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.
Highlights
Cerebral small vessel disease (CSVD) is generally caused by disorders of the intrinsic cerebral arteriolar system [1]
The results suggested that the injury degree of penetrating arteries in the basal ganglia might be responsible for the cognitive impairment in patients with similar severity of White matter hyperintensities (WMH), causing WMH heterogeneity in CSVD patients with cognitive impairment
2) We found that in addition to conventional factors, e.g. age, BG-enlarged perivascular space (ePVS), microbleeds and total CSVD score, the injury to penetrating arteries might be the important contributor to this mismatch, which might increase the risk of cognitive impairment when under similar WMH
Summary
Cerebral small vessel disease (CSVD) is generally caused by disorders of the intrinsic cerebral arteriolar system [1]. White matter hyperintensities (WMH) are the most common feature of CSVD on brain magnetic resonance imaging (MRI) [3] with a prevalence up to 94% in the general population aged around 80 [4]. It is associated with cognitive decline, a 90% increased risk of dementia and a 200% increased risk of stroke [5]. Several studies have focused on the association between WMH and clinical outcomes Most of these studies found that extensive WMH burden was usually associated with increased risk of incident stroke, dementia and mortality in general population or in populations at high risk for vascular disease or dementia [6]. The effect of such heterogeneity of WMH on clinical symptoms remains uncertain
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