Executive function and CADASIL in MRI brain scans

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary and debilitating small vessel disease. One of the main features of CADASIL is progressive executive dysfunction, specifically problems in working memory, that ultimately leads to dementia. Due to the early-onset nature of the disease (symptomatic around 45 years old), CADASIL is often seen as a ‘pure’ model for small vessel diseases. In this thesis, I investigated working memory in CADASIL using a novel behavioral task that dissociated components of the working memory process. I also used structural and perfusion magnetic resonance imaging (MRI) to examine any differences associated with CADASIL. Finally, I investigated whether changes in the imaging metrics can predict working memory performance in CADASIL, both globally and within specific regions of interest, selected a priori. Nineteen CADASIL patients with nineteen healthy controls matched for age and sex ratio participated in this study. They completed a battery of neuropsychological assessments, including the novel behavioral task designed specifically to measure spatial working memory. The participants also completed an MRI brain scanning session on a 3T machine that included T1 structural imaging to measure grey matter volume and arterial spin labelling (ASL) perfusion imaging to quantify cerebral blood flow. From the behavioral task, I found significant decreases in spatial working memory in the CADASIL group, but their spatial binding ability appeared intact. The MR imaging modalities were analyzed using a general linear model for comparisons between the healthy controls and the CADASIL patients. Relative to the healthy controls, CADASIL patients showed significant grey matter atrophy in the medial and lateral frontal, and temporal regions, as well as extensive hypoperfusion encompassing the frontal, pre-frontal, anterior-occipital, parietal, and temporal lobes. Regions of grey matter atrophy and hypoperfusion included the dorsolateral prefrontal cortex, believed to be highly involved in spatial working memory, which suggested an association between brain integrity and behavioral metrics. Results presented in this thesis suggest a tight relationship between brain integrity and spatial working memory in the context of CADASIL. Furthermore, brain changes observed in CADASIL may help explain the observed deficits in one aspect of executive function - spatial working memory. These findings may contribute to a more complete understanding of executive function in CADASIL and may also help inform common features present in other small vessel diseases