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Title: Brain white matter hyperintensities : correlates in normal ageing and relevance in Alzheimer's disease
Author: Murray, Alison D.
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2012
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White matter hyperintensities (WMH) on brain MRI are commonly seen in normal older people. The influence of WMH on cognitive ageing is measured in the Aberdeen Birth Cohorts of 1921 and 1936. The effect of WMH and hypertension on life-long cognitive ageing is modelled from childhood to late life. The positive influence of childhood intelligence decreases with age and the negative influence of WMH increases. The negative effect of hypertension is all mediated by WMH. In a model including WMH and hippocampal volume, the negative effect of these subclinical markers of vascular and Alzheimer's diseases (AD) respectively, is balanced by the positive influence of educational attainment, which provides cognitive reserve. In a comparison of ABC samples with AD patients, there is no difference in WMH burden, but hippocampal volumes and cognitive ability are significantly lower in AD. In ABC36, deep brain lesions predict depressive symptoms, however, the main predictor is lower fluid intelligence. In a model investigating the influence of lesion location on cognitive, physical and depressive symptom outcomes, there is no direct effect on depressive symptoms. Deep brain lesions predict poorer physical and cognitive ability. Supratentorial lesions predict poorer cognitive ability. Socioeconomic circumstance in childhood (cSEC) in ABC36 is estimated from paternal occupation. The influence of cSEC on total and regional WMH is modelled, accounting for sex, childhood intelligence and education. A gradient of increasing brain hyperintensities with greater cSEC disadvantage is found, most significant for hemispheric WMH, where there is a step-change between clerical-manual paternal occupation. This effect is not removed by higher adult SEC and is greater than the effect of hypertension. Poor SEC in early life results in more WMH and such individuals probably lack the resilience to adverse effects on cognitive decline, physical frailty and depressed mood provided by higher intelligence and prolonged education.
Supervisor: Not available Sponsor: Roland Sutton Academic Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Brain ; Children