Cognitive impairment occurs in ~70% of multiple sclerosis patients (MSP). The neural mechanism of this slowing is unknown. Vascular compliance reductions along the cerebrovascular tree would result in suboptimal vasodilation upon neural stimulation (i.e., neural-vascular uncoupling) and thus cognitive slowing. We tested arterial and venous cerebrovascular reactivity (CVR) along the cerebrovascular tree in nested cerebral cortical layers. Arterial CVR reduced exponentially along the cortical layers in controls and cognitively-normal MSP, but not in slower MSP. The exponential decay-constant was associated with individual subjects’ reaction-time. Such associations implicate neural-vascular uncoupling as a mechanism of cognitive slowing in MS.