Abstract
To determine whether white matter network disruption mediates the association between MRI markers of cerebrovascular disease (CeVD) and cognitive impairment. Participants (n = 253, aged ≥60 years) from the Epidemiology of Dementia in Singapore study underwent neuropsychological assessments and MRI. CeVD markers were defined as lacunes, white matter hyperintensities (WMH), microbleeds, cortical microinfarcts, cortical infarcts and intracranial stenosis (ICS). White matter microstructure damage was measured as fractional anisotropy and mean diffusivity by tract based spatial statistics from diffusion tensor imaging. Cognitive function was summarized as domain-specific Z-scores.
Lacunar counts, WMH volume and ICS were associated with worse performance in executive function, attention, language, verbal and visual memory. These three CeVD markers were also associated with white matter microstructural damage in the projection, commissural, association, and limbic fibers. Path analyses showed that lacunar counts, higher WMH volume and ICS were associated with executive and verbal memory impairment via white matter disruption in commissural fibers whereas impairment in the attention, visual memory and language were mediated through projection fibers.
Our study shows that the abnormalities in white matter connectivity may underlie the relationship between CeVD and cognition. Further longitudinal studies are needed to understand the cause-effect relationship between CeVD, white matter damage and cognition.
Lacunar counts, WMH volume and ICS were associated with worse performance in executive function, attention, language, verbal and visual memory. These three CeVD markers were also associated with white matter microstructural damage in the projection, commissural, association, and limbic fibers. Path analyses showed that lacunar counts, higher WMH volume and ICS were associated with executive and verbal memory impairment via white matter disruption in commissural fibers whereas impairment in the attention, visual memory and language were mediated through projection fibers.
Our study shows that the abnormalities in white matter connectivity may underlie the relationship between CeVD and cognition. Further longitudinal studies are needed to understand the cause-effect relationship between CeVD, white matter damage and cognition.
| Original language | English |
|---|---|
| Pages (from-to) | 1858-1872 |
| Number of pages | 15 |
| Journal | Journal of Cerebral Blood Flow and Metabolism |
| Volume | 41 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2 Feb 2021 |
Bibliographical note
Funding Information:The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The Epidemiology of Dementia in Singapore study is supported by the National Medical Research Council (NMRC), Singapore (NMRC/CG/NUHS/2010 [Grant no: R-184-006-184-511]), (NMRC/CSA/038/2013) and Bight Focus Foundation [R?608?000?248?597]. The research conducted in this study is also supported by the National Medical Research Council, Singapore (NMRC0088/2015), the Duke-NUS Medical School Signature Research Program funded by Ministry of Health, Singapore, and Center for Sleep and Cognition funded by Yong Loo Lin School of Medicine, National University of Singapore.
Publisher Copyright:
© The Author(s) 2021.