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Title: The contributions of imaging biomarkers of subclinical cerebrovascular disease and Alzheimer's pathology to cognition in normal ageing
Author: Salarirad, Sima
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2011
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This thesis aimed to investigate the individual and combined effects of brain magnetic resonance imaging (MRI) markers of the two commonest age-related brain pathologies associated with dementia on longitudinal cognitive ability in normal ageing. Participants were 106 members of the Aberdeen 1921 Birth Cohort (ABC21), for whom childhood intelligence and serial measures of cognitive ability age 78-81 were available. Cerebrovascular disease was measured as white matter hyperintensities (WMH) at baseline (age 78-79) and over two successive time points; age 79-80 years and age 80-81 years using a visual scoring method. All participants had some WMH and these were most abundant in the frontal lobes. WMH increased in burden on followup and the greatest increase was seen in the parietal lobes, even allowing for participant drop-out, which was greater in those with more WMH at baseline. The effect of WMH on cognitive ability showed significant negative cross-sectional associations but there was no relationship between increase in WMH burden and longitudinal cognitive decline, either using linear regression analyses or latent growth curve modelling. Both WMH and childhood intelligence contribute significantly to late life fluid cognitive ability, but not to the trajectory of age-related change in fluid intelligence. Age was the strongest predictor of the cognitive trajectory from 78 to 81 years, even within the narrow age range of the ABC21 sample. Combined analysis of the influence of whole brain volume and WMH showed that the main predictor of dementia and death over 7 years follow-up of ABC21 was reduced viii brain fraction (< 73% of total brain volume normalised to intra-cranial volume). While WMH contributed to a diagnosis of dementia, they did not predict mortality. Comparison of manual and automated methods of hippocampal segmentation demonstrated that the automated method (FreeSurfer) systematically over-estimated volumes compared with a manual method (MRIcro) but that both methods were correlated. There were significant positive relationships between hippocampal volume and a variety of cognitive abilities, but these relationships were most significant for the left hippocampus. A final model of the influence of WMH (as a measure of cerebrovascular disease) and hippocampal volume (as a measure of Alzheimer‘s pathology) on lifelong cognitive change from age 11 to age 78 showed that both WMH and hippocampal volume had negative effects on late life fluid intelligence but that only the effect of hippocampal volume was significant. The conclusions of this work are that WMH are age-related and while they have a negative association with fluid intelligence, the main predictor of lifelong cognitive decline is hippocampal volume, an imaging marker of Alzheimer‘s pathology. The flowchart in next page is demonstrated a schematic summary of the thesis.
Supervisor: Not available Sponsor: Chief Scientist Office of the Scottish Government Health Directorates ; Millar MacKenzie Trust ; University of Aberdeen
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Brain