Intracranial Arterial 4D Flow in Individuals with Mild Cognitive Impairment is Associated with Cognitive Performance and Amyloid Positivity

Abstract

It is becoming increasingly recognized that cerebrovascular disease is a contributing factor in the pathogenesis of Alzheimer's disease (AD). Aunique 4D-Flowmagnetic resonance imaging (MRI) technique, phase contrast vastly undersampled isotropic projection imaging (PC VIPR), enables examination of angiographic and quantitative metrics of blood flow in the arteries of the Circle of Willis within a single MRI acquisition. Thirty-eight participants with mild cognitive impairment (MCI) underwent a comprehensive neuroimaging protocol (including 4D-Flow imaging) and a standard neuropsychological battery. Asubset of participants (n = 22) also underwent lumbar puncture and had cerebrospinal fluid (CSF) assayed for AD biomarkers. Cut-offs for biomarker positivity in CSF resulting from a receiver operating characteristic curve analysis of AD cases and controls from the larger Wisconsin Alzheimer's Disease Research Center cohort were used to classify MCI participants as biomarker positive or negative on amyloid-beta (A beta(42)), total-tau and total-tau/A beta(42) ratio. Internal carotid artery (ICA) and middle cerebral artery (MCA) mean flow were associated with executive functioning performance, with lower mean flow corresponding to worse performance. MCI participants who were biomarker positive for A beta(42) had lower ICA mean flow than did those who were A beta(42) negative. In sum, mean ICA and MCA arterial flow was associated with cognitive performance in participants with MCI and lower flow in the ICA was associated with amyloid positivity. This provides further evidence for vascular health as a contributing factor in the etiopathogenesis of AD, and could represent a point to intervene in the disease process.