Schott, Jonathan Mark; (2004) Short interval serial MRI studies in Alzheimer's disease and normal ageing. Doctoral thesis (M.D), UCL (University College London).

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Abstract

This thesis investigates rate of brain atrophy derived from serial volumetric magnetic resonance (MR) scans as a measure of progression in Alzheimer's disease (AD). Forty six patients with AD and 23 controls attended for multiple (7-10) MR brain scans and two serial neuropsychological and clinical assessments over one year; some subjects had additional scans at 18 months and two years. Techniques for accurate scan comparison (registration) and automated atrophy quantification (using the brain boundary shift integral - BBSI) were assessed. Atrophy determined using the BBSI was compared with manual measures of brain and ventricular change. Significant differences in atrophy rate between patients and controls were shown at intervals as short as six months. For each subject, the BBSI was used to calculate rate of whole brain atrophy from every possible scan pair; 2199 measurements were made for the patients, and 1182 for the controls. A multi-level model was used to determine mean atrophy rates (AD: 2.23%/year; controls: 0.49%/year) and inter- and intra-individual variances in rates for patients and controls. The improved precision of atrophy measurement made possible using the model was utilised to determine strategies for reducing sample sizes in clinical trials, and extended to determine factors both correlating with, and influencing, atrophy progression. Rate of cerebral atrophy was found to correlate with decline in a number of neuropsychological scores. Increasing disease severity, lower systolic blood pressure, and younger age at onset were found to predict subsequently increased rate of atrophy; the latter two factors appeared to be dependent on the former. An unbiased, longitudinal group analysis was used to determine brain areas undergoing significantly increased regional atrophy in AD. The pattern of regional atrophy was found to alter with disease progression, and further evidence for a relationship between systolic hypotension, age of onset and disease severity was demonstrated.

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