Clinical, Pathological and Neurochemical Characteristics of Lewy Body Dementia

Abstract

Dementia associated with Lewy bodies (LB), variously defined as Diffuse Lewy body disease, Senile Dementia of Lewy body type or Lewy body variant of Alzheimer’s disease (AD), may be the second most common cause of dementia after AD (Byrne, 1992; Crystal et al., 1990; Dickson et al., 1987; Förstl et al., 1993; Gibb et al., 1985; Hansen et al., 1990; Ikeda et al., 1980; Kosaka et al., 1984; Kuzuhara et al., 1988; Lennox et al., 1989; Mitsuyama et al., 1984; Okada et al., 1989; Perry et al., 1989; 1990). Retrospective survey, using newly defined clinical criteria (McKeith et al., 1992a) indicates that a proportion of Lewy body dementia (LBD) cases meet diagnostic criteria for AD and are likely to be inadvertently included in clinically defined AD categories. Pathological and neurochemical evidence suggests however that LBD is distinct from classical AD. Thus Lewy bodies are evident in cortical and subcortical areas and Alzheimer pathology is variable with cortical tangles often sparse or absent and little or no abnormally phosphorylated tau. Basal ganglia dopaminergic abnormalities include substantia nigra neuron loss together with reductions of dopamine [more apparent in caudate than putamen contrasting with Parkinson’s disease (PD)], which are likely to account for severe neuroleptic sensitivity in some cases (McKeith et al., 1992b). Neurochemically, cholinergic activities are lower and neocortical reductions more widespread in LBD than in AD, consistent with the more ‘anticholinergic’ nature of LBD symptoms including hallucinations or alterations in consciousness. Responders to cholinergic therapy are likely to include cases of LBD.