Mapping neuromodulatory systems in Parkinson’s disease: lessons learned beyond dopamine

Zheng, Yuxiao

doi:10.1007/s44194-022-00015-w

Cited by 3 publications

(1 citation statement)

References 113 publications

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“…Recent brain imaging studies have provided insight into the dysfunction of multiple neuromodulatory studies that are involved in PD-CI. These were not limited to dopaminergic (DAergic) dysfunction but rather demonstrated the parallel alteration of DAergic, cholinergic and noradrenergic systems [ 323 ].…”

Section: Involvement Of Neuromodulatory Systems In Pd-cimentioning

confidence: 99%

Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks

Jellinger

2023

IJMS

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Cognitive impairment (CI) is a characteristic non-motor feature of Parkinson disease (PD) that poses a severe burden on the patients and caregivers, yet relatively little is known about its pathobiology. Cognitive deficits are evident throughout the course of PD, with around 25% of subtle cognitive decline and mild CI (MCI) at the time of diagnosis and up to 83% of patients developing dementia after 20 years. The heterogeneity of cognitive phenotypes suggests that a common neuropathological process, characterized by progressive degeneration of the dopaminergic striatonigral system and of many other neuronal systems, results not only in structural deficits but also extensive changes of functional neuronal network activities and neurotransmitter dysfunctions. Modern neuroimaging studies revealed multilocular cortical and subcortical atrophies and alterations in intrinsic neuronal connectivities. The decreased functional connectivity (FC) of the default mode network (DMN) in the bilateral prefrontal cortex is affected already before the development of clinical CI and in the absence of structural changes. Longitudinal cognitive decline is associated with frontostriatal and limbic affections, white matter microlesions and changes between multiple functional neuronal networks, including thalamo-insular, frontoparietal and attention networks, the cholinergic forebrain and the noradrenergic system. Superimposed Alzheimer-related (and other concomitant) pathologies due to interactions between α-synuclein, tau-protein and β-amyloid contribute to dementia pathogenesis in both PD and dementia with Lewy bodies (DLB). To further elucidate the interaction of the pathomechanisms responsible for CI in PD, well-designed longitudinal clinico-pathological studies are warranted that are supported by fluid and sophisticated imaging biomarkers as a basis for better early diagnosis and future disease-modifying therapies.

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Section: Involvement Of Neuromodulatory Systems In Pd-cimentioning

confidence: 99%

Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks

Jellinger

2023

IJMS

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The effects of L-DOPA on gait abnormalities in a unilateral 6-OHDA rat model of Parkinson's disease

Holden,

Venkatesh,

Budrow

et al. 2024

Physiology & Behavior

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Mild cognitive impairment in Parkinson's disease: current view

Jellinger

2024

Front. Cognit.

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Parkinson's disease (PD), the most common motor movement disorder and second most common neurodegenerative disorder after Alzheimer's disease (AD), is often preceded by a period of mild cognitive impairment (MCI), which is associated with impairment of a variety of cognitive domains including executive function, attention, visuospatial abilities and memory. MCI, a risk factor for developing dementia, affects around 30% of de novo PD patients and can increase to 75% after more than 10 years. While 30–40% remain in the MCI state, up to 60% will convert to dementia. Characteristic findings are slowing of EEG rhythms, frontotemporal hypoperfusion, decreased functional connectivity in the default mode and attentional networks, prefrontal and basal-ganglia-cortical circuits, which often manifests prior to clinical symptoms and overt brain atrophy. The heterogeneity of cognitive phenotypes suggests that a common neurodegenerative process affects multiple functional neuronal networks and neuromodulatory systems that may be superimposed by Lewy body and Alzheimer's-related or other co-pathologies. Sparse neuropathological data for PD-MCI revealed a heterogenous picture with various morphological changes similar to MCI in other diseases. This review highlights the essential epidemiological, clinical, neuroimaging and morphological changes in PD-MCI, available biomarkers, and discusses the heterogenous pathobiological mechanisms involved in its development. In view of its complex pathogenesis, well-designed longitudinal clinico-pathological studies are warranted to clarify the alterations leading to MCI in PD, which may be supported by fluid and neuroimaging biomarkers as a basis for early diagnosis and future adequate treatment modalities of this debilitating disorder.

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Mapping neuromodulatory systems in Parkinson’s disease: lessons learned beyond dopamine

Cited by 3 publications

References 113 publications

Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks

Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks

The effects of L-DOPA on gait abnormalities in a unilateral 6-OHDA rat model of Parkinson's disease

Mild cognitive impairment in Parkinson's disease: current view

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