Neuropathology of dementia in Parkinson’s disease

Abstract

The neuropathology of Parkinson's disease dementia (PDD), like Parkinson's disease (PD), is heterogeneous, but most cases have Lewy-related pathology as the major pathologic substrate of parkinsonism. Less common causes of the PDD clinical syndrome include progressive supranuclear palsy and corticobasal degeneration. Most cases of PDD have diffuse cortical Lewy bodies, medial temporal neurofibrillary degeneration, and neocortical diffuse amyloid deposits. In most cases, Alzheimer-type pathology is not sufficient to warrant a diagnosis of Alzheimer's disease (AD). A subset of cases have concurrent AD, multiple cerebrovascular lesions consistent with vascular dementia, or severe pathology of the isodendritic core of cortically projecting subcortical nuclei with Lewy-related pathology that is relatively restricted to brainstem or limbic areas. Comparable degrees of Lewy-related and Alzheimer-type pathology are sometimes detected in subjects with PD without dementia, which suggests that there are other, yet to be determined, factors that are more proximal causes of cognitive impairment in PDD, such as synaptic loss, deficiencies of neurotransmitters, or the presence of soluble toxic oligomers of Aβ, tau or α-synuclein that lead to neuronal dysfunction.10 page(s