Abstract
Degeneration of subcortical systems such as the dopaminergic nigrostriatal projection and the basal forebrain cholinergic corticopetal system as well as cortical neurodegeneration associated with depositions of α-synuclein and β-amyloid pathology are likely contributors to cognitive impairment in Parkinson disease (PD). Glucose metabolic studies have shown mixed subcortical and cortical changes in PD dementia. For example, incident dementia in idiopathic PD is heralded by decreased metabolism of visual association (Brodmann area 18) and posterior cingulate cortices with additional involvement of the caudate nucleus. Subsequent progression to dementia is associated with mixed subcortical, especially thalamic, and widespread cortical changes that involve the mesiofrontal lobes also. Neurotransmitter-specific PET imaging shows early and prominent nigrostriatal dopaminergic losses in PD, with no major differences in PD dementia. Therefore, caudate nucleus, limbic, and mesofrontal dopaminergic denervations do not appear alone sufficient for development of full-blown PD dementia. In contrast, cholinergic imaging studies have shown relatively mild losses in PD without dementia, but more prominent decreases in PD dementia. This suggests significant cholinergic pathology underlying progressive cognitive decline in PD. Average dopaminergic and cholinergic denervation does not appear to differ between PD with dementia (PDD) and dementia with Lewy bodies (DLB), supporting the view that PDD and DLB lie on a common disease spectrum. In vivo imaging studies show variable β-amyloid binding in PD dementia with prevalence of pathologic amyloid deposition higher in DLB compared to PDD. However, despite the relatively lower binding levels compared to AD, β-amyloid deposition contributes to cognitive impairment early in the course of cognitive decline in PD, suggesting a lower symptomatic threshold for the amyloid deposition compared to normal aging and Alzheimer disease (AD).
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Abbreviations
- AD:
-
Alzheimer disease
- DLB:
-
Dementia with Lewy bodies
- DTBZ:
-
Dihydrotetrabenazine
- FDG:
-
Fluorodeoxyglucose
- FDOPA:
-
6-Fluorodopa
- MP4A:
-
Methyl-4-piperidyl acetate
- PD:
-
Parkinson disease
- PDD:
-
Parkinson disease with dementia
- PET:
-
Positron emission tomography
- PMP:
-
Methyl-4-piperidinyl propionate
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Acknowledgments
The authors gratefully acknowledge research support from the NIH, the Department of Veterans Affairs, and the Michael J. Fox Foundation.
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Bohnen, N.I., Frey, K.A. (2014). Parkinson Dementia: PET Findings. In: Dierckx, R., Otte, A., de Vries, E., van Waarde, A., Leenders, K. (eds) PET and SPECT in Neurology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-54307-4_16
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