Dementia in Parkinson's disease: characterization of transmitter deficits

Background: Up to 40% of patients with Parkinson's disease (PD) develop dementia. However, the neurochemical deficit underlying the cognitive decline in these patients is still under debate. To evaluate the contribution of different transmitter systems, PD patients with and without dementia were examined by multitracer PET imaging.

Patients and Methods: In 17 non-demented patients with PD (mean age 61.8±8.7 years, mean MMSE score 27.9±1.8 points) and 10 PD patients with dementia (PD-D; 64± 8.1 years, MMSE score 21.0±5.7), PET of cerebral glucose metabolism (rCMRGlc; 18FDG), acetylcholine-esterase (AChE) activity (11C-MP4A) and dopaminergic function (18FDOPA) were performed. Data were compared to a total of 42 age-matched normal controls (62.5±7.0 years) with SPM99.

Results: In PD and PD-D, the striatal 18FDOPA uptake was significantly reduced without differences between both groups. In PD-D, widespread significant decreases of AChE activity were detected, in particular bilaterally in the frontal cortex (BA9, 10), the left temporal (BA19) and both parietal lobes. In contrast, PD patients showed solely restricted areas with lower cholinergic activity in both occipital (BA17, 18, 19) and the left parietal lobe (BA40). Corresponding to decreased AChE activity, PD-D subjects revealed significant rCMRGlc reductions in both frontal (BA 8, 9) and the left temporal lobe (BA 7, 40), whereas rCMRGlc in PD patients was normal. In the PD-D group, covariance analysis proved significant relations between putaminal FDOPA uptake reduction and widespread frontal and temporo-parietal reduction of AChE activity.

Conclusion: PD-D patients revealed more widespread and severe cholinergic dysfunction than PD patients without dementia. Cholinergic depletion also comprised fronto-temporal regions relevant for cognitive function. Cortical glucose metabolism was remarkably less reduced than cholinergic activity indicating a specific transmitter defect rather than general neuronal atrophy in PD-D. Striatal dopaminergic dysfunction was not different in PD-D patients compared to those without dementia and, therefore, does not seem provide to a sufficient explanation of dementia development in PD. In PD-D, the strong coincidence of dopaminergic and cholinergic deficits suggests a pathophysiological link between the degenerative processes in both transmitter systems.