Using neuroimaging to understand cognitive impairment in patients with symptomatic carotid artery disease

Introduction Patients with symptomatic carotid artery disease have increased risk of cognitive impairment. Multiple mechanisms of cognitive impairment have been proposed. However, the contribution of each mechanism to cognitive impairment and the interrelation between these mechanisms remain unclear. Lesional and non-lesional damage of brain tissues may lead to cognitive impairment in patients with symptomatic carotid artery disease. The research presented aims to use whole brain statistical brain mapping and quantitative neuroimaging techniques to understand vascular cognitive impairment (VCI) in a group of patients with symptomatic carotid artery disease. Methods Studies presented in this thesis were based on available multimodal MRI and cognitive performance data from a study in patients with symptomatic carotid artery disease. Totally 108 subjects had FLAIR and diffusion MRI scans and 62 of them had resting-state fMRI scans in a 3T MRI scanner. All participants (n=108) underwent cognitive assessments using Addrenbrooke’s cognitive examination-revised (ACE-R). Voxel-based lesion symptom mapping (VLSM) technique was used to identify the contribution of ischaemic lesion presence to cognitive performance. Tract-based spatial statistics (TBSS) approach was used to investigate the association between microscopic damage of white matter and cognitive performance. Independent component analysis (ICA) and seed-based analysis approaches were used to investigate functional disconnection of large-scale cognitive networks and its contribution on cognitive impairment. The association between cognitive performance and ischaemic lesions volumes and microscopic damage of brain tissues were also assessed. Results The presence of chronic subcortical ischaemic lesions located in strategic white matter tracts including anterior thalamic radiation, forceps minor and forceps major contributed to global cognitive impairment in patients with symptomatic carotid artery disease. Ischaemic lesion volumes and microscopic damage of brain tissues including strategic brain areas, strategic white matter tracts, normal appearing white matter and white matter tract skeleton were related to cognitive impairment. Functional disconnection of large-scale cognitive networks including default mode network (DMN), dorsal attention network (DAN), left fronto-parietal network and salience network was found in patients with probable vascular mild cognitive impairment (VaMCI). Functional disconnection beyond the large-scale cognitive networks, showing as decreased functional connectivity between bilateral hippocampi, bilateral dorsal lateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) with the rest of the brain, was also found in patients with probable VaMCI. Also, the thesis presented preliminary results of the role of lesional and non-lesion brain damage in fluency performance in patients with symptomatic carotid artery disease. Conclusions This thesis provides further evidence for the role and to the nature of disconnection in VCI and proposes several disconnection related imaging biomarkers