Cholinergic changes in Lewy body disease: implications for presentation, progression and subtypes

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

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Cortical α4β2-nicotinic acetylcholine receptors and cognitive decline in Parkinson's disease

Journal of Parkinson s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

Background Autopsy and in vivo molecular imaging studies suggest altered binding of the α4β2-nicotinic cholinergic receptor (α4β2-nAChR) with cognitive dysfunction Parkinson's disease (PD). Objective To determine relationship between cortical hippocampal α4β2-nAChR [ 18 F]XTRA PET, a high-affinity radiotracer that enables quantification these regions, function individuals PD. Methods Individuals PD (N = 32) age-similar, controls without or dementia 10) completed assessment one 90-min, PET scan. Metabolite-corrected arterial input radioactivity time-activity curves were generated to obtain total distribution volume (V T ) across 12 regions interest (ROIs). was compared 1) people 2) controls, persons normal cognition (PD-NC), MCI (PD-MCI). Results higher occipital cortex combined group participants age-similar controls. No showed lower V with, but not without, partial correction different PD-NC, PD-MCI groups, this driven by Regression regional on domain T-scores, adjusting for age, worse performance visual-spatial memory tasks associated precuneus entire parietal cortex. Conclusions Higher posterior is found visual perception memory, possibly due occupancy endogenous acetylcholine.

Language: Английский

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Cholinergic degeneration and early cognitive signs in prodromal Lewy body dementia

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(2)

Published: Feb. 1, 2025

Abstract INTRODUCTION Isolated REM sleep behavior disorder (iRBD) is a strong prodromal marker of Lewy body diseases (LBDs) – Parkinson's disease (PD) and dementia with bodies (DLB). Cholinergic loss linked to cognitive decline in these conditions, but its trajectory remains unclear. METHODS In cohort 92 iRBD participants baseline MRI, cholinergic basal forebrain (cBF) volume was measured, longitudinal changes analyzed 49 follow‐up scans. Cross‐sectional neuropsychological associations were examined across broader RBD–LBD continuum, including the plus 65 PD 15 DLB patients probable RBD. RESULTS cBF declined at comparable rates iRBD‐to‐PD iRBD‐to‐DLB converters, atrophy more severe phenoconversion. correlated attention, executive, memory deficits. iRBD, z ‐score < −1.0 predicted (hazard ratio = 9.57, p .009). CONCLUSION degeneration evolves from stage LBDs predicts dementia, highlighting window for cholinergic‐targeted intervention. Highlights Basal links executive function, RBD continuum. progresses similar DLB. At phenoconversion, greater than converters. strongly future iRBD. Executive dysfunction faster

Language: Английский

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Illustrate the metabolic regulatory effects of Ganoderma Lucidum polysaccharides on cognitive dysfunction in formaldehyde-exposed mouse brain by mass spectrometry imaging

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 294, P. 118060 - 118060

Published: March 22, 2025

Language: Английский

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Multidimensional mechanisms of anxiety and depression in Parkinson’s Disease: integrating neuroimaging, neurocircuits, and molecular pathways

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107717 - 107717

Published: March 1, 2025

Anxiety and depression are common non-motor symptoms of Parkinson's disease (PD) that significantly affect patients' quality life. In recent years, our understanding PD has advanced through multifaceted studies on the pathological mechanisms associated with anxiety in PD. These classic psychiatric involve complex pathophysiology, both distinct features connections to underlying aetiology Furthermore, co-occurrence blurs boundaries between them. Therefore, a comprehensive summary pathogenic will aid better addressing emergence these This article integrates neuroanatomical, neural projection, neurotransmitter, neuroinflammatory, brain-gut axis, neurotrophic, hypothalamic-pituitary-adrenal genetic perspectives provide description core alterations PD, aiming an up-to-date perspective broader therapeutic prospects for patients suffering from or depression.

Language: Английский

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Cholinergic System Changes in Dopa‐Unresponsive Freezing of Gait in Parkinson's Disease

Movement Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Freezing of gait (FoG) is a debilitating mobility disturbance that becomes increasingly resistant to dopaminergic pharmacotherapies with advancing Parkinson's disease (PD). The pathophysiology underlying the response FoG treatment poorly understood. Prior vesicular acetylcholine transporter positron emission tomography (VAChT PET) imaging studies implicate degeneration cholinergic pathways, including bilateral striatal and limbic archicortex deficits, as significant contributors FoG. We aim investigate whether specific system changes are associated responsiveness levodopa in PD patients. Thirty six subjects (31M/5F) completed [18F]-fluoroethoxybenzovesamicol ([18F]FEOBV) underwent videotaped clinical assessments for on off levodopa. Sixteen had l-dopa-unresponsive Whole brain voxel-based analyses [18F]FEOBV PET (false discovery rate-corrected at P < 0.05 adjusted levodopa-equivalent dose) showed those more severe terminal deficits insula, hippocampi, fimbria, lateral geniculate nuclei; left mid-temporal, putamen, posterior cingulate regions; right mid-frontal region anterior ventral nucleus thalamus compared l-dopa-responsive unresponsive reductions, mostly extra-striatal regions involved multisensory cognitive integration postural control well spatial navigation. lack involvement points disruption widespread cerebral network functions may explain treatment-resistant nature © 2025 Author(s). Movement Disorders published by Wiley Periodicals LLC behalf International Parkinson Disorder Society.

Language: Английский

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Redefining Non-Motor Symptoms in Parkinson’s Disease

Journal of Personalized Medicine, Journal Year: 2025, Volume and Issue: 15(5), P. 172 - 172

Published: April 26, 2025

Parkinson’s disease involves widespread neurodegeneration that extends far beyond the basal ganglia, giving rise to a diverse range of non-motor symptoms frequently emerge before motor onset. These include autonomic dysfunction, cognitive decline, neuropsychiatric disturbances, sleep-related disorders, and sensory deficits. Here, we synthesize current evidence on anatomical, neurochemical, network-level mechanisms drive these symptoms, examine how they shape progression clinical heterogeneity. We highlight limitations dopamine-centric models advocate for framework treats as disorder’s primary, mechanistically distinct features. also discuss emerging technologies—such multi-omic profiling, artificial intelligence, network neuroscience—enable earlier identification, stratification phenotypes, development precision-based therapeutic strategies. Recognizing central redefines disorder should be diagnosed, studied, treated.

Language: Английский

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Cognitive impairment and vulnerability of cholinergic brain network in the Alzheimer’s continuum: free-water imaging based on diffusion tensor imaging

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: April 30, 2025

Increased extracellular free water (FW) is considered to provide better pathophysiological information than conventional diffusion tensor imaging (DTI) metrics. The cholinergic brain network a key hub for cognitive function, and microstructural changes detected by in this system may be associated with impairment Alzheimer's disease (AD). However, the specific impact of FW on domains across AD continuum their diagnostic value remain unclear. Here, we investigated basal forebrain alterations based water-corrected healthy controls (n = 36), amnestic mild (aMCI; n 31), group 33). subregions were divided into Broca diagonal band (Ch1-3) Meynert nucleus (Ch4). performance was measured using Montreal Cognitive Assessment (MoCA). Additionally, evaluated fraction (FWf) within system. FWf bilateral Ch1-3 Ch4 regions increased age, significantly higher aMCI (p < 0.001). In AD, correlated total MoCA score (R -0.42, p 0.015), especially visual spatial/executive -0.47, 0.006) orientation deficits -0.38, 0.029). No significant correlations found group. ROC curve analysis showed that had high efficacy versus HC (AUC 0.958, 95% CI 0.909-1.00), moderate 0.795, 0.685-0.905) 0.719, 0.589-0.850). captures damage entire continuum. These occur early but selectively affect domain-specific cognition later stages possibly through dysfunction. Our results highlight potential as biomarker decline.

Language: Английский

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PET/CT in Movement Disorders: Update

Seminars in Nuclear Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

This review synthesizes recent literature, primarily from the last 5 years, to highlight impact of innovative technologies and analytical approaches on application positron emission tomography (PET) in movement disorders. PET remains a cornerstone for investigating these conditions, with advancements enhancing our understanding disease pathophysiology progression. Established findings, such as ability [18F]-fluorodeoxyglucose (18F-FDG PET) differentiate Parkinson's (PD) atypical parkinsonian syndromes based characteristic metabolic patterns, have been consistently validated. PD typically presents relative hypermetabolism basal ganglia, thalamus cerebellum, while parkinsonisms exhibit more widespread subcortical hypometabolism. Technological innovations, particularly quantification methods connectivity analysis, improved diagnostic precision provided deeper insights into mechanisms. Dopaminergic imaging, crucial assessing presynaptic postsynaptic dysfunction, has also benefited advances. The field is further evolving development novel tracers targeting pathological hallmarks, alpha-synuclein multiple system atrophy (MSA), tau progressive supranuclear palsy (PSP) cortico-basal degeneration (CBD), neuroinflammation, microglial activation, neurotransmitter systems like serotonin acetylcholine. While not yet routinely used clinical assessment Huntington's or ataxia, research applications are expanding, driven by potential new techniques. These only reinforce existing knowledge but open avenues management

Language: Английский

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Impaired Respiratory Function as an Auxiliary Marker for Disease Progression in Different Motor Subtypes of Parkinson's Disease

Movement Disorders Clinical Practice, Journal Year: 2025, Volume and Issue: unknown

Published: May 6, 2025

Abstract Background The mechanisms underlying respiratory function impairments in different motor subtypes of Parkinson's disease (PD) remain poorly understood. Objectives This study aims to elucidate the differences between two main PD subtypes, tremor‐dominant (TD) and postural instability gait difficulty (PIGD), investigate their associations with severity. Methods A total 106 patients (59 TD 47 PIGD) 42 age‐ sex‐matched healthy controls (HCs) were enrolled. Pulmonary tests (PFTs), muscle strength, drive measurements conducted. Multivariate models employed analyze correlations indices clinical characteristics. Results Compared HCs, PIGD exhibited significant reductions forced vital capacity (FVC%) ( P = 0.018), peak expiratory flow (PEF%) < 0.001), diffusing for carbon monoxide adjusted hemoglobin (DLCOc%) 0.013), lung (TLC%) 0.045). Although not statistically significant, a more apparent declining trend was observed patients. Regarding showed severe maximal inspiratory pressure (PImax%) 0.001) (PEmax%) 0.001). linear regression analysis confirmed that PEF% determinant cognitive (β 0.497, whereas airway occlusion at 100 milliseconds (P0.1%) influenced levels −0.373, 0.015). Conclusions patients, have pronounced impairments. Specific correlate severity decline, highlighting potential as markers progression subtypes.

Language: Английский

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