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).


CONCLUSIONS
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.
Ballard
C
C
Wolfson Centre for Age-Related Diseases, Wolfson Building, Guy's Campus, King's College London, London, SE1 1UL, UK. clive.ballard@kcl.ac.uk
Ziabreva
I
I
Perry
R
R
Larsen
J P
JP
O'Brien
J
J
McKeith
I
I
Perry
E
E
Aarsland
D
D
D000368:Aged; D000369:Aged, 80 and over; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D058225:Plaque, Amyloid / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D013702:Temporal Lobe / Q000201:enzymology / Q000473:pathology; D013997:Time Factors; D051844:alpha-Synuclein / Q000378:metabolism
D051844:alpha-Synuclein; D002795:Choline O-Acetyltransferase