Abstract
Background: It remains unclear whether the degree of white matter tract damage or cerebral hypoperfusion can better predict global cognitive impairment in CADASIL. We sought to determine the independent effects of cerebral perfusion status and white matter integrity on the cognition.Methods: We reviewed prospectively collected clinical and imaging data from genetically-confirmed CADASIL patients who underwent both arterial spin labeling (ASL) perfusion MRI and diffusion tensor imaging (DTI). We analyzed the cerebral blood flow (CBF), mean diffusion (MD), and fractional anisotropy (FA) by dividing the brain tissue into white matter hyperintensity (WMH) and normal-appearing white matter (NAWM). Global cognitive function was evaluated by using Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA).Results: Of the included 29 CADASIL patients, the mean age was 48.4 ± 7.9 years, and 17 (58.6%) were women. MD was significantly correlated with CBF in both WMH (r = −0.407, P = 0.035) and NAWM (r = −0.437, P = 0.023) after adjusting for age and WMH volume. A MoCA score was obtained in 13 patients and was significantly correlated with CBF in both WMH (r = 0.742, P = 0.004) and NAWM (r = 0.659, P = 0.014). Both CBF in WMH (area under the curve, 0.767; 95% CI, 0.586-0.947, P = 0.015) and MD in WMH (area under the curve, 0.740; 95% CI, 0.557–0.924, P = 0.028) were good predictors for cognitive impairment (MMSE score < 27). However, multiple linear regression analysis revealed that global cognitive function was independently associated with CBF in WMH only (standardized β = 0.485, P = 0.015), after adjusting for age, gender, WMH volume, the presence of subcortical infarcts and DTI metrics.Conclusions: Our findings suggested that cerebral hypoperfusion was more strongly associated with global cognitive dysfunction than the severity of brain microstructural damage, supporting that CBF assessed by ASL could serve as a candidate imaging indicator for monitoring alterations of global cognitive function in CADASIL.
Highlights
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an early-onset monogenic variant of cerebral small vessel disease (CSVD) caused by mutations in the NOTCH3 gene [1], whose prevalence is at least 4.6 per 100,000 adults [2]
We enrolled patients who (i) had a deleterious mutation of NOTCH3; (ii) underwent both arterial spin labeling (ASL) and diffusion tensor imaging (DTI) at the same time; and (iii) received a cognitive function assessment based on the Mini-Mental State Examination (MMSE) and/or the Montreal Cognitive Assessment (MoCA)
After adjusting for age and white matter hyperintensities (WMHs) volume, mean diffusivity (MD) was significantly correlated with cerebral blood flow (CBF) in both WMH (r = −0.407, P = 0.035) and normal-appearing white matter (NAWM) (r = −0.437, P = 0.023), while there lacked of an association between fractional anisotropy (FA) and CBF in both WMH (r = 0.196, P = 0.328) and NAWM (r = 0.159, P = 0.427) (Table 2)
Summary
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an early-onset monogenic variant of cerebral small vessel disease (CSVD) caused by mutations in the NOTCH3 gene [1], whose prevalence is at least 4.6 per 100,000 adults [2]. Previous studies have shown that the degree of white matter tract damage may relate to global cognitive function [9, 10]. Cerebral hypoperfusion was found to be correlated with cognitive impairment or dementia in CADASIL [11, 12]. It’s unclear whether white matter integrity or cerebral perfusion condition could better predict the global cognitive outcome. It remains unclear whether the degree of white matter tract damage or cerebral hypoperfusion can better predict global cognitive impairment in CADASIL. We sought to determine the independent effects of cerebral perfusion status and white matter integrity on the cognition
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