Neurotransmitter changes in dementia with Lewy bodies and Parkinson disease dementia in vivo.
OBJECTIVE
Although Parkinson disease with dementia (PDD) and dementia with Lewy bodies (DLB) show a wide clinical and neuropathologic overlap, they are differentiated according to the order and latency of cognitive and motor symptom appearance. Whether both are distinct disease entities is an ongoing controversy. Therefore, we directly compared patients with DLB and PDD with multitracer PET.


METHODS
PET with (18)fluorodopa (FDOPA), N-(11)C-methyl-4-piperidyl acetate (MP4A), and (18)fluorodeoxyglucose (FDG) was performed in 8 patients with PDD, 6 patients with DLB, and 9 patients with PD without dementia vs age-matched controls. Data were analyzed with voxel-based statistical parametric mapping and region of interest-based statistics.


RESULTS
We found a reduced FDOPA uptake in the striatum and in limbic and associative prefrontal areas in all patient groups. Patients with PDD and patients with DLB showed a severe MP4A and FDG binding reduction in the neocortex with increasing signal diminution from frontal to occipital regions. Significant differences between PDD and DLB were not found in any of the radioligands used. Patients with PD without dementia had a mild cholinergic deficit and no FDG reductions vs controls.


CONCLUSIONS
Patients with dementia with Lewy bodies and Parkinson disease dementia share the same dopaminergic and cholinergic deficit profile in the brain and seem to represent 2 sides of the same coin in a continuum of Lewy body diseases. Cholinergic deficits seem to be crucial for the development of dementia in addition to motor symptoms. The spatial congruence of cholinergic deficits and energy hypometabolism argues for cortical deafferentation due to the degeneration of projection fibers from the basal forebrain.
Klein
J C
JC
Department of Neurology, Goethe University, Frankfurt am Main, Germany.
Eggers
C
C
Kalbe
E
E
Weisenbach
S
S
Hohmann
C
C
Vollmar
S
S
Baudrexel
S
S
Diederich
N J
NJ
Heiss
W D
WD
Hilker
R
R
D000109:Acetylcholine / Q000378:metabolism*; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001931:Brain Mapping; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives; D004298:Dopamine / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D016631:Lewy Bodies / Q000000981:diagnostic imaging / Q000378:metabolism; D020961:Lewy Body Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods
D019788:Fluorodeoxyglucose F18; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D000109:Acetylcholine; D004298:Dopamine