TY - JOUR
T1 - Cerebral microinfarcts affect brain structural network topology in cognitively impaired patients
AU - Zhang, Liwen
AU - Biessels, Geert Jan
AU - Hilal, Saima
AU - Chong, Joanna Su Xian
AU - Liu, Siwei
AU - Shim, Hee Youn
AU - Xu, Xin
AU - Chong, Eddie Jun Yi
AU - Wong, Zi Xuen
AU - Loke, Yng Miin
AU - Venketasubramanian, Narayanaswamy
AU - Yeow, Tan Boon
AU - Chen, Christopher Li-Hsian
AU - Zhou, Juan Helen
N1 - Funding Information:
The authors acknowledge all participants for their contribution to this study, and their colleagues at the Clinical Imaging Research Centre, National University of Singapore for their help with data collection. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was funded by the National Medical Research Council (NMRC) Centre Grant (NMRC/CG/013/2013 and NMRC/CG/NUHS/2010 to Dr. Christopher Chen), the Biomedical Research Council, Singapore (BMRC 04/1/36/372 to Dr Juan Zhou), the National Medical Research Council, Singapore (NMRC/CBRG/0088/2015, NMRC/CIRG/1390/2014 to Dr Juan Zhou, and NMRC/CIRG/1446/2016 to Dr Christopher Chen), and Duke-NUS Medical School Signature Research Program funded by Ministry of Health (to Dr Juan Zhou), Singapore.
Publisher Copyright:
© The Author(s) 2020.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2021/1
Y1 - 2021/1
N2 - Cerebral microinfarcts (CMIs), a novel cerebrovascular marker, are prevalent in Alzheimer’s disease (AD) and associated with cognitive impairment. Nonetheless, the underlying mechanism of how CMIs influence cognition remains uncertain. We hypothesized that cortical-CMIs disrupted structural connectivity in the higher-order cognitive networks, leading to cognitive impairment. We analyzed diffusion-MRI data of 92 AD (26 with cortical-CMIs) and 110 cognitive impairment no dementia patients (CIND, 28 with cortical-CMIs). We compared structural network topology between groups with and without cortical-CMIs in AD/CIND, and tested whether structural connectivity mediated the association between cortical-CMIs and cognition. Cortical-CMIs correlated with impaired structural network topology (i.e. lower efficiency/degree centrality in the executive control/dorsal attention networks in CIND, and lower clustering coefficient in the default mode/dorsal attention networks in AD), which mediated the association of cortical-CMIs with visuoconstruction dysfunction. Our findings provide the first in vivo human evidence that cortical-CMIs impair cognition in elderly via disrupting structural connectivity.
AB - Cerebral microinfarcts (CMIs), a novel cerebrovascular marker, are prevalent in Alzheimer’s disease (AD) and associated with cognitive impairment. Nonetheless, the underlying mechanism of how CMIs influence cognition remains uncertain. We hypothesized that cortical-CMIs disrupted structural connectivity in the higher-order cognitive networks, leading to cognitive impairment. We analyzed diffusion-MRI data of 92 AD (26 with cortical-CMIs) and 110 cognitive impairment no dementia patients (CIND, 28 with cortical-CMIs). We compared structural network topology between groups with and without cortical-CMIs in AD/CIND, and tested whether structural connectivity mediated the association between cortical-CMIs and cognition. Cortical-CMIs correlated with impaired structural network topology (i.e. lower efficiency/degree centrality in the executive control/dorsal attention networks in CIND, and lower clustering coefficient in the default mode/dorsal attention networks in AD), which mediated the association of cortical-CMIs with visuoconstruction dysfunction. Our findings provide the first in vivo human evidence that cortical-CMIs impair cognition in elderly via disrupting structural connectivity.
KW - Alzheimer’s disease
KW - cognitive impairment
KW - cognitive impairment no dementia
KW - cortical cerebral microinfarcts
KW - structural network topology
UR - http://www.scopus.com/inward/record.url?scp=85078422882&partnerID=8YFLogxK
U2 - 10.1177/0271678X20902187
DO - 10.1177/0271678X20902187
M3 - Article
C2 - 31986957
SN - 0271-678X
VL - 41
SP - 105
EP - 115
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 1
ER -