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). A unique 4D-Flow magnetic 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. A subset 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 (ROC) 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-β (Aβ42), total-tau and total-tau/Aβ42 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 Aβ42 had lower ICA mean flow than did those who were Aβ42 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.

Assessment of vascular stiffness in the internal carotid artery proximal to the carotid canal in Alzheimer’s disease using pulse wave velocity from low rank reconstructed 4D flow MRI

“…51 While 4D flow MRI studies have correlated higher pulsatility of intracranial arteries and veins with AD pathology. 11–13,52 Furthermore, vessel pulsatility has been speculated as a driver of glymphatic flow, as the motive force for perivascular drainage of interstitial fluid, Aβ, and other soluble metabolites. 53,54 Cardiac pulsations may also contribute to clearance of soluble metabolites from the brain by mixing and dispersion effects.…”

4D flow MRI for non-invasive measurement of blood flow in the brain: A systematic review

“…They found that lower mean flow of the middle cerebral arteries (MCAs) and internal carotid arteries (ICAs) was associated with greater brain atrophy, as was increased MCA stiffness (represented as Gosling’s Pulsatility Index equation, PI = (flow max – flow min )/flow mean ); they also found decreased mean flow in the ICAs was associated with lower amyloid beta in the CSF. The same group carried out a similar study two years later, 12 with subjects undergoing a neuropsychiatric battery and lumbar puncture (for CSF assay). They found an association between ICA and MCA mean flow and executive functioning performance, as well as evidence of an association between decreased blood flow and amyloid beta deposition across 38 MCI subjects, correcting for age and sex.…”

Role of Body-Fluid Biomarkers in Alzheimer’s Disease Diagnosis

“…In addition, blood samples can be very easily collected from the patients, while the collection of the CSF samples needs procedures that require lumber punctures. Therefore, it becomes a great drawback of the CSF biomarkers in comparison to the blood biomarkers [75,76] due to its stability. However, assaying Aβ proteins in the blood becomes difficult when other proteins present in the blood interfere with the procedure, or the sample can even undergo photolytic reactions [18].…”