Gray matter blood flow and volume are reduced in association with white matter hyperintensity lesion burden: a cross-sectional MRI study

Abstract

Cerebral White Matter Hyperintensities (WMH) are associated with vascular risk factors and age-related cognitive decline. WMH have primarily been associated with global white matter and gray matter (GM) changes and less is known about regional effects in GM. The purpose of this study was to test for an association between WMH and two GM imaging measures: cerebral blood flow (CBF) and voxel-based morphometry (VBM). Twenty-six elderly adults with mild to severe WMH participated in this cross-sectional 3 Tesla magnetic resonance imaging (MRI) study. MRI measures of GM CBF and VBM were derived from arterial spin labeling (ASL) and T1-weighted images, respectively. Fluid-attenuated inversion recovery (FLAIR) images were used to quantify the WMH lesion burden (mL). GM CBF and VBM data were used as dependent variables. WMH lesion burden, age and sex were used in a regression model. Visual rating of WMH with the Fazekas method was used to compare the WMH lesion volume regression approach. WMH volume was normally distributed for this group (mean volume of 22.7 mL, range: 2.2–70.6 mL). CBF analysis revealed negative associations between WMH volume and CBF in the left anterior putamen, subcallosal, accumbens, anterior caudate, orbital frontal, anterior insula, and frontal pole (corrected p < 0.05). VBM analysis revealed negative associations between WMH and GM volume in lingual gyrus, intracalcarine, and bilateral hippocampus (corrected p < 0.05). The visual rating scale corroborated the regression findings (corrected p < 0.05). WMH lesion volume was associated with intra-group GM CBF and structural differences in this cohort of WMH adults with mild to severe lesion burden.

A longitudinal characterization of perfusion in the aging brain and associations with cognition and neural structure

“…These results are support a previous cross-sectional study in older adults that found associations among ASL perfusion and GMV and cortical thickness (Alosco et al, 2013). Associations among perfusion, brain volume, WMHs, and cortical microbleeds have also been reported in cross-sectional studies of participants with a variety of vascular risk factors (Crane et al, 2015;Gregg et al, 2015;van Elderen et al, 2011).…”

Cerebral blood flow in small vessel disease: A systematic review and meta-analysis

“…Of these six studies, two included Alzheimer's disease (AD), 16,17 the other four focused on vascular dementia including subcortical vascular dementia, 18 multi-infarct dementia (MID), 19,20 and Binswanger's disease (BD). 5 AD diagnosis used the criteria of the National Institute of Neurological 10 Manifest arterial diseases a 57.0 AE 10.0 Phase-contrast MRI ml/100 ml/min Kraut et al 44 Progressive WMH 70.0 AE 6.9 PET Not shown Stable WMH 67.1 AE 7.0 ten Dam et al 12 History 45 Extensive WMH 71.0 ASL ml/100 g/min No or mild WMH 67.0 Fu et al 33 WMH 34 WMH Grade 3 b 77.7 AE 5.7 ASL ml/100 ml/min WMH Grade 2 74.4 AE 4.6 WMH Grade 1 74.0 AE 5.0 Zheng et al 22 Asymptomatic WMH 69.7 AE 8.9 SPECT ml/g/min No WMH 67.1 AE 6.9 Ramli et al 23 Leukoaraiosis 47 Mild to severe WMH 73.3 AE 8.8 ASL ml/100 g/min Alosco et al 40 Heart failure with WMH 68.55 AE 8.07 Ultrasound Doppler cm/s Heliopoulos et al 38 Hypertension with WMH 71.4 AE 4.5 Ultrasound Doppler cm/s van Es et al 13 Cerebrovascular risk factors without major neurological deficits 75.0 AE 3.0 Phase-contrast MRI ml/min, ml/100 ml/min Vernooij et al 14 Population-based 67.5 AE 5.5 Phase-contrast MRI ml/100 g/min Bisschops et al 42 Manifest arterial diseases a 59.0 Phase-contrast MRI ml/min Tzourio et al 37 Population-based 68.9 AE 2.9 Ultrasound Doppler m/s Ott et al 41 Mixed dementia 72.8 AE 8.7 SPECT %rCBF relative to cerebellum Claus et al 46 Non-demented WMH 65.0-85.0 d SPECT %rCBF relative to cerebellum Isaka et al 39 Cerebrovascular and Communicative Disorders and Stroke, and the Alzheimer's disease and Related Disorders Association (NINCDS/ADRDA) for probable AD. Vascular dementia diagnosis varied: CT/MRI evidence, DSM-III-R criteria, 5,19,20 Hachinski ischaemia scores 19 and the criteria of the State of California Alzheimer's Disease Diagnostic and Treatment Centres.…”

Invited Review: The spectrum of age‐related small vessel diseases: potential overlap and interactions of amyloid and nonamyloid vasculopathies

“…That vulnerability includes an associated increased risk of cerebral bleeding, which is not remarkable, as both CSVD variants show similar abnormal vessel wall weakness (tunica media degeneration, BBB damage, microaneurysm formation) prone to leakage and rupture. On the other hand, there are also DPA‐ and CAA‐related small vessel wall thickening, luminal narrowing and occlusions revealing the pathophysiological basis for additional autoregulatory disturbances, CBF reduction and hypoperfusion with the latter commonly associated with CMB and WMH burden . However, thus far it seems poorly understood whether there are disease specific CBF alteration patterns preferentially related to DPA or CAA .…”