Arginine impairs endothelial and executive function in older subjects with cardiovascular risk

Neurovascular coupling, the relationship between cerebral blood flow and neuronal activity, is attenuated in patients with impaired executive function. We tested the hypothesis that peripheral vascular function may associate with executive function in older subjects with cardiovascular risk factors and that treatment with the antioxidant L-arginine would improve both vascular and executive function. Nineteen subjects with type 2 diabetes mellitus and/or controlled hypertension were enrolled. Subjects were treated with L-arginine or placebo for 4 days in a randomized, double-blinded, cross-over study. Brachial artery vascular function, peripheral artery tonometry, and Trail Making Test Part B testing were performed on day 1 and day 4 during each condition. L-arginine significantly reduced the digital reactive hyperemia index, and the comparison of changes against placebo was significant (P = .01). With executive function testing, we observed a significant interaction between treatment and order. Restricting the analysis to the first treatment period, subjects treated with placebo decreased their Trail Making Test Part B times by 57.3 ± 52.5 seconds from day 1 to day 4 (P = .01) while those treated with arginine had no significant change (6.4 ± 18.4 seconds worse, P = .37). In addition, L-arginine was associated with increased mean arterial pressure from 88 ± 9 mm Hg to 92 ± 11 mm Hg, which trended toward significance. L-arginine treatment worsened digital microvascular and executive function in older subjects with cardiovascular risk factors. These data further support a link between vascular and executive function.