Brain damage caused by small vessel disease (SVD) differs between males and females. We aimed to examine the pure sex-specific neuroanatomical mechanisms of SVD adjusted for voxel-based expected effects of age and sex on healthy brain volume. Thirty-one female and 32 male genetic SVD (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, CADASIL) patients and 55 sex- and age-matched healthy controls (HCs) underwent 7-Tesla MRI examinations. Voxel-based W-score maps were calculated from volumes and deformations of brain tissues, controlling for the expected effects of age and sex in HCs. Significant cognitive declines in working memory and executive function were identified in male CADASIL patients compared to female patients. Greater gray matter (GM) atrophy was found in the bilateral orbitofrontal cortex (OFC), left anterior cingulate cortex (ACC), left entorhinal cortex (EC), and right temporooccipital cortex in male CADASIL patients than in females. Working memory was associated with volumes in the right OFC specific to female CADASIL patients, whereas visuospatial ability was associated with the right hOcl (primary visual area, BA 17) volume specific to males. The current findings indicate that sex affects the pathogenesis of CADASIL, ranging from differences in neuroanatomy to those in behavioral performance, which may facilitate the development of more effective sex-specific therapeutic strategies for CADASIL and SVD.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9813786 | PMC |
Neurology
January 2025
From the ARAMIS (S.K., S.T.D.M.), Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, CNRS, Inria, Inserm, AP-HP, Groupe Hospitalier Sorbonne Université; Centre de référence pour les maladies vasculaires rares du cerveau et de l'œil (CERVCO) and Centre Neurovascular Translationnel (CNVT) (D.H., A.J., S.R., C.M., S.G., A.T., F.F., H.C.), AP-HP, Paris; and INSERM U1141 - FHU NeuroVasc (D.H., S.G., H.C.), Université Paris Cité, France.
Background And Objectives: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent small artery brain disease caused by pathogenic variants of the NOTCH3 gene. During the disease, we still do not know how the various deficits progress and develop with each other at different stages of the disease. We aim to model disease progression and identify possible progressive subgroups and the effects of different covariates on clinical worsening.
View Article and Find Full Text PDFNeurol Sci
December 2024
UOSD Centro Demenze, University of Rome Tor Vergata, Viale Oxford 81, 00133, Rome, Italy.
Introduction: The NOTCH3 gene encodes for an evolutionarily conserved protein, whose functions encompass both embryonic cell proliferation and adult tissue-specific differentiation. Among others, a pivotal role in maintaining functional integrity of neurovascular unit (NVU) is supported by the association of several NOTCH3 gene mutations with neuroimaging markers of cerebral small vessel disease (SVD). Indeed, a pathogenic role of NOTCH3 is recognised in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
View Article and Find Full Text PDFCureus
November 2024
Health Science, Fukui Health Science University, Fukui, JPN.
This report describes the case of a 48-year-old Japanese man with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) who also presented with aortic dissection. The patient had a history of hypertension, diabetes mellitus, dyslipidemia, and mild renal failure but had not received any treatment. He developed back pain and was diagnosed with type A aortic dissection via contrast-enhanced chest computed tomography (CT).
View Article and Find Full Text PDFJAMA Neurol
November 2024
Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Neurologist
November 2024
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
Introduction: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease with slow natural progression. Ischemic stroke and cognitive impairment are its most common clinical symptoms. Here, we report a rare 50-year-old woman who had rapid disease progression with c.
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