Cortical Lewy body pathology in the diagnosis of dementia

Dementia with Lewy bodies (DLB) and Parkinson's disease (PD) are distinguis hable clinically but often ten not neuropathologically. This study aims to test whether the distribution of cortical Lewy bodies differs in these clin icopathological groups and to develop diagnostic protocols for their differ entiation. Brains were obtained at autopsy from cases recruited from prospe ctive clinical studies of dementia or movement disorders. All cases with si gnificant pathologies other than Lewy bodies or plaques were excluded. Case s were categorised into either PD without dementia, DLB (dementia first or within 2 years of disease onset), or PD with a later onset of dementia (PDD ). The distribution and density of Lewy bodies and Lewy neurites was determ ined using antibodies to ubiquitin and alpha -synuclein. Cortical Lewy body densities could not separate cases of DLB from those with PDD. However, se miquantitative thresholds in the parahippocampus could separate demented fr om non-demented cases with high sensitivity and specificity. Interactions b etween multiple pathologies were determined using factor analysis. Although many cases had CA2 Lewy neurites, this was not associated with severity or duration of either dementia or parkinsonism. Most DLB cases had significan t plaque pathology, and severity and duration of dementia was related to bo th increasing parahippocampal Lewy body densities and neuritic plaque grade . Weighted kappa statistics revealed that the combination of these patholog ies indicated a more severe dementia. These results suggest that dual patho logies cause DLB, and high densities of parahippocampal Lewy bodies indicat e dementia regardless of additional pathologies.