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No study yet has compared the longitudinal course and prognosis between subcortical vascular cognitive impairment patients with and without genetic component. In this study, we compared the longitudinal changes in cerebral small vessel disease markers and cognitive function between subcortical vascular mild cognitive impairment (svMCI) patients with and without variant [(+) svMCI vs. (-) svMCI]. We prospectively recruited patients with svMCI and screened for variants by sequence analysis for mutational hotspots in the gene. Patients were annually followed-up for 5 years through clinical interviews, neuropsychological tests, and brain magnetic resonance imaging. Among 63 svMCI patients, 9 (14.3%) had either known mutations or possible pathogenic variants. The linear mixed effect models showed that the (+) svMCI group had much greater increases in the lacune and cerebral microbleed counts than the (-) svMCI group. However, there were no significant differences between the two groups regarding dementia conversion rate and neuropsychological score changes over 5 years.
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http://dx.doi.org/10.3389/fneur.2021.586366 | DOI Listing |
J Integr Neurosci
August 2025
Key Laboratory of Modern Toxicology of Ministry of Education; School of Basic Medical Sciences, Nanjing Medical University, 211166 Nanjing, Jiangsu, China.
Cognitive impairment represents a progressive neurodegenerative condition with severity ranging from mild cognitive impairment (MCI) to dementia and exerts significant burdens on both individuals and healthcare systems. Vascular cognitive impairment (VCI) represents a heterogeneous clinical continuum, spanning a spectrum from subcortical ischemic VCI (featuring small vessel disease, white matter lesions, and lacunar infarcts) to mixed dementia, where vascular and Alzheimer's-type pathologies coexist. While traditionally linked to macro- and microvascular dysfunction, the mechanisms underlying VCI remain complex.
View Article and Find Full Text PDFNeurol Genet
October 2025
Department of Neurology, National Taiwan University Hospital, Taipei.
Background And Objectives: Vascular NOTCH3 extracellular domain (NOTCH3ECD) deposition is the pathologic hallmark of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We aimed to explore the relationships among the NOTCH3ECD deposition load, the variant genotype, and cerebral small vessel disease (SVD) severity.
Methods: Fifty-four individuals carrying pathogenic variants were enrolled and underwent skin biopsy for the quantification of dermal vascular NOTCH3ECD deposition load using immunohistochemical staining.
J Alzheimers Dis
September 2025
Department of Rehabilitation Medicine, The Second Affiliated Hospital of Shenzhen University, Shenzhen, China.
BackgroundThe progression of cerebral small vessel disease (CSVD) leads to cognitive decline, which can be categorized into subcortical vascular mild cognitive impairment (svMCI) and vascular dementia (VaD).ObjectiveThis research aimed to examine the structural changes in gray (GM) and white matter (WM) in the brain across the disease spectrum.MethodsA total of 30 healthy controls (HC), 26 individuals with svMCI, and 29 individuals with VaD were included in study.
View Article and Find Full Text PDFGene
August 2025
Neurology Department of Chongqing Wulong People's Hospital, Chongqing, Wulong 408599, China; Department of Neurology, Third Affiliated Hospital of Guizhou Medical University, Guizhou, Duyun 558099, China; Department of Neurology, Wulong Branch, Affiliated People's Hospital of Chongqing University, C
Vascular dementia (VaD) is the second largest type of dementia in the world after Alzheimer's disease, characterized by selective loss of neurons caused by cerebrovascular disease, dysfunction of cortical subcortical circuits, and cognitive domain specific damage. This article systematically analyzes some gene expression regulation issues in VaD pathogenesis from five dimensions: abnormal gene expression profile, epigenetic modification abnormality, transcription factor (TF) cascade regulation, non coding RNA (ncRNA) regulatory axis disorder, and gene environment interaction. For the first time, the "Dynamic Imbalance Theory of Gene Regulation Network" (DIGRN) is proposed.
View Article and Find Full Text PDFGenes (Basel)
July 2025
Neuroradiology Unit, Ospedale Santa Maria della Misericordia, AULSS 5 Polesana, 45100 Rovigo, Italy.
: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a prevalent Mendelian disorder caused by mutations in the gene, primarily impacting cerebral small blood vessels. This review aims to explore the involvement of large intracranial arteries in CADASIL, particularly focusing on the association with polymorphisms, especially in Asian populations. : A comprehensive literature review was conducted to gather data on the morphological features of both small and large intracranial arteries in CADASIL, examining clinical manifestations, imaging findings, and genetic associations.
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