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

OBJECTIVE: Similar 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. METHODS: We 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. RESULTS: In 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). CONCLUSIONS: Heterogeneity 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.