Vascular risk factors, large-artery atheroma, and brain white matter hyperintensities

Abstract

Objective:To determine the magnitude of potentially causal relationships among vascular risk factors (VRFs), large-artery atheromatous disease (LAD), and cerebral white matter hyperintensities (WMH) in 2 prospective cohorts.Methods:We assessed VRFs (history and measured variables), LAD (in carotid, coronary, and leg arteries), and WMH (on structural MRI, visual scores and volume) in: (a) community-dwelling older subjects of the Lothian Birth Cohort 1936, and (b) patients with recent nondisabling stroke. We analyzed correlations, developed structural equation models, and performed mediation analysis to test interrelationships among VRFs, LAD, and WMH.Results:In subjects of the Lothian Birth Cohort 1936 (n = 881, mean age 72.5 years [SD ±0.7 years], 49% with hypertension, 33% with moderate/severe WMH), VRFs explained 70% of the LAD variance but only 1.4% to 2% of WMH variance, of which hypertension explained the most. In stroke patients (n = 257, mean age 74 years [SD ±11.6 years], 61% hypertensive, 43% moderate/severe WMH), VRFs explained only 0.1% of WMH variance. There was no direct association between LAD and WMH in either sample. The results were the same for all WMH measures used.Conclusions:The small effect of VRFs and LAD on WMH suggests that WMH have a large “nonvascular,” nonatheromatous etiology. VRF modification, although important, may be limited in preventing WMH and their stroke and dementia consequences. Investigation of, and interventions against, other suspected small-vessel disease mechanisms should be addressed.

Gliovascular Disruption and Cognitive Deficits in a Mouse Model with Features of Small Vessel Disease

“…However, it has since been shown that all vascular risk factors combined account for o2% of the variance in white matter hyperintensities. 2 Furthermore, despite major advances in blood pressure control, the incidence of SVD remains high, and this has failed to prevent the progression of white matter hyperintensities or lacunar stroke, 35 suggesting that other risk factors may be crucial to disease progression. Recent evidence from animal models also suggest that hypertension is not the key driver of white matter changes.…”

“…1 Hypertension is proposed to be a common risk factor (although it explains only a small proportion of imaging-determined SVD) and cerebral amyloid angiopathy is commonly present on pathologic examination. 2,3 Clinically, SVD is associated with early impairment of attention and executive function with slowing of information processing and motor deficits. 1 These clinical manifestations result primarily from the occurrence of lesions in the cerebral white matter, multiple lacunes within subcortical structures, atrophy, and, in some cases, microbleeds in deep gray matter, white matter, or at the corticosubcortical junction, identified by neuroimaging.…”

Gradual cerebral hypoperfusion in spontaneously hypertensive rats induces slowly evolving white matter abnormalities and impairs working memory

“…Alternatively, it might be plausible that hypertensioninduced vascular changes have a relatively minor contribution to development of human cerebral white matter hyperintensities as demonstrated in a recent cohort study of 881 community-dwelling old subjects and 257 patients with recent nondisabling stroke. 21 The current new model (SHR-2VGO) appears to include at least some important elements of the entire process of Binswanger disease, a pathological condition of SIVD, 22 leading from the initial process of hypertension to subsequent brain damage, whereas the existing models, such as WKY-2VO or WKY-2VGO, simulate only the downstream part of the pathophysiological cascade of small vessel disease.…”

Magnetic resonance imaging for assessment of cerebrovascular reactivity in cerebral small vessel disease: A systematic review

“…1 Clinically lacunar stroke and SVD are associated with some vascular risk factors such as hypertension, diabetes and smoking but have only weak associations with others such as large artery atheroma and atrial fibrillation. 5,6 While some SVD imaging features and large artery stroke can occur in the same individuals, in general, recurrent stroke tends to be of the same type as the initial stroke. 7 Additionally, SVD features associate more strongly with lacunar than cortical stroke.…”