Cholinergic system changes in Parkinson's disease: emerging therapeutic approaches

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

Published: Feb. 5, 2022

Language: Английский

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Emerging Neuroimaging Biomarkers Across Disease Stage in Parkinson Disease

JAMA Neurology, Journal Year: 2021, Volume and Issue: 78(10), P. 1262 - 1262

Published: Aug. 30, 2021

Imaging biomarkers in Parkinson disease (PD) are increasingly important for monitoring progression clinical trials and also have the potential to improve care management. This Review addresses a critical need make clear temporal relevance diagnostic imaging be used by clinicians researchers over course of PD. Magnetic resonance (diffusion imaging, neuromelanin-sensitive iron-sensitive T1-weighted imaging), positron emission tomography/single-photon computed tomography dopaminergic, serotonergic, cholinergic as well metabolic cerebral blood flow network neuroimaging preclinical, prodromal, early, moderate late stages characterized.

Language: Английский

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The Biology and Pathobiology of Glutamatergic, Cholinergic, and Dopaminergic Signaling in the Aging Brain

Frontiers in Aging Neuroscience, Journal Year: 2021, Volume and Issue: 13

Published: July 13, 2021

The elderly population is growing worldwide, with important health and socioeconomic implications. Clinical experimental studies on aging have uncovered numerous changes in the brain, such as decreased neurogenesis, increased synaptic defects, greater metabolic stress, enhanced inflammation. These are associated cognitive decline neurobehavioral deficits. Although not a disease, it significant risk factor for functional worsening, affective impairment, disease exaggeration, dementia, general susceptibility. Conversely, life events related to mental stress trauma can also lead accelerated age-associated disorders dementia. Here, we review human mice rats, those modeling neurodegenerative diseases, that helped elucidate (1) dynamics mechanisms underlying biological pathological of main projecting systems brain (glutamatergic, cholinergic, dopaminergic) (2) effect defective glutamatergic, dopaminergic projection disabilities disorders, Alzheimer’s Parkinson’s diseases. Detailed knowledge age-related diseases be an element development effective ways treatment. In this context, briefly analyze which adverse glutaminergic could targeted by therapeutic strategies developed result our better understanding these damaging mechanisms.

Language: Английский

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Depression in Patients with Parkinson’s Disease: Current Understanding of its Neurobiology and Implications for Treatment

Drugs & Aging, Journal Year: 2022, Volume and Issue: 39(6), P. 417 - 439

Published: June 1, 2022

Depression is one of the most frequent and burdensome non-motor symptoms in Parkinson's disease (PD), across all stages. Even when its severity mild, PD depression has a great impact on quality life for these patients their caregivers. Accordingly, accurate diagnosis, supported by validated scales, identification risk factors, recognition motor comorbid to are critical understanding neurobiology depression, which turn determines effectiveness dopaminergic drugs, antidepressants non-pharmacological interventions. Recent advances using vivo functional structural imaging demonstrate that underpinned dysfunction limbic networks monoaminergic systems, depending stage associated symptoms, including apathy, anxiety, rapid eye movement sleep behavior disorder (RBD), cognitive impairment dementia. In particular, evolution serotonergic, noradrenergic, abnormalities circuits time, involving anterior cingulate orbitofrontal cortices, amygdala, thalamus ventral striatum, help delineate variable expression with prodromal, early advanced PD. Evidence accumulating support use dual serotonin noradrenaline reuptake inhibitors (desipramine, nortriptyline, venlafaxine) moderate severe while selective inhibitors, repetitive transcranial magnetic stimulation behavioral therapy may also be considered. patients, recent findings advocate optimization dopamine replacement evaluation deep brain subthalamic nucleus improve represents an important first step, addition physical activity. Overall, this review indicates increasing neurobiological changes implement roadmap tailored interventions underlying subtypes prognosis.

Language: Английский

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The Cholinergic Brain in Parkinson's Disease

Movement Disorders Clinical Practice, Journal Year: 2021, Volume and Issue: 8(7), P. 1012 - 1026

Published: Aug. 2, 2021

The central cholinergic system includes the basal forebrain nuclei, mainly projecting to cortex, mesopontine tegmental thalamus and subcortical structures, other groups of neurons interneurons. This regulates many functions human behavior such as cognition, locomotion, sleep. In Parkinson's disease (PD), disruption transmission has been associated with cognitive decline, gait problems, freezing (FOG), falls, REM sleep disorder (RBD), neuropsychiatric manifestations, olfactory dysfunction. Neuropathological neuroimaging evidence suggests that pathology occurs simultaneously nigrostriatal denervation, whereas in pontine nuclei may occur before onset motor symptoms. These studies have also detailed clinical implications dysfunction PD. Degeneration consequential cortical denervation are predict subsequent development decline Gait FOG, falls a complex both nuclei. Olfactory impairment is limbic archicortex, specifically hippocampus amygdala. Available dysfunction, alongside failure dopaminergic neurotransmitters systems, contributes generation specific set manifestations. Therefore, "cholinergic phenotype" can be identified people presenting RBD. this review, we will summarize organization correlates

Language: Английский

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Changing views of the pathophysiology of Parkinsonism

Movement Disorders, Journal Year: 2019, Volume and Issue: 34(8), P. 1130 - 1143

Published: June 19, 2019

ABSTRACT Studies of the pathophysiology parkinsonism (specifically akinesia and bradykinesia) have a long history primarily model consequences dopamine loss in basal ganglia on function ganglia/thalamocortical circuit(s). Changes firing rates individual nodes within these circuits were originally considered central to parkinsonism. However, this view has now given way belief that changes patterns related nuclei are more important, including emergence burst discharges, greater synchrony between neighboring neurons, oscillatory activity patterns, excessive coupling activities at different frequencies. Primarily focusing studies obtained nonhuman primates human patients with Parkinson's disease, review summarizes current state field highlights several emerging areas research, impact heterogeneity external pallidal neurons parkinsonism, importance extrastriatal loss, parkinsonism‐associated synaptic morphologic plasticity, potential role(s) cerebellum brainstem motor dysfunction disease. © 2019 International Parkinson Movement Disorder Society

Language: Английский

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Neuroimaging advances in Parkinson's disease with freezing of gait: A systematic review

NeuroImage Clinical, Journal Year: 2019, Volume and Issue: 24, P. 102059 - 102059

Published: Jan. 1, 2019

Freezing of gait (FOG) is a paroxysmal disorder that often occurs at advanced stages Parkinson's disease (PD). FOG consists abrupt walking interruption and severe difficulty in locomotion with an increased risk falling. Pathophysiological mechanisms underpinning PD are still unclear. However, MRI nuclear medicine studies have gained relevant insights into the pathophysiology PD. Neuroimaging demonstrated structural functional abnormalities number cortical subcortical brain regions patients FOG. In this paper, we systematically review existing neuroimaging literature on changes described FOG, according to Preferred Reporting Items for Systematic Reviews Meta-Analyses guidelines. We evaluate previous using various techniques estimate grey matter loss white degeneration. Moreover, by examining imaging studies. The current provides up-to-date knowledge field summarizes possible responsible

Language: Английский

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Altered Cholinergic Innervation in De Novo Parkinson's Disease with and Without Cognitive Impairment

Movement Disorders, Journal Year: 2022, Volume and Issue: 37(4), P. 713 - 723

Published: Jan. 17, 2022

Abstract Background Altered cholinergic innervation plays a putative role in cognitive impairment Parkinson's disease (PD) at least advanced stages. Identification of the relationship between and early will provide better insight into prognosis possible intervention. Objective The aim was to assess regional status de novo patients with PD, without impairment. Methods Fifty‐seven newly diagnosed, treatment‐naive, PD (32 men, mean age 64.6 ± 8.2 years) 10 healthy controls (5 54.6 6.0 were included. All participants underwent [ 18 F]fluoroethoxybenzovesamicol positron emission tomography detailed neuropsychological assessment. classified as either cognitively normal (PD‐NC) or mild (PD‐MCI). Whole brain voxel‐based group comparisons performed. Results show bidirectional changes PD. Both PD‐NC PD‐MCI groups showed significant cortical denervation compared ( P < 0.05, false discovery rate corrected), primarily posterior regions. Higher‐than‐normal binding most prominent both subcortical regions, including cerebellum, cingulate cortex, putamen, gyrus rectus, hippocampus, amygdala. Conclusion is already present Posterior losses all independent status. cerebellar, frontal, regions intact may reflect compensatory upregulation early‐stage Limited failing play an important early, clinically evident © 2022 Authors. Movement Disorders published by Wiley Periodicals LLC on behalf International Parkinson Disorder Society

Language: Английский

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Cognition and freezing of gait in Parkinson's disease: A systematic review and meta-analysis

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 147, P. 105068 - 105068

Published: Feb. 2, 2023

Language: Английский

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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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