Brain atrophy in normal ageing and Alzheimer's disease. Volumetric discrimination and clinical correlations.

BACKGROUND: We examined the differences in volume of the ventricular and extracerebral cerebrospinal fluid spaces in normal ageing and in probable Alzheimer's disease (AD) and we tried to investigate the effects of the severity of illness on the morphometric differentiation of AD and ageing, the principal components underlying brain atrophy in both conditions, and the correlations of these measurements with clinical findings.
METHOD: Forty patients with probable AD were matched with 40 non-demented elderly controls. Both groups underwent standardised clinical tests and unenhanced cranial computed tomography for post hoc volumetric analysis.
RESULTS: The lateral and third ventricles and the anterior and lateral fissures were significantly larger in AD than in normal ageing. The volumes of the lateral ventricle and lateral fissure permitted a highly efficient differentiation between normal ageing and AD even at the mild stage of dementia, and this differentiation was improved further in the more severe stages of illness. We identified one principal component underlying brain atrophy in normal ageing and two components in AD: a 'grey matter' component accounting for sulcal and third ventricular enlargement, and a 'white matter' component for lateral ventricular enlargement. In AD, most of the volumetric measurements were significantly correlated with cognitive impairment, but in the group of non-demented elderly controls they were correlated with age. CONCLUSION. Volumetric indices of brain atrophy permit a highly efficient differentiation between normal ageing and AD even in the mild stages of illness and this demonstrates that substantial structural brain changes have developed in the preclinical phase of illness. We suggest that there is an uncoupling between lateral ventricular enlargement and cortical brain atrophy in AD.