Neuropathology and pathogenesis of dementia with lewy bodies

Dementia with Lewy bodies (DLB) is a clinical syndrome characterized by mid-to-late life dementia associated with visual hallucinations, parkinsonism and a fluctuating clinical course (McKeith et al, 2004). In this discussion, the term Lewy body disease (LBD) is used to refer to the pathological process associated with neuronal cytoplasmic inclusions first described by Lewy (Dickson, 2002a). As is true for all clinical neurological syndromes, the pathological substrate of DLB is not exclusively a single disease process. For example, parkinsonism, which is the clinical syndrome characterized by bradykinesia, rigidity and resting tremor, has a number of distinct pathological substrates, including LBD, multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) (Dickson, 2002b). These disorders share progressive neuronal loss and gliosis in the dopaminergic neurons of the pars compacta of the substantia nigra, which leads to the striatal dopaminergic deficiencies that cause the extrapyramidal parkinsonian syndrome (Fig. 11.1c). Given that one of the cardinal clinical features of DLB is parkinsonism, it can be predicted that the pathological substrate for this aspect of DLB might be heterogeneous. Indeed, autopsy studies of prospectively diagnosed patients with DLB occasionally have identified neurofibrillary tangle pathology, consistent with PSP, in the substantia nigra rather than Lewy bodies (McKeith et al, 2000).