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Title: Investigating mechanisms of cognitive decline in patients with cerebral small vessel disease using a combination of neuropsychology and advanced MRI techniques
Author: Zeestraten, Eva Anna
ISNI:       0000 0004 6350 6690
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2016
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Aims: To investigate the potential of neuro imaging parameters, including those derived from diffusion tensor imaging (DTI), as surrogate markers of cerebral small vessel disease (SVD), by determining their sensitivity to SVD progression and relationship to cognitive impairment. Methods: A group of 121 patients with symptomatic SVD were assessed on a range of neuropsychological tests and multimodal magnetic resonance imaging (MRI) techniques in the prospective St George’s Cognition And Neuroimaging in Stroke study. MRI was acquired annually for 3 years to evaluate brain volume, lacune and cerebral microbleed number, white matter hyperintensity (WMH) volume, and white matter (WM) micro structural damage. Neuropsychological testing was performed annually for a period of 5 years and assessed cognitive abilities in various cognitive domains. Results: Longitudinal analyses revealed that over a period of 5 years significant declines could be observed in EF, PS and global functioning whilst memory functions remained preserved (Chapter 4). However, all MRI markers, particularly brain volume, WMH lesion load (Chapter 5) and DTI parameters (Chapter 7), were much more sensitive to change than the investigated cognitive measures. These MRI parameters therefore had the smallest sample size estimates for hypothetical clinical trials. The progression rate of WM microstructural deterioration, and presence of new lacunes together predicted longitudinal change in cognition (executive and global function) (Chapter 8). New lacunes were associated with gender and diastolic blood pressure, and preferentially developed at the edge of WMH where they were gradually incorporated in expanding WMH (Chapter 6). Progression to dementia could be predicted by a combination of WM microstructural deterioration and WMH growth (Chapter 8). Conclusions: This study provides support for the use of MRI parameters, particularly those derived from DTI, as surrogate markers of SVD. Their use could significantly reduce the size, cost and duration of clinical trials screening treatment efficacy in SVD.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available