Differences in neuropathologic characteristics across the Lewy body dementia spectrum

Background: The objective of this comparative neuropathologic study was to determine the extent to which dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD) are distinct entities or part of a continuum with respect to the duration of parkinsonism. Methods: We evaluated the relationship between cortical alpha-synuclein pathology, plaques (Consortium to Establish a Registry for Alzheimer's Disease [CERAD]), tangles (Braak staging), and cholinergic deficits ( choline acetyltransferase in temporal cortex) in 57 prospectively assessed patients ( 29 DLB, 28 PDD), confirmed at autopsy. The PDD group was divided according to the median duration of parkinsonism prior to dementia. Results: There was an association between longer duration of parkinsonism prior to dementia and less severe cortical alpha-synuclein pathology (chi(2) 10.4, df 2, p = 0.006) and lower CERAD plaque scores (chi(2) 26.6, df 9, p = 0.002), but not Braak staging. These findings were confirmed in a further correlation analysis, which also identified an unexpected correlation between more pronounced cortical cholinergic deficits and longer duration of parkinsonism prior to dementia (R = -0.37, p = 0.04). Conclusion: While there is a clear relationship between the duration of Parkinson disease prior to the onset of dementia and key neuropathologic and neurochemical characteristics, there is a gradation of these differences across the dementia with Lewy bodies/Parkinson disease dementia spectrum and the findings do not support an arbitrary cut-off between the two disorders.