Cholinergic basal forebrain atrophy in Parkinson's disease with freezing of gait DOI Creative Commons

Caiting Gan,

Xingyue Cao,

Lina Wang

et al.

Annals of Clinical and Translational Neurology, Journal Year: 2023, Volume and Issue: 10(5), P. 814 - 824

Published: March 31, 2023

Abstract Background Mounting research support that cholinergic dysfunction plays a prominent role in freezing of gait (FOG), which commonly occurs Parkinson's disease (PD). Basal forebrain (BF), especially the nuclei 4 (Ch4), provides primary source brain input. However, whether degeneration BF and its innervated cortex contribute to pathogenesis FOG is unknown. Objective To explore structural alterations cortical regions PD patients with freezing. Methods Magnetic resonance imaging assessments neurological were performed on 20 (PD‐FOG), without (PD‐NFOG), 21 healthy participants. Subregion volumes compared among groups. Local gyrification index (LGI) was computed reveal alternations. Relationships subregional volumes, LGI, severity evaluated by multiple linear regression. Results Our study discovered that, PD‐NFOG, PD‐FOG exhibited significant Ch4 atrophy ( p = 4.6 × 10 −5 ), accompanied decreased LGI values left entorhinal 3.00 ) parahippocampal gyrus 2.90 ). Based regression analysis, volume negatively associated group β −12.224, T −2.556, 0.031). Interpretation results imply microstructural disorganization may play important roles PD‐FOG.

Language: Английский

Cholinergic system changes in Parkinson's disease: emerging therapeutic approaches DOI
Nicolaas I. Bohnen, Alison J. Yarnall, Rimona S. Weil

et al.

The Lancet Neurology, Journal Year: 2022, Volume and Issue: 21(4), P. 381 - 392

Published: Feb. 5, 2022

Language: Английский

Citations

185
Pharmacological Treatment of Tremor in Parkinson’s Disease Revisited DOI Creative Commons
Walter Pirker, Regina Katzenschlager, Mark Hallett

et al.

Journal of Parkinson s Disease, Journal Year: 2023, Volume and Issue: 13(2), P. 127 - 144

Published: Feb. 24, 2023

The pathophysiology of Parkinson’s disease (PD) tremor remains incompletely understood and there is a lack clinical trials specifically addressing its pharmacological treatment. Levodopa the most efficacious drug for patients should be used as primary approach to control troublesome tremor. While efficacy oral dopamine agonists on PD has been demonstrated in controlled trials, no evidence greater antitremor compared levodopa. magnitude effect anticholinergics generally lower than that Due their adverse effects, have limited role selected young cognitively intact patients. Propranolol may improve resting action considered an adjunct with insufficient response levodopa this also applies clozapine, despite unfavorable profile. Treating motor fluctuations MAO-B COMT inhibitors, agonists, amantadine, or on-demand treatments such subcutaneous sublingual apomorphine inhaled well continuous infusions will off period episodes. For drug-refractory optimization deep brain stimulation focused ultrasound are first-line considerations. Surgery can highly effective treatment medication-refractory without fluctuations. present review highlights essentials parkinsonian tremor, critically examines available trial data effects medication surgical approaches provides guidance choice practice.

Language: Английский

Citations

43
Severe cholinergic terminal loss in newly diagnosed dementia with Lewy bodies DOI Open Access
Niels Okkels, Jacob Horsager, Miguel A. Labrador‐Espinosa

et al.

Brain, Journal Year: 2023, Volume and Issue: 146(9), P. 3690 - 3704

Published: June 3, 2023

Cholinergic changes play a fundamental role in the natural history of dementia with Lewy bodies and body disease general. Despite important achievements field cholinergic research, significant challenges remain. We conducted study four main objectives: (i) to examine integrity terminals newly diagnosed bodies; (ii) disentangle contribution by comparing patients without dementia; (iii) investigate vivo relationship between terminal loss atrophy cell clusters basal forebrain at different stages disease; (iv) test whether any asymmetrical degeneration would correlate motor dysfunction hypometabolism. To achieve these objectives, we comparative cross-sectional 25 (age 74 ± 5 years, 84% male), 15 healthy control subjects 75 6 67% male) Parkinson's 70 7 60% male). All participants underwent 18F-fluoroetoxybenzovesamicol PET high-resolution structural MRI. In addition, collected clinical 18F-fluorodeoxyglucose images. Brain images were normalized standard space regional tracer uptake volumetric indices extracted. Patients showed spatially distinct reductions across cerebral cortex, limbic system, thalamus brainstem. Also, binding cortical regions correlated quantitatively forebrain. contrast, decreased cortex despite preserved volumes. dementia, most severe least occipital compared those dementia. Interhemispheric asymmetry brain metabolism lateralized function. conclusion, this provides robust evidence for bodies, which correlates imaging measures degeneration. our findings suggest that function occurs 'before' neuronal Moreover, supports system is may be linked other transmitter systems. Our have implications understanding how pathology contributes features disease, progression patterns.

Language: Английский

Citations

26
Cholinergic changes in Lewy body disease: implications for presentation, progression and subtypes DOI
Niels Okkels, Michel J. Grothe, John‐Paul Taylor

et al.

Brain, Journal Year: 2024, Volume and Issue: 147(7), P. 2308 - 2324

Published: Feb. 29, 2024

Cholinergic degeneration is significant in Lewy body disease, including Parkinson's dementia with bodies, and isolated REM sleep behaviour disorder. Extensive research has demonstrated cholinergic alterations the CNS of these disorders. More recently, studies have revealed denervation organs that receive parasympathetic denervation. This enables a comprehensive review changes encompassing both central peripheral regions, various disease stages diagnostic categories. Across studies, brain regions affected show equal or greater levels impairment compared to without dementia. observation suggests continuum between Patients exhibit relative sparing limbic whereas occipital superior temporal appear be similar extent patients implies posterior cell groups basal forebrain are early disorders, while more anterior typically later progression. The topographical observed by comorbid Alzheimer pathology may reflect combination seen pure forms those Alzheimer's disease. co-pathology important understand Thalamic innervation dementia, this contribute distinct clinical presentations groups. In thalamus variably affected, suggesting different sequential involvement disorder demonstrate abdominal from dorsal motor nucleus vagus, who experienced their prodrome. for understanding prodromal manifest phases conclusion, carry implications phenotypes influence co-pathology, delineating subtypes pathological spreading routes, developing tailored treatments targeting system.

Language: Английский

Citations

15
Cholinergic systems, attentional-motor integration, and cognitive control in Parkinson's disease DOI
Roger L. Albin, Sygrid van der Zee, Teus van Laar

et al.

Progress in brain research, Journal Year: 2022, Volume and Issue: unknown, P. 345 - 371

Published: Jan. 1, 2022

Language: Английский

Citations

34
Cerebral topography of vesicular cholinergic transporter changes in neurologically intact adults: A [18F]FEOBV PET study DOI Creative Commons
Prabesh Kanel, Sygrid van der Zee, Carlos A. Sánchez-Catasús

et al.

Aging Brain, Journal Year: 2022, Volume and Issue: 2, P. 100039 - 100039

Published: Jan. 1, 2022

Acetylcholine plays a major role in brain cognitive and motor functions with regional cholinergic terminal loss common several neurodegenerative disorders. We describe age-related declines of neuron density vivo using the positron emission tomography (PET) ligand [18F](-)5-Fluoroethoxybenzovesamicol ([18F] FEOBV), vesamicol analogue selectively binding to vesicular acetylcholine transporter (VAChT). A total 42 subjects without clinical evidence neurologic disease (mean 50.55 [range 20-80] years, 24 Male/18 Female) underwent [18F]FEOBV PET imaging. used SPM based voxel-wise statistical analysis perform whole voxel-based parametric (family-wise error corrected, FWE) also extract most significant clusters regions correlating aging gender as nuisance variable. Age-related VAChT reductions were found primary sensorimotor cortex, visual caudate nucleus, anterior mid-cingulum, bilateral insula, para-hippocampus, hippocampus, temporal lobes/amygdala, dorsomedial thalamus, metathalamus, cerebellum (gender FWE-corrected, P < 0.05). These findings show specific topographic pattern vulnerability nerve terminals across multiple systems accompanying aging.

Language: Английский

Citations

29
Atrophy of the Cholinergic Basal Forebrain can Detect Presynaptic Cholinergic Loss in Parkinson's Disease DOI Creative Commons
Nicola Ray, Prabesh Kanel, Nicolaas I. Bohnen

et al.

Annals of Neurology, Journal Year: 2023, Volume and Issue: 93(5), P. 991 - 998

Published: Jan. 4, 2023

Structural imaging of the cholinergic basal forebrain may provide a biomarker for system integrity that can be used in motor and non-motor outcome studies Parkinson's disease. However, no prior have validated these structural metrics with nerve terminal vivo Here, we correlate morphometry topography vesicular acetylcholine transporter large sample.

Language: Английский

Citations

18
Mapping Cholinergic Synaptic Loss in Parkinson’s Disease: An [18F]FEOBV PET Case-Control Study DOI
Jacob Horsager, Niels Okkels, Allan K. Hansen

et al.

Journal of Parkinson s Disease, Journal Year: 2022, Volume and Issue: 12(8), P. 2493 - 2506

Published: Nov. 1, 2022

Cholinergic degeneration is strongly associated with cognitive decline in patients Parkinson's disease (PD) but may also cause motor symptoms and olfactory dysfunction. Regional differences are striking reflect different PD related progression patterns.To map quantify the regional cerebral cholinergic alterations non-demented patients.We included 15 early-moderate stage age- sex-matched healthy controls for [18F]FEOBV positron emission tomography imaging. We quantitated variations using VOI-based analyses which were supported by a vertex-wise cluster analysis. Correlations between imaging data clinical neuropsychological explored.We found significantly decreased uptake global neocortex (38%, p = 0.0002). The most severe reductions seen occipital posterior temporo-parietal regions (p < 0.0001). analysis corroborated these findings. All subcortical structures showed modest non-significant reductions. Motor (postural instability gait difficulty) cognition (executive function composite z-score) correlated (thalamus cingulate cortex/insula/hippocampus, respectively), correlations not statistically significant after multiple comparison correction. A strong correlation was interhemispheric asymmetry, symptom asymmetry of extremities (r 0.84, 0.0001).Cortical prominent patients, more subtle structures. suggest uneven involvement nuclei brain represent window to follow progression. asymmetric neocortical indicates that unilateral parallels ipsilateral dopaminergic degeneration.

Language: Английский

Citations

25
Recent developments in the understanding of the interactions between the vestibular system, memory, the hippocampus, and the striatum DOI Creative Commons
Paul F. Smith

Frontiers in Neurology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 2, 2022

Over the last two decades, evidence has accumulated to demonstrate that vestibular system extensive connections with areas of brain related spatial memory, such as hippocampus, and also it significant interactions associated voluntary motor control, striatum in basal ganglia. In fact, these functions are far from separate is believed between hippocampus important for memory processing. The data relating vestibular-hippocampal-striatal have considerable implications understanding treatment Alzheimer's Disease Parkinson's Disease, addition other neurological disorders. However, accumulating rapidly, difficult keep up latest developments areas. aim this review summarize critically evaluate relevant been published over 2 years (i.e., since 2021), order identify emerging themes research area.

Language: Английский

Citations

23
Discussion of Research Priorities for Gait Disorders in Parkinson's Disease DOI
Nicolaas I. Bohnen, Rui M. Costa, William T. Dauer

et al.

Movement Disorders, Journal Year: 2021, Volume and Issue: 37(2), P. 253 - 263

Published: Dec. 22, 2021

ABSTRACT Gait and balance abnormalities develop commonly in Parkinson's disease are among the motor symptoms most disabling refractory to dopaminergic or other treatments, including deep brain stimulation. Efforts effective therapies challenged by limited understanding of these complex disorders. There is a major need for novel appropriately targeted research expedite progress this area. The Scientific Issues Committee International Parkinson Movement Disorder Society has charged panel experts field consider current knowledge gaps determine routes with highest potential generate groundbreaking data. © 2021

Language: Английский

Citations

32