Abstract
Ischemic leukoaraiosis (ILA) is related to cognitive impairment and vascular dementia in the elderly. One possible mechanism could be the disruption of white matter (WM) tracts and network function that connect distributed brain regions involved in cognition. The purpose of this study was to investigate the relationship between structural connectome and cognitive functions in ILA patients. A total of 89 patients with ILA (Fazekas score ≥ 3) and 90 healthy controls (HCs) underwent comprehensive neuropsychological examinations and diffusion tensor imaging scans. The tract-based spatial statistics approach was employed to investigate the WM integrity. Graph theoretical analysis was further applied to construct the topological architecture of the structural connectome in ILA patients. Partial correlation analysis was used to investigate the relationships between network measures and cognitive performances in the ILA group. Compared with HCs, the ILA patients showed widespread WM integrity disruptions. The ILA group displayed increased characteristic path length (Lp) and decreased global network efficiency at the level of the whole brain relative to HCs, and reduced nodal efficiencies, predominantly in the frontal–subcortical and limbic system regions. Furthermore, these structural connectomic alterations were associated with cognitive impairment in ILA patients. The association between WM changes (i.e., fractional anisotropy and mean diffusivity measures) and cognitive function was mediated by the structural connectivity measures (i.e., local network efficiency and Lp). In conclusion, cognitive impairment in ILA patients is related to microstructural disruption of multiple WM fibers and topological disorganization of structural networks, which have implications in understanding the relationship between ILA and the possible attendant cognitive impairment.
Highlights
MATERIALS AND METHODSIschemic leukoaraiosis (ILA), referred to as white matter hyperintensities (WMHs) or age-related white matter (WM) changes, is characterized by bilateral, patchy, or diffuse areas of hyperintensities with different severity on T2-weighted or fluid-attenuated inversion recovery (FLAIR) sequence in the elderly (Wardlaw et al, 2013; Prins and Scheltens, 2015; Alber et al, 2019)
In the ILA group, cognitive function in cognitive domain episodic memory, information processing speed, and executive function were significantly worse than healthy controls (HCs)
Our main results are as follows: (1) WM tract integrity was extensively disrupted in ILA patients as indicated by significantly reduced fractional anisotropy (FA) in several fiber bundles including the corpus callosum (CC), EC.L, bilateral anterior limb of internal capsule (ALIC), anterior corona radiata (ACR), posterior corona radiata (PCR), posterior thalamic radiation (PTR), superior fronto-occipital fasciculus (SFOF), and tapetum; (2) the global topological organization of WM structural networks in ILA patients was significantly disrupted as indicated by abnormal small-world properties and topological efficiency; (3) the regional characteristics were reduced predominantly in the frontal–subcortical and limbic system areas in ILA patients; (4) these structural connectomic alterations correlated with the cognitive performances in the ILA group; and (5) the relationship between WM abnormalities (i.e., FA and mean diffusivity (MD) measures) and domain-specific cognitive function was mediated by the structural connectivity measures
Summary
MATERIALS AND METHODSIschemic leukoaraiosis (ILA), referred to as white matter hyperintensities (WMHs) or age-related white matter (WM) changes, is characterized by bilateral, patchy, or diffuse areas of hyperintensities with different severity on T2-weighted or fluid-attenuated inversion recovery (FLAIR) sequence in the elderly (Wardlaw et al, 2013; Prins and Scheltens, 2015; Alber et al, 2019). Increasing evidences have confirmed that cognitive function is strongly associated with WM integrity detected by DTI (Li et al, 2012; Chen et al, 2020). As reported previously based on the tract-based spatial statistics (TBSS) technique, the atrophy and reduced diffusion anisotropy of the corpus callosum (CC) may indicate diffuse deep WM destruction in ILA, which may explain global cognitive decline and progression of vascular dementia (Otsuka et al, 2012). Many studies have revealed that fractional anisotropy (FA) and mean diffusivity (MD) are sensitive indices for use in evaluating their relationships with cognitive impairment in ILA patients (Della Nave et al, 2007).
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