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Abstract
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 18fluorodopa (FDOPA), N-11C-methyl-4-piperidyl acetate (MP4A), and 18fluorodeoxyglucose (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.
Glossary
- AADC=
- aromatic acid decarboxylase;
- AChE=
- acetylcholine esterase;
- CMRglc=
- cerebral metabolic rate of glucose;
- DLB=
- dementia with Lewy bodies;
- FDG=
- 18fluorodeoxyglucose;
- FDOPA=
- 18fluorodopa;
- LB=
- Lewy bodies;
- LN=
- Lewy neurites;
- MMSE=
- Mini-Mental State Examination;
- MP4A=
- N-11C-methyl-4-piperidyl acetate;
- nbM=
- basal nucleus of Meynert;
- PD=
- Parkinson disease;
- PDD=
- Parkinson disease with dementia;
- PiB=
- Pittsburgh compound B;
- ROI=
- region of interest;
- SPM=
- statistical parametric mapping.
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