Grant: CIHR Fellowship

The role of small vessel disease (SVD) in cognition is well-known. SVD affects frontal-lobe functions (FF) most severely & its impact is exacerbated if there is prior brain vulnerability (eg. dementia pathology/atrophy). Yet, critical issues remain: 1) SVD is also present in normal cognition, suggesting a minimum threshold may be required for dysfunction. Such thresholds have been proposed but evidence suggests they are not sensitive to cognitive change. 2) It is unclear which specific FF processes are most vulnerable to SVD, because prior studies used composite measures despite evidence that they are not a unitary construct. 3) The impact of SVD on cognition may depend on the type of dementia, as each is associated with specific brain vulnerabilities which may modulate this relationship. We will address these issues using cognitive/imaging data from 1118 adults (50-95 years) with varying degrees of cognitive impairment & SVD, collected over 3 years at Sunnybrook. White matter hyperintensities (WMH), visible on T1 MR brain images, are used as a measure of SVD. Regional WMH volumes and brain atrophy are calculated using our in-house software, customized to segment tissues into grey/white matter & subtypes of SVD. We measure specific FF (Energization/Monitoring/Task Setting) using standard neuropsychological tests; 2 novel tests (given to a subset of 95 subjects) will help strengthen conclusions as aspects of these tests map reliably onto white-matter networks. We will determine 1) WMH thresholds associated with dementia over 3 years; 2) the impact of regional WMH volumes on Energization/Task Setting/Monitoring; 3) the strength of these associations in mild cognitive impairment, Alzheimer's dementia, Lewy body dementia, frontotemporal dementia & vascular dementia. Results will be crucial to develop ability-specific therapies for FF deficits, improve other areas of cognition downstream & disability-related outcomes, & guide dementia-specific interventions.