The microbiome–gut–brain axis in Parkinson disease — from basic research to the clinic

Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 18(8), P. 476 - 495

Published: June 24, 2022

Language: Английский

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TLR2 and TLR4 in Parkinson’s disease pathogenesis: the environment takes a toll on the gut

Translational Neurodegeneration, Journal Year: 2021, Volume and Issue: 10(1)

Published: Nov. 17, 2021

Abstract Parkinson’s disease (PD) is an incurable, devastating disorder that characterized by pathological protein aggregation and neurodegeneration in the substantia nigra. In recent years, growing evidence has implicated gut environment gut-brain axis pathogenesis progression of PD, especially a subset people who exhibit prodromal gastrointestinal dysfunction. Specifically, perturbations homeostasis are hypothesized to contribute α-synuclein enteric neurons, which may spread brain over decades eventually result characteristic central nervous system manifestations including motor impairments. However, mechanisms linking disturbances still unclear. A plethora research indicates toll-like receptors (TLRs), TLR2 TLR4, critical mediators homeostasis. Alongside their established role innate immunity throughout body, studies increasingly demonstrating TLR4 signalling shapes development function system. Notably, dysregulated patients with thus be early dysfunction PD. To better understand putative contribution intestinal we critically discuss normal as well for altered reviewing clinical, animal model vitro research. Growing on immunological aetiology also discussed, focus interactions TLR4. We propose conceptual PD microbial dysbiosis alters permeability barrier signalling, ultimately leading positive feedback loop chronic promoting vagal neurons. turn, aggregates then migrate via peripheral nerves, such nerve, neuroinflammation typically associated

Language: Английский

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Prevalence of Prodromal Symptoms of Parkinson’s Disease in the Late Middle-Aged Population

Journal of Parkinson s Disease, Journal Year: 2022, Volume and Issue: 12(3), P. 967 - 974

Published: Feb. 18, 2022

The prodromal phase of Parkinson's disease (PD) can last up to 20 years and is characterized by a variety non-motor symptoms.

Language: Английский

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Comorbid neurotrauma increases neurodegenerative-relevant cognitive, motor, and autonomic dysfunction in patients with rapid eye movement sleep behavior disorder: a substudy of the North American Prodromal Synucleinopathy Consortium

SLEEP, Journal Year: 2024, Volume and Issue: 47(6)

Published: Jan. 5, 2024

Abstract Study Objectives Rapid eye movement sleep behavior disorder (RBD) is strongly associated with phenoconversion to an overt synucleinopathy, e.g. Parkinson’s disease (PD), Lewy body dementia, and related disorders. Comorbid traumatic brain injury (TBI) posttraumatic stress (PTSD)—henceforth “neurotrauma” (NT)—increase the odds of RBD by ~2.5-fold are increased rate service-connected PD in Veterans. Thus, NT both independently PD; however, it unclear how influences neurological function patients RBD. Methods Participants ≥18 years overnight polysomnogram-confirmed were enrolled between 8/2018 4/2021 through North American Prodromal Synucleinopathy Consortium. Standardized assessments for RBD, TBI, PTSD history, as well cognitive, motor, sensory, autonomic function, completed. This cross-sectional analysis compared cases (n = 24; + NT) controls 96; RBD), matched age (~60 years), sex (15% female), education (~15 years). Results reported earlier symptom onset (37.5 ± 11.9 vs. 52.2 15.1 age) a more severe phenotype. Similarly, anxiety depression, greater frequency hypertension, significantly worse No differences olfaction or color vision observed. Conclusions cross-sectional, case:control study shows individuals have measures common features synucleinopathy. Confirmatory longitudinal studies ongoing; these results suggest may be advanced symptoms evolving neurodegenerative process.

Language: Английский

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Constipation in Parkinson’s Disease: A Systematic Review and Meta-Analysis

European Neurology, Journal Year: 2022, Volume and Issue: 86(1), P. 34 - 44

Published: Dec. 5, 2022

Introduction: Constipation is a common nonmotor symptom of Parkinson’s disease (PD) and has been reported to increase the risk developing PD. However, previous studies have yielded conflicting results. Understanding this correlation may promote early diagnosis treatment PD, which could help patients improve their quality life. This study aimed investigate association between constipation PD onset. Methods: The was conducted in accordance with Preferred Reporting Items for Systematic Reviews Meta-Analyses (PRISMA) Meta-analyses Observational Studies Epidemiology (MOOSE) guidelines. We searched Medline, Embase, Scopus, SINOMED, Cochrane databases as well specific journals from inception September 2021 observational that evaluated Newcastle-Ottawa Scale used evaluate methodological included studies. Associations were summarized odds ratios (ORs) using random-effects model. Subgroup, meta-regression, sensitivity analyses performed. Results: Seventeen comprising 3,024,193 participants (case-control = 1,636,831; cohort 1,387,362) eligible inclusion. pooled OR 2.36 (95% confidence interval: 1.93–2.88), although strong heterogeneity observed (I2 90%, p < 0.01). Subgroup meta-regression indicated design duration major sources heterogeneity. A analysis confirmed stability outcomes. In addition, prevalence among those prodromal 20%, whereas it only 11% control group (p Moreover, there no significant age-based differences stage controls > 0.05). Conclusion: relatively high incidence phase associated an increased

Language: Английский

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Gastrointestinal Dysfunction in Parkinson’s Disease: Neuro-Gastroenterology Perspectives on a Multifaceted Problem

Journal of Movement Disorders, Journal Year: 2023, Volume and Issue: 16(2), P. 138 - 151

Published: May 24, 2023

Patients with Parkinson’s disease (PD) face a multitude of gastrointestinal (GI) symptoms, including nausea, bloating, reduced bowel movements, and difficulties defecation. These symptoms are common may accumulate during the course PD but often under-recognized challenging to manage. Objective testing can be burdensome patients does not correlate well symptoms. Effective treatment options limited. Evidence is based on studies in general population, specific evidence scarce. Upper GI dysfunction also interfere pharmacological motor which poses significant management challenges. Several new less invasive assessment tools novel have emerged recent years. The current review provides an overview practical approach recognizing diagnosing upper lower problems PD, e.g., dyspepsia, gastroparesis, small dysfunction, chronic constipation, defecatory dysfunction. Management aspects discussed latest from populations, insights for future research pertaining PD.

Language: Английский

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The role of the microbiota-gut-brain axis and intestinal microbiome dysregulation in Parkinson’s disease

Frontiers in Neurology, Journal Year: 2023, Volume and Issue: 14

Published: May 25, 2023

Parkinson’s disease (PD) is a complex progressive neurodegenerative associated with aging. Its main pathological feature the degeneration and loss of dopaminergic neurons related to misfolding aggregation α-synuclein. The pathogenesis PD has not yet been fully elucidated, its occurrence development process are closely microbiota-gut-brain axis. Dysregulation intestinal microbiota may promote damage epithelial barrier, inflammation, upward diffusion phosphorylated α-synuclein from enteric nervous system (ENS) brain in susceptible individuals further lead gastrointestinal dysfunction, neuroinflammation, neurodegeneration central (CNS) through disordered present review aimed summarize recent advancements studies focusing on role axis PD, especially mechanism microbiome dysregulation, dysfunction PD. Maintaining or restoring homeostasis gut microenvironment by targeting provide future direction for new biomarkers early diagnosis therapeutic strategies slow progression.

Language: Английский

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Lifelong Association of Disorders Related to Military Trauma with Subsequent Parkinson's Disease

Movement Disorders, Journal Year: 2023, Volume and Issue: 38(8), P. 1483 - 1492

Published: June 13, 2023

ABSTRACT Background Trauma‐related disorders such as traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are emerging risk factors for Parkinson's disease (PD), but their association with development of PD independence from comorbid remains unknown. Objective To examine TBI PTSD related to early trauma in military veterans using a case‐control study. Methods was identified by International Classification Diseases (ICD) code, recurrent PD‐specific prescriptions, availability 5+ years earlier records. Validation performed chart review movement disorder–trained neurologist. Control subjects were matched 4:1 age, duration preceding health care, race, ethnicity, birth year, sex. ICD code onset based on active duty. Association interaction measured going back 60 years. Interaction disorders. Results A total 71,933 cases 287,732 controls identified. increased odds subsequent at all 5‐year intervals year −60 (odds ratio range: 1.5 [1.4, 1.7] 2.1 [2.0, 2.1]). showed synergism (synergy index 1.14 [1.09, 1.29] 1.28 1.51]) additive 2.2 [1.6, 2.8] 2.7 [2.5, 2.8]). Chronic pain migraine greatest synergy TBI. Effect sizes trauma‐related comparable established prodromal Conclusions associated later synergistic chronic migraine. These findings provide evidence decades could aid prognostic calculation intervention. © 2023 Parkinson Movement Disorder Society. This article has been contributed U.S. Government employees work is the public domain USA.

Language: Английский

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Prodromal Parkinson’s Disease

Neurologic Clinics, Journal Year: 2025, Volume and Issue: 43(2), P. 209 - 228

Published: Jan. 22, 2025

Language: Английский

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Heart rate variability impairment during sleep in Veterans with rapid eye movement sleep behaviour disorder, traumatic brain injury, and post‐traumatic stress disorder: an early potential window into autonomic dysfunction?

Journal of Sleep Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Individuals with comorbid rapid eye movement (REM) sleep behaviour disorder (RBD) and neurotrauma (NT; defined by traumatic brain injury post-traumatic stress disorder) have an earlier age of RBD symptom onset, increased RBD-related severity more neurological features indicative prodromal synucleinopathy compared to only. An early sign neurodegenerative condition is autonomic dysfunction, which we sought evaluate examining heart rate variability during sleep. Participants overnight polysomnography were recruited from the Veterans Affairs Portland Health Care System. without NT or (controls, n = 19), only (RBD, 14), (RBD+NT, 19) evaluated. Eligible 5-min non-REM (NREM) REM epochs apneas/hypopneas, microarousals, ectopic beats analysed for frequency time domain (e.g., low-frequency [LF] power; high-frequency [HF] root mean square successive R-R intervals [RMSSD]; percentage that vary ≥50 ms [pNN50]) outcomes. Heart did not significantly differ between groups in any stage. Time variables LF power, HF RMSSD, pNN50) reduced RBD+NT group controls RBD-only NREM There no differences detected These data suggest significant reductions participants, suggesting greater dysfunction alone. may be early, promising biomarker, yielding mechanistic insight diagnosis prognosis neurodegeneration this vulnerable population.

Language: Английский

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