Related Experiment Video
Updated: Jun 11, 2025
Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions
Published on: April 23, 2021
White Matter Hyperintensities and Cognitive Functions in People With the R544C Variant of the NOTCH3 Gene Without
Hsin Tung1, Chien-Chih Chou1, Hsian-Min Chen1
1From the Department of Post-Baccalaureate Medicine (H.T., C.-C.C., Y.-M.C., W.-J.L.), College of Medicine, National Chung Hsing University; Center of Faculty Development (H.T.), Department of Medical Education, and Department of Neurology (H.T., W.-J.L.), Neurological Institute, Taichung Veterans General Hospital; Graduate Institute of Clinical Medicine (C.-C.C.), College of Medicine, National Taiwan University, Taipei; Department of Ophthalmology (C.-C.C.), Taichung Veterans General Hospital; School of Medicine (C.-C.C., Y.-M.C., H.-C.C.), National Yang Ming Chiao Tung University, Taipei; Center for Quantitative Imaging in Medicine (H.-M.C.), Department of Medical Research, Division of Allergy, Immunology and Rheumatology (Y.-M.C.), Department of Internal Medicine, and Department of Medical Research (Y.-M.C.), Taichung Veterans General Hospital; Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine & Program in Translational Medicine (Y.-M.C.), and Precision Medicine Research Center (Y.-M.C.), College of Medicine, National Chung Hsing University, Taichung; Department of Radiology (Y.-Y.W., J.-W.C., H.-C.C.), Taichung Veterans General Hospital; Department of Electrical Engineering (Y.-Y.W.), National Chung Hsing University, Taichung; Biostatistics Task Force of Taichung Veterans General Hospital (J.-P.C.), Taichung; Institute of Statistical Science (S.-C.C.), Academia Sinica, Taipei; Dementia Center (W.-J.L.), Taichung Veterans General Hospital; and Brain Research Center (W.-J.L.), National Yang Ming Chiao Tung University, Taipei, Taiwan.
Background And Objectives:
NOTCH3 pathologic variants cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which presents with stroke and dementia and is characterized by white matter hyperintensities (WMHs) on brain MRI. The R544C variant is a common pathologic variant in Taiwan, but not all carriers exhibit significant symptoms. We investigated whether WMHs occur before clinical symptoms in carriers with pathogenic variants, examined factors associated with WMHs, and explored their relationship with cognitive functions.
Methods:
We enrolled 63 R544C carriers without overt clinical disease (WOCD) and 37 age-matched and sex-matched noncarriers as controls from the Taiwan Precision Medicine Initiative data set. All participants underwent clinical interviews, comprehensive neuropsychological assessments, and brain MRI. We calculated total and regional WMH volumes, determined the age at which WMHs began increasing in carriers, and examined the relationship between WMHs and neuropsychological performance. Factors associated with WMH volumes were analyzed using multivariable linear regression models.
Results:
Compared with controls, R544C carriers WOCD had increased WMH volume, except in the occipital and midbrain areas, and showed a rapid increase in WMHs starting at age 48. They scored lower on the Mini-Mental State Examination (median = 28.4 vs 29.0, p = 0.048), Montreal Cognitive Assessment (MoCA) (median = 28.3 vs 29.0, p = 0.013), and memory and executive function tests than controls. After adjusting for age, sex, and education, MoCA scores were associated with whole-brain (r = -0.387, padj = 0.008) and regional WMHs (all padj < 0.05) except in the midbrain area. Age (β = 0.034, 95% CI 0.021-0.046, p < 0.001), hypercholesterolemia (β = 0.375, 95% CI 0.097-0.653, p = 0.009), and the vascular risk factor (VRF) index (β = 0.132, 95% CI 0.032-0.242, p = 0.019) were associated with the WMH severity in carriers.
Discussion:
Our study revealed that WMHs are extensively distributed in R544C carriers WOCD. They exhibited a rapid increase in WMHs beginning at age 48, approximately 7 years earlier than the reported age at symptomatic onset. Age was the strongest predictive factor of WMHs, and VRF, particularly hypercholesterolemia, might be modifying factors of WMHs.
More Related Videos
05:19A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis
Published on: November 22, 2024
09:38Generalized Psychophysiological Interaction PPI Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
