R544C Mutation을 가진 CADASIL 환자의 혈관성 위험인자
Vascular Risk Factors in CADASIL Patients with Notch3 R544C Mutation
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초록
Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited arteriopathy caused by mutation in the notch 3 gene. Characteristic features include recurrent ischemic stroke, migraine, and progressive cognitive decline. Despite the highly stereotyped nature of CADASIL, marked phenotypic variation has been reported, which suggest that other factors may modulate the disease process. Possible factors include both environmental and other genetic factor. In the present study we sought to determine whether conventional cardiovascular risk factors influence phenotype and MRI markers in CADASIL patients that carry an R544C mutation. Methods: Fifty three consecutive patients with R544C mutation were investigated. Then patients were divided into two groups depending on the presence (VR group) or absence (non-VR group) of conventional vascular risk factors. Vascular risk factors included hypertension, diabetes mellitus, hypercholesterolemia, ischemic heart disease, smoking, and heavy drinking. Thirty four patients belonged to VR group and the remaining 19 patients to the non-VR group. All patients underwent a detailed neuropsychological testing including Alzheimer’s disease assessment scale cognitive subscale (ADAS-cog) and MR imaging protocols. Results: VR group demonstrated an increase in lacunar infracts (p=0.038) and cerebral microbleeds (p=0.002). However, there was no significant difference in the ADAS-cog and MMSE scores between VR group and non-VR group. The memory scores of ADAS-cog (delayed recall test) were lower in VR group than non-VR group (p=0.049). However, digit span backward scores were lower in non-VR group than VR group (p=0.048). Conclusions: We observed increase in lacunar infarcts and cerebral microbleeds in VR group. These findings suggest that conventional vascular risk factor may predispose to cerebrovascular events in CADASIL patients with notch3 R544C mutation.
Abstract
Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited arteriopathy caused by mutation in the notch 3 gene. Characteristic features include recurrent ischemic stroke, migraine, and progressive cognitive decline. Despite the highly stereotyped nature of CADASIL, marked phenotypic variation has been reported, which suggest that other factors may modulate the disease process. Possible factors include both environmental and other genetic factor. In the present study we sought to determine whether conventional cardiovascular risk factors influence phenotype and MRI markers in CADASIL patients that carry an R544C mutation. Methods: Fifty three consecutive patients with R544C mutation were investigated. Then patients were divided into two groups depending on the presence (VR group) or absence (non-VR group) of conventional vascular risk factors. Vascular risk factors included hypertension, diabetes mellitus, hypercholesterolemia, ischemic heart disease, smoking, and heavy drinking. Thirty four patients belonged to VR group and the remaining 19 patients to the non-VR group. All patients underwent a detailed neuropsychological testing including Alzheimer’s disease assessment scale cognitive subscale (ADAS-cog) and MR imaging protocols. Results: VR group demonstrated an increase in lacunar infracts (p=0.038) and cerebral microbleeds (p=0.002). However, there was no significant difference in the ADAS-cog and MMSE scores between VR group and non-VR group. The memory scores of ADAS-cog (delayed recall test) were lower in VR group than non-VR group (p=0.049). However, digit span backward scores were lower in non-VR group than VR group (p=0.048). Conclusions: We observed increase in lacunar infarcts and cerebral microbleeds in VR group. These findings suggest that conventional vascular risk factor may predispose to cerebrovascular events in CADASIL patients with notch3 R544C mutation.
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