors conclude that vitamin supplementation does reduce tHcy levels, which are strongly correlated to plasma Aß40 concentrations in patients with ischemic stroke. Treatment with high dose of vitamins does not influence plasma levels of Aß, despite their effect on lowering tHcy, suggesting independent regulatory mechanisms.
Although these results are overall negative for stroke prevention over 2 years, this study is important for the following reasons:
- Add-on components looking at cognitive changes and biological parameters relevant to dementia can be built into large scale stroke studies.
- The methodology to measure Aß in plasma is constantly evolving, and allows for a less invasive than lumbar puncture assessment of a key biological marker of Alzheimer’s disease. Even ß-amylod oligomers are now measurable in human plasma using ELISA (ref. 2).
- Vitamin supplements, especially in high doses, require prospective randomized clinical trials to assess their safely and efficacy.
References
1. Toole JF, Malinow MR, Chambless LE, Spence JD, Pettigrew LC, Howard VJ, et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 2004; 291(5); 565-575
2. Xia W, Yang T, Shankar G, Smith IM, Shen Y, Walsh DM, et al. A specific enzyme-linked immunosorbent assay for measuring beta-amyloid protein oligomers in human plasma and brain tissue of patients with Alzheimer disease. Archives of Neurology 2009; 66 (2); 190-199