Cholinergic Dysfunction in Parkinson’s Disease

Müller, Martijn; Bohnen, Nicolaas I.

doi:10.1007/s11910-013-0377-9

Cited by 217 publications

(147 citation statements)

References 97 publications

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“…During later phases of the disease, other signs and symptoms emerge, specifically gait and balance problems, and cognitive impairments. It is widely believed that balance problems are the result of degeneration in the portion of the PPN that belongs to the mesencephalic locomotor region and/or degeneration of cholinergic cell groups [e.g., 90,[133][134][135][136][137][138][139]. Cognitive impairments are likely caused by a combination of factors, including the extension of significant dopamine loss to nonmotor portions of the basal ganglia, and the spread of pathology to prefrontal cortical regions [132].…”

Section: Pathophysiology Of Parkinsonism and Dystoniamentioning

confidence: 99%

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

2016

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Deep brain stimulation (DBS) is highly effective for both hypo-and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal gangliathalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks.

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Section: Pathophysiology Of Parkinsonism and Dystoniamentioning

confidence: 99%

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

2016

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“…29 Cholinergic dysfunction assessed with this technique is also associated with impaired postural and olfactory function, and rapid-eyemovement sleep behaviour disorder. 30 PET has also been used to detect widespread reductions in nicotinic acetylcholine receptor binding in Parkinson's disease, which could relate to depressive (cingulate and occipital cortex, putamen, and midbrain) and cognitive (midbrain, pons, and cerebellum) features. 31 Far fewer studies have been done on other neuro-transmitters in Parkinson's disease than on the monoamines and cholinergic systems.…”

Section: Non-dopaminergic Changes and Non-motor Complications In Parkmentioning

confidence: 99%

Imaging insights into basal ganglia function, Parkinson's disease, and dystonia

Stoessl¹,

Lehericy²,

Strafella³

2014

The Lancet

141

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Recent advances in structural and functional imaging have greatly improved our ability to assess normal functions of the basal ganglia, diagnose parkinsonian syndromes, understand the pathophysiology of parkinsonism and other movement disorders, and detect and monitor disease progression. Radionuclide imaging is the best way to detect and monitor dopamine deficiency, and will probably continue to be the best biomarker for assessment of the effects of disease-modifying therapies. However, advances in magnetic resonance enable the separation of patients with Parkinson's disease from healthy controls, and show great promise for differentiation between Parkinson's disease and other akinetic-rigid syndromes. Radionuclide imaging is useful to show the dopaminergic basis for both motor and behavioural complications of Parkinson's disease and its treatment, and alterations in non-dopaminergic systems. Both PET and MRI can be used to study patterns of functional connectivity in the brain, which is disrupted in Parkinson's disease and in association with its complications, and in other basal-ganglia disorders such as dystonia, in which an anatomical substrate is not otherwise apparent. Functional imaging is increasingly used to assess underlying pathological processes such as neuroinflammation and abnormal protein Correspondence to: Prof A J Stoessl,

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“…34,61 ACh is believed to be particularly important in regulating attention via projections from the basal forebrain nuclei to the DLPFC in animals 62 and humans. 63 The exact mechanism by which ACh modulates attention is unknown although it is established that ACh levels within the prefrontal cortex are transiently increased during tasks requiring attention.…”

Section: Acetylcholinementioning

confidence: 99%