Evaluation of Cerebral Blood Flow Measured by 3D PCASL as Biomarker of Vascular Cognitive Impairment and Dementia (VCID) in a Cohort of Elderly Latinx Subjects at Risk of Small Vessel Disease.

Kay Jann,Steven Y Cen,Lina D’Orazio,John M Ringman,Lirong Yan,Adam M Staffaroni,Xingfeng Shao,Marlena Casey,Samantha J Ma,Giuseppe Barisano,Jesse Lamas,Danny J J Wang,Joel H Kramer

doi:10.3389/fnins.2021.627627

Abstract

Cerebral small vessel disease (cSVD) affects arterioles, capillaries, and venules and can lead to cognitive impairments and clinical symptomatology of vascular cognitive impairment and dementia (VCID). VCID symptoms are similar to Alzheimer’s disease (AD) but the neurophysiologic alterations are less well studied, resulting in no established biomarkers. The purpose of this study was to evaluate cerebral blood flow (CBF) measured by 3D pseudo-continuous arterial spin labeling (pCASL) as a potential biomarker of VCID in a cohort of elderly Latinx subjects at risk of cSVD. Forty-five elderly Latinx subjects (12 males, 69 ± 7 years) underwent repeated MRI scans ∼6 weeks apart. CBF was measured using 3D pCASL in the whole brain, white matter and 4 main vascular territories (leptomeningeal anterior, middle, and posterior cerebral artery (leptoACA, leptoMCA, leptoPCA), as well as MCA perforator). The test-retest repeatability of CBF was assessed by intra-class correlation coefficient (ICC) and within-subject coefficient of variation (wsCV). Absolute and relative CBF was correlated with gross cognitive measures and domain specific assessment of executive and memory function, vascular risks, and Fazekas scores and volumes of white matter hyperintensity (WMH). Neurocognitive evaluations were performed using Montreal Cognitive Assessment (MoCA) and neuropsychological test battery in the Uniform Data Set v3 (UDS3). Good to excellent test-retest repeatability was achieved (ICC = 0.77–0.85, wsCV 3–9%) for CBF measurements in the whole brain, white matter, and 4 vascular territories. Relative CBF normalized by global mean CBF in the leptoMCA territory was positively correlated with the executive function composite score, while relative CBF in the leptoMCA and MCA perforator territory was positively correlated with MoCA scores, controlling for age, gender, years of education, and testing language. Relative CBF in WM was negatively correlated with WMH volume and MoCA scores, while relative leptoMCA CBF was positively correlated with WMH volume. Reliable 3D pCASL CBF measurements were achieved in the cohort of elderly Latinx subjects. Relative CBF in the leptomeningeal and perforator MCA territories were the most likely candidate biomarker of VCID. These findings need to be replicated in larger cohorts with greater variability of stages of cSVD.

Highlights

While Alzheimer’s disease (AD) is the most common cause of dementia, the contribution of vascular factors to cognitive impairment and dementia is becoming increasingly recognized (Gorelick et al, 2011)
Based on our hypothesis and literature evidence, we focused on CBF measurements in 3 regions for correlation with behavioral and imaging biomarkers of Cerebral small vessel disease (cSVD): leptomeningeal middle cerebral artery (MCA) and MCA perforator (MCAperf) territories, and white matter (WM)
Relative CBF normalized by global mean CBF in the leptoMCA territory was positively correlated with an IRT-derived composite score of executive function, while relative CBF in the MCA perforator and leptoMCA territory was positively correlated with Montreal Cognitive Assessment (MoCA) scores of global cognitive function

Summary

Introduction

While Alzheimer’s disease (AD) is the most common cause of dementia, the contribution of vascular factors to cognitive impairment and dementia is becoming increasingly recognized (Gorelick et al, 2011). AD and cerebrovascular diseases share common risk factors such as hypertension, obesity, diabetes, and these conditions coexist in 40–50% of clinically diagnosed AD, making mixed AD-vascular dementia the most common cause of cognitive impairment in the aged (Iadecola, 2016). Cerebral small vessel disease (cSVD) is the most common vascular cause of dementia, a major contributor to mixed dementia, and the cause of about one fifth of all strokes worldwide (Norrving, 2008; Pantoni, 2010). The underlying mechanisms of cSVD remain poorly understood, resulting in no specific guidelines for its prevention and treatment

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