Neuropathological distinction between Parkinson's dementia and Parkinson's plus Alzheimer's disease

The distinctive clinical features of dementia in Parkinson's disease (PDD) and Parkinson's plus Alzheimer's disease (PD + AD) suggest different patterns of cerebral atrophy in these conditions. To determine the pathoanatomical substrates of dementia in PDD and PD + AD, morphometric analysis of 5 standardized coronal slices was used to identify volumetric changes in cerebral tissue. In PDD (n = 4) there were 9 to 23% reductions in cross-sectional area of cerebral cortex, a 38% loss of tissue in the globus pallidus + putamen, and an 18% reduction in area of the amygdala, whereas in PD + AD (n = 6) there was severe global atrophy of the cerebral cortex (27-29% reductions), moderate atrophy of white matter (10-19% reductions), and 40% reductions in areas of globus pallidus + putamen and the amygdala relative to neuropathologically intact controls (n = 14). Immunostaining with anti-glial fibrillary acidic protein disclosed significant gliosis of all four major subdivisions of neocortex in PD + AD and gray matter of the caudate, putamen, globus pallidus, and thalamus in both PDD and PD + AD relative to controls. The findings suggest that dementia in PDD is mainly subcortical in origin and due to neuronal degeneration in basal ganglia, the amygdala, and thalamus. In PD + AD the same pattern and degree of subcortical degeneration is evident, but there are clearly superimposed lesions involving cortical neurons and long projection fibers coursing through cerebral white matter that most likely account for the distinctive manifestations of dementia in this condition compared with PDD.