Cerebellar atrophy in Alzheimer's disease - clinicopathological correlations

Morphometry of the cerebellum of 11 subjects who died in the severe, final stage of Alzheimer's disease (AD) and of five age-matched subjects without dementia revealed significant atrophy in the AD group, with a decrease in t he volume of the molecular layer by 24% and of the granular layer by 22% in comparison with controls. The 32% decrease in the total number of Purkinje cells that was observed correlates with the atrophy of the molecular layer , whereas the 30% reduction in the total number of granule cells correlates with the atrophy of the molecular and granular layers. A unique pattern of Alzheimer-type pathology was observed in the cerebellum: (1) there were no neurofibrillary changes in the cerebellum of either the control or the AD subjects, (2) there was almost the same extent of leptomeningeal and cortic al amyloid angiopathy in the normal aged subjects and in the AD patients, a nd (3) the presence of plaques was noted in the AD group, but not in the co ntrol group. This pattern of pathology suggests that two factors might be c onsidered in the etiopathogenesis of cerebellar atrophy: (1) transneuronal degeneration and neuronal loss resulting from primary pathologic changes in cerebral structures and (2) parenchymal cerebellar a-amyloidosis. The corr elation between the temporal duration of AD and both the decrease of the to tal number of granule cells (r = 0.86, p < 0.01) and the volumetric loss of the molecular (r = 0.73, p < 0.05) and granular (r = 0.93, p < 0.001) laye rs of the cerebellar cortex indicates that these cerebellar atrophic change s are likely to be related to the basic pathologic process of AD. Similarly , the correlation between the most complex parameter the atrophy of the cer ebellar cortex and the Functional Assessment Staging (FAST) measure of the clinical severity of AD at the time of demise (r = 0.63, p < 0.05) as well as with the duration of AD (r = 0.78, p < 0.01) indicates that cerebellar p athology, when viewed holistically, evolves continuously in association wit h clinical changes throughout the clinically manifest course of AD. (C) 199 9 Elsevier Science B.V. All rights reserved.