The potential role of leukoaraiosis in remodeling the brain network to buffer cognitive decline: a LADIS study from ADNI

Background Leukoaraiosis (LA) is a phenomenon of the brain that is often observed in elderly people. However, little is known about the role of LA in cognitive impairment in neurodegeneration and disease. This cross-sectional, retrospective Leukoaraiosis And Disability (LADIS) study aimed to characterize the relationship between brain white matter connectivity properties with LA ratings in patients with Alzheimer's disease (AD) as compared with age-matched cognitively normal controls. Methods Patients with AD (n=76) and elderly individuals with normal cognitive (NC) function (n=82) were classified into 3 groups, LA1, LA2, and LA3, according to the rating of their white matter changes (WMCs). Diffusion tensor imaging (DTI) data were analyzed by quantifying and comparing the white matter connectivity properties and gray matter (GM) volume of brain regions of interest (ROIs). Results The rich-club network properties in the AD LA1 and LA2 groups showed significant patterns of disrupted peripheral regions and reduced connectivity compared to those in the NC LA1 and LA2 groups, respectively. However, the rich-club network properties in the AD LA3 group showed similar patterns of disrupted peripheral regions and reduced connectivity compared to those in the NC LA3 group, despite there being significant hippocampal and amygdala atrophic differences between AD patients and NC elders. Compared to the NC LA1 group, the characteristic path length of white matter fiber connectivity in the NC LA3 group was significantly increased, and the brain's global efficiency, clustering coefficient, and network connectivity strength were significantly reduced (P 0.05) were observed in characteristic path length, reduced global efficiency, or the clustering coefficient between the NC LA3 and AD LA1 groups, or between the NC LA3 and AD LA2 groups. Conclusions Our findings offer some insights into a potential role of LA in cognitive impairment that may predict the development of disability in older adults. The occurrence of LA, an intermediate degenerative change, during neurodegeneration and disease may potentially lead to the remodeling of the brain network through brain plasticity. LA, therefore, representing a possible compensatory mechanism to buffer cognitive decline.