Heterogeneity of White Matter Hyperintensities in Cognitively Impaired Patients With Cerebral Small Vessel Disease

Abstract

ObjectiveSimilar white matter hyperintensities (WMH) might have different impact on the cognitive outcomes in patients with cerebral small vessel disease (CSVD). This study is to assess the possible factors related to the heterogeneity of WMH in cognitively impaired patients with CVSD.MethodsWe analyzed data from a cohort of patients with CVSD who were recruited consecutively from the Beijing Tiantan Hospital from 2015 to 2020. WMH, lacunes, enlarged perivascular space (ePVS), microbleeds and lacunar infarcts were rated on brain MRI. A score of <26 on the Montreal Cognitive Assessment (MoCA) indicated cognitive impairment. A mismatch was defined as the severity of WMH not matching the severity of cognitive dysfunction. Type-1 mismatch was defined as a mild WMH (Fazekas score = 0-1) associated with cognitive impairment, and type-2 mismatch was defined as a severe WMH (Fazekas score = 5-6) associated with normal cognitive function. Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced SWI on 3-Tesla MRI was used to image the penetrating arteries in basal ganglia to explore the underlying mechanism of this mismatch. Multivariable logistic regression was used to analyze the association between the imaging features and cognitive impairment.ResultsIn 156 patients, 118 (75.6%) had cognitive impairment and 37 (23.7%) showed mismatch. Twenty five (16.0%) had type-1 mismatch and 12 (7.7%) had type-2 mismatch. Regression analysis found that WMH, lacunes, microbleeds and total CSVD scores were associated with cognitive impairment and were independent of vascular risk factors. However, lacunes, microbleeds and total CSVD scores were related to the mismatch between WMH and cognitive impairment (p=0.006, 0.005 and 0.0001, respectively). Specially, age and ePVS in basal ganglia were related to type-1 mismatch (p=0.04 and 0.02, respectively); microbleeds and total CSVD scores were related to type-2 mismatch (p=0.01 and 0.03, respectively). Although the severity of WMH was similar, the injury scores of penetrating arteries were significantly different between those with and without cognitive impairment (p=0.04).ConclusionsHeterogeneity of WMH was present in cognitively impaired patients with CSVD. Conventional imaging features and injury of penetrating arteries may account for such heterogeneity, which can be a hallmark for early identification and prevention of cognitive impairment.

Perfusion heterogeneity of cerebral small vessel disease revealed via arterial spin labeling MRI and machine learning

“…The heterogeneity of BBB permeability might account for the inconsistent perfusion patterns to some extent ( Rajani et al, 2019 ). Variances of MRI imaging features including WMH, lacune, CMBs, and EPVS among individuals may also account for the inconsistent perfusion patterns ( Wang et al, 2021 ). In addition, risk factors including hypertension, smoking and drinking may influence brain perfusion ( Yu et al, 2020 ).…”

New insights in addressing cerebral small vessel disease: Associated with extracellular fluid in white matter

“…CSVD is a clinical syndrome that affects small vessels. It has different clinical presentations and radiomic features ( Dey et al, 2019 ; Wang et al, 2021 ), which may be due to differences in its pathogenesis and severity. In patients with CSVD, cerebral blood flow is often low ( Zhang et al, 2022 ) and brain tissues are often ischemic, resulting in increased extracellular fluid volume.…”

Cerebral Small Vessel Disease: A Bibliometric Analysis

“…The main symptoms of CSVD patients include lower extremity motor dysfunction characterized by gait disturbance and cognitive dysfunction characterized by impaired executive function (Wang et al 2021 ; Biesbroek et al 2017 ). White matter lesions (WMLs) are more common in the elderly.…”

“…Ultimately, impaired autoregulation of the involved small vessels results in decreased cerebral blood flow and chronic cerebral hypoperfusion (Litak et al 2020), and occlusion of the arterial lumen leads to acute ischemia, leading to lacunar infarction (Tang and Liu 2021;Kim and Lee 2015). Severe stenosis and hypoperfusion involving multiple arterioles, mainly deep white matter, leading to incomplete ischemia, are seen on neuroimaging as "white matter hyperintensity" (WMH) (Wang et al 2021;Biesbroek et al 2017). The two pathophysiological pathways above may often overlap, so lacunar and white matter lesions often coexist.…”