IC‐P‐092: Vascular brain lesions impair structural network efficiency in patients with early Alzheimer's disease

Abstract

Cerebrovascular lesions are suggested to promote the development of mild cognitive impairment (MCI) and Alzheimer's disease (AD).L acunar infarcts and white matter hyperintensities (WMH) may contribute to cognitive dysfunction by disrupting large-scale brain connectivity and thereby hamper information transfer between regions.We examined (1) whether vascular lesions are related to a less efficient structural brain network topology and (2) whether reduced global network efficiency is related to worse cognitive functioning in patients with early dementia. 51 patients (19 MCI, 23 AD, and 9 AD+vascular dementia, mean age 78 ± 7 years) were recruited via a memory clinic. All patients underwent a 3 Tesla MRI scan and cognitive assessment. Lacunar infarcts (yes/no) and WMH load were quantified using a visual rating scale. Brain volumes were automatically segmented and adjusted for intracranial volume. Di ffusion tensor imaging based tractography was used to reconstruct the brain network of each individual, followed by graph theoretical analyses. The number of fibers between two brain regions was taken as the strength of a connection. Overall network efficiency was assessed by measures of local (mean s trength, clustering coefficient) and global (path length) connectivity. Lacunar infarcts were present in 53% of patients with MCI, 22% of patients with AD, and 56% of patients with AD+vascular dementia. WMH load did not differ between patient groups. Across all patients, the presence of lacunar infarcts and a higher WMH load were associated with reduced strength, increased path length, and decreased clustering coefficient of the network (P <0.05, Table 1 upper panel), indicating reduced brain connectivity in patients with cerebrovascular disease. These associations remained significant after adjusting for dementia diagnosis, total brain volume, and after normalizing the total number of fibers in the network. Less efficient network properties were associated with poorer performance on tests of information processing speed, attention, and memory (P <0.05, Table 1 lower panel). Visualization of brain network reconstructed for each subject. Each sphere (node) represents a brain region according to a standardized template. The size and color of the nodes represent the centrality of that region within the network. The opacity of the connections between brain regions (edges) represents the number of tracts or the ‘strength’ of the connection. Vascular lesions were related to less efficient structural brain network topology in patients with early dementia. Disruption of large-scale brain connectivity by vascular lesions may contribute to the development of cognitive impairment.