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British Medical Bulletin 42:42-50 (1986)
© 1986 The British Council

research-article

THE ASSOCIATION OF CLINICAL AND NEUROLOGICAL FINDINGS AND ITS BEARING ON THE CLASSIFICATION AND AETIOLOGY OF ALZHEIMER'S DISEASE

Sir Martin Roth

Department of Psychiatry, University of Cambridge

Abstract

Scientific observations recorded about Alzheimer's disease during the past decade exhibit a cohesion and convergence that have made it possible to trace many more associations between clinical and neurobiological phenomena than were previously possible. There is now evidence of neuronal loss from certain cortical regions, and plaques and tangles which show consistent negative correlations with a number of neurons so that these structural changes cannot be mere epiphenomena. Both structural and neurochemical lesions are highly selective, consistently affecting certain systems while leaving others intact. The frontal, temporal regions, cingulate gyrus and hippocampus are affected with a selective severity, and structural and neurochemical changes are correlated with each other and, in some instances, with measures of dementia. This sheds light on some of the clinical features, but leaves others unexplained. A threshold hypothesis is needed to explain some of the associations between clinical and pathological findings, and there is suggestive evidence that the situation may be analogous to that which obtains in relation to Parkinson's disease. A range of neurotransmitter deficits has been defined, the most severe being that affecting the cholinergic system. The early- and late-onset forms of the disorder are discriminated from each other by the nature of the cortical lesions, the range of neurotransmitter deficits and the neuronal outfall in a number of subcortical nuclei as well as certain clinical features, early cases being more severely affected in respect of each. This syndrome does not appear to be a parody of ageing but the late-onset group accords better though completely with such a hypothesis.


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