A number of chronic disease and behavioural factors are recognised to increase the risk of cardiovascular and cerebrovascular diseases. These putative ???vascular??? risk factors have increasingly been recognised to increase the risk of cognitive impairment in the absence of clinically manifest ischemic events. Their relationship to structural brain changes has received limited attention. In this dissertation, I used high resolution magnetic resonance image (MRI) to examine two structural features of the brain, regional gray matter (GM) volumes and silent lacunar infarcts, and determined their association with vascular risk factors. I related these to cognitive function in both cross-sectional and longitudinal studies. The work was based on the data of three waves in two healthy cohorts drawn from the PATH Through Life Study, which is a population-based longitudinal study of ageing comprising 3 cohorts aged 20-24, 40-44, and 60-64 years, with about 2500 participants in each cohort. Random subsamples of Wave 1 of the cohort aged 60-64 years (N = 478) and Wave 2 of the 40+ cohort (aged 44-48 years) (N = 411) were examined cross-sectionally for the MRI sub-study. The MRI cohort aged 60-64 years was re-examined 4 years later in Wave 2. These studies showed that vascular risk factors are associated with lower regional GM volumes and this association varies at different ages. In adults aged 44-48 years, individual risk factors did not show a significant relationship with GM volumes, but the Framingham risk score was associated with less GM volumes in a number of brain regions, suggesting an additive effect of the risk factors. In the 60+ cohort, hypertension was independently associated with less regional GM volumes in bilateral medial frontal, right superior frontal, left superior temporal and precentral gyri. The same cohort, when examined in Wave 2, showed the negative association of hypertension with gray matter volumes to be more widespread. These associations were observed in men but not in women in either wave. Sex dimorphism was observed in the younger cohort as well, with greater GM volumes in temporal and occipital cortices, midbrain and cerebellum in men, while less GM volumes in cingulate and parietal cortices in comparison with women. Lacunar infarcts were present in 7.8 % of the 60+ cohort, and asymptomatic new lacunar lesions developed in 0.4 % per year in this group. The prevalence of lacunar infarcts was correlated with hypertension and a steeper decline in mental speed. These series of studies indicate the relationship of vascular risk factors with changes in brain structure and cognitive function in healthy middle-aged adults. It is suggested that modifying these vascular risk factors may protect the brain from silent lesions and cognitive impairment, and that intervention should begin early in life to have a major impact.
| Identifer | oai:union.ndltd.org:ADTP/187535 |
| Date | January 2007 |
| Creators | Chen, Xiaohua, Psychiatry, Faculty of Medicine, UNSW |
| Publisher | Awarded by:University of New South Wales. Psychiatry |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | Copyright Xiaohua Chen, http://unsworks.unsw.edu.au/copyright |
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