A modern hypothesis: The distinct pathologies of dementia associated with Parkinson's disease versus Alzheimer's disease.

BACKGROUND/AIMS Parkinson's disease dementia (PDD) is common, but its neuropathological basis has been controversial. The aim of this review was to survey the recent literature on the pathology of PDD and compare the pathology of PDD to that of Alzheimer's disease (AD). METHODS A literature search was performed to identify relevant research published since 2001. RESULTS There is widespread Lewy body pathology in the neocortex and subcortical regions in PDD, and Lewy neurites in the CA2 region of the hippocampus that correlate with cognitive decline. Genetic forms of PD, which frequently lead to dementia, are associated with deposition of alpha-synuclein; PDD is not related to the apolipoprotein E epsilon 4 genotype. Compared with AD, central cholinergic deficits occur earlier, are greater and more widespread in PDD, but PDD can occur without the abundant senile plaques and neurofibrillary tangles indicative of AD. CONCLUSION Epidemiological investigations, neuroimaging, as well as genetic and neuropathological studies increasingly support PDD as distinct from AD.