Olfactory impairment as an early marker of Parkinson’s disease in REM sleep behaviour disorder: a systematic review and meta-analysis

Olfactory impairment and rapid eye movement sleep behaviour disorder (RBD) are prodromal symptoms of Parkinson’s disease (PD) that may be associated with each other. This review aims to investigate the significance of olfaction in the diagnosis and prognosis of patients with RBD and to assess moderating factors affecting olfactory performance. We searched articles on olfaction in RBD and PD in five electronic databases. We identified 32 studies for the systematic review and used 28 of those, including 2858 participants for meta-analysis. Results revealed significant deficits in odour identification (g=−1.80; 95% CI: −2.17 to −1.43), threshold (g=−1.29; 95% CI: −1.67 to −0.91), discrimination (g=−1.08; 95% CI: −1.28 to −0.87) and overall olfactory function (g=−1.64; 95% CI: −1.94 to −1.35) in patients with RBD. Except for the Unified Parkinson's Disease Rating Scale Part III scores, none of the known moderating variables (including age, sex, disease duration and years of education) accounted for the olfactory function heterogeneity in patients with RBD. We identified similar olfactory impairments in patients with RBD and patients with PD (either with or without underlying RBD). These findings suggest that olfactory impairment may be a sensitive and stable diagnostic biomarker of RBD and appears to be useful for identifying patients with idiopathic RBD at high risk for early conversion to PD.

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Efficacy and safety of treatments for REM sleep behaviour disorder in Parkinson’s disease: a systematic review and Bayesian network meta-analysis protocol

BMJ Open ◽

10.1136/bmjopen-2020-047934 ◽

2021 ◽

Vol 11 (12) ◽

pp. e047934

Author(s):

Fabin Lin ◽

Yanhong Weng ◽

Xiaofeng Lin ◽

Dihang Wu ◽

Yixiao Su ◽

...

Keyword(s):

Systematic Review ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Meta Analysis ◽

Cochrane Collaboration ◽

Case Control ◽

Cochrane Library ◽

Behaviour Disorder ◽

Sleep Behaviour ◽

The Cochrane Collaboration

IntroductionSleep disorders are the main non-motor characteristics of Parkinson’s disease (PD). The quality of life is significantly impacted by rapid eye movement sleep behaviour disorder (RBD). It is not clearly evidenced in the literature that some medications can reduce the dream activities of patients with PD and RBD and improve sleep quality. And, they have side effects that may increase the severity of this disease. To further understand which medication has better efficacy and fewer adverse effects for patients with PD and RBD, it is necessary to perform a network meta-analysis.Methods and analysisThis protocol is performed accordingly to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols and the Cochrane Collaboration Handbook.A thorough literature selection will be conducted up to September 2021 using PubMed, Cochrane Library (The Cochrane Database of Systematic Reviews) and Embase. We will not only include randomised controlled trials, but prospective, retrospective cohort, case–control, nested case–control, case–cohort, cross-sectional and case series. We will use the Cochrane Collaboration tool to assess the risk of bias. Pairwise and network meta-analyses will be conducted using the R netmeta package and Stata V.14.0. The relative ranking probability of the best intervention will be estimated using the surface under the cumulative ranking curve. Additionally, sensitivity analysis, subgroup analysis, quality assessment and publication bias analysis will be performed.Ethics and disseminationNo research ethics approval is required for this systematic review, as no confidential patient data will be used. We will disseminate our findings through publication in a peer-reviewed journal and conference presentations, and our review will support development of a BMJ Rapid Recommendations providing contextualised clinical guidance based on this body of evidence.PROSPERO registration numberCRD42020206958.

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Effects of bilateral stimulation of the subthalamic nucleus in Parkinson's disease with and without REM sleep behaviour disorder

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2019-320858 ◽

2019 ◽

pp. jnnp-2019-320858 ◽

Cited By ~ 1

Author(s):

Panagiotis Bargiotas ◽

Ines Debove ◽

Ioannis Bargiotas ◽

Martin Lenard Lachenmayer ◽

Maria Ntafouli ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Depression Score ◽

Behaviour Disorder ◽

Group 14 ◽

Nucleus Subthalamicus ◽

Sleep Behaviour ◽

Disease Rating ◽

Clinical Profiles

BackgroundAlthough rapid eye movement sleep behaviour disorder (RBD) in Parkinson’s disease (PD) is associated with increased non-motor symptoms, its impact on the deep brain stimulation (DBS) outcome remains unclear. This is the first study to compare the post-DBS outcome between PD patients with RBD (PD-RBD+) and without (PD-RBD-).MethodsWe analysed data from PD patients who were treated with bilateral DBS in the nucleus subthalamicus. Assessments included night-polysomnography (only pre-DBS), and motor and non-motor assessments pre-DBS and post-DBS.ResultsAmong 50 PD patients (29 males, mean age 62.5 years, 11.8 mean PD years), 24 (48%) had RBD. Pre-DBS, the two groups were equal in respect to sociodemographic features, disease duration and PD medications. A multivariate analysis showed that the clinical profile linked to motor, non-motor and quality of life features differed significantly between PD patients with and without RBD. The most discriminative elements were Unified Parkinson’s Disease Rating Scale (UPDRS)-III, apathy and depression scores. Post-DBS, UPDRS-III, Epworth sleepiness scale and PD questionnaire improved significantly in both groups. UPDRS-II scores significantly improved in the PD-RBD+ group (−45%) but remained unchanged in the PD-RBD- group (−14%). The depression score improved significantly in the PD-RBD+ (−34%) and remained unchanged in the PD-RBD- group. The apathy score remained unchanged in the PD-RBD+ group but increased significantly in the PD-RBD- group (+33%).ConclusionWhile pre-DBS, PD patients with and without RBD showed different clinical profiles, post-DBS, the clinical profiles were comparable between the two groups. In respect to depressive symptoms, apathy and activities of daily living, PD-RBD+ patients show favourable post-DBS outcome. These findings highlight the importance of RBD assessment prior to DBS surgery.

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Evolution of prodromal Parkinson’s disease and dementia with Lewy bodies: a prospective study

Brain ◽

10.1093/brain/awz111 ◽

2019 ◽

Vol 142 (7) ◽

pp. 2051-2067 ◽

Cited By ~ 35

Author(s):

Seyed-Mohammad Fereshtehnejad ◽

Chun Yao ◽

Amelie Pelletier ◽

Jacques Y Montplaisir ◽

Jean-François Gagnon ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rem Sleep ◽

Colour Vision ◽

Rating Scale ◽

Lewy Bodies ◽

Behaviour Disorder ◽

Mixed Effect ◽

Sleep Behaviour ◽

Rem Sleep Behaviour Disorder

Abstract Parkinson’s disease has a long prodromal stage with various subclinical motor and non-motor manifestations; however, their evolution in the years before Parkinson’s disease is diagnosed is unclear. We traced the evolution of early motor and non-motor manifestations of synucleinopathy from the stage of idiopathic rapid eye movement (REM) sleep behaviour disorder until defined neurodegenerative disease. During 2004–16, we recruited and then annually followed 154 polysomnography-proven patients with idiopathic REM sleep behaviour disorder, of whom 55 phenoconverted to defined parkinsonism or dementia. Longitudinal data on multiple prodromal features, including the Unified Parkinson’s Disease Rating Scale parts I–III, quantitative motor tests, olfaction, colour vision, cognition, and autonomic functions were gathered annually (average = five follow-up visits, range: 2–12 years). The same measures were also assessed in 102 age- and sex-matched healthy control subjects. By looking backward from the time of dementia or parkinsonism diagnosis, we examined trajectories of each prodromal feature using mixed effect models. Based on analysis, olfactory loss was first to develop, with predicted onset >20 years before phenoconversion. This was followed by impaired colour vision, constipation, and erectile dysfunction, starting 10–16 years prior to phenoconversion. At 7–9 years before phenoconversion, slight urinary dysfunction and subtle cognitive decline could be detected. Among motor symptoms altered handwriting, turning in bed, walking, salivation, speech, and facial expression began to be disrupted starting 7–11 years prior to parkinsonism diagnosis, but remained mild until soon before phenoconversion. Motor examination abnormalities began 5–7 years before phenoconversion, with the alternate tap test having the longest interval (8 years before phenoconversion). Among cardinal motor phenotypes, bradykinesia appeared first, ∼5–6 years prior to phenoconversion, followed by rigidity (Year −3) and tremor (Year −2). With direct prospective evaluation of an idiopathic REM sleep behaviour disorder cohort during phenoconversion, we documented an evolution of prodromal manifestations similar to that predicted by pathological staging models, with predicted prodromal intervals as long as 20 years.

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Acupuncture-Related Therapies for Parkinson's Disease: A Meta-Analysis and Qualitative Review

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.676827 ◽

2021 ◽

Vol 13 ◽

Author(s):

Xiaopeng Wen ◽

Kunbin Li ◽

Hao Wen ◽

Qian Wang ◽

Zhiyuan Wu ◽

...

Keyword(s):

Systematic Review ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Meta Analysis ◽

Risk Of Bias ◽

Cochrane Library ◽

Hamilton Depression Scale ◽

High Quality ◽

Conventional Medication

Objective: This systematic review and meta-analysis aimed to assess the effects of the combination of acupuncture-related therapies with conventional medication compared with conventional medication in patients with Parkinson's disease (PD).Methods: A literature search within eight databases [including Medline, Embase, the Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP, and Wanfang Database] was performed covering a time frame from their inception to August 2020. Randomized controlled trials (RCTs) comparing acupuncture-related therapies combined with conventional medication vs. conventional medication in patients with PD were eligible. Two authors independently assessed the risk of bias. Assessments were performed with the total and subscales scores of the Unified Parkinson's Disease Rating Scale (UPDRS), 39-item Parkinson's Disease Questionnaire (PDQ-39), the dosage of Madopar, Mini-Mental State Examination (MMSE), and 17-item Hamilton Depression Scale (HAMD). Data were analyzed by adopting the Cochrane Collaboration's RevMan 5.4 (Review Man, Copenhagen, Denmark); and mean effect sizes and 95% confidence intervals were estimated. Tests for heterogeneity were used to assess differences in treatment effects across different types of acupuncture used.Results: Sixty-six trials met the inclusion criteria, of which 61 trials provided data for the meta-analysis. We defined high-quality articles as those with a low risk of bias in four or more domains; and only 10 (15.15%) articles were of high quality. Compared with the controls, acupuncture-related therapies with conventional medication achieved a benefit in the primary outcomes of UPDRS (motor subscore: −3.90, −4.33 to −3.49, P < 0.01; total score: −7.37 points, −8.91 to −5.82, P < 0.001; activities of daily living subscore: −3.96, −4.96 to −2.95, P < 0.01). For the subgroup difference test among the effects of different acupuncture methods, significant differences existed in outcomes with the UPDRS-III, UPDRS-I, UPDRS-IV, and PDQ-39 scores and Madopar dosage, while non-significant differences existed with the UPDRS-total, UPDRS-II, HAMD, and MMSE scores.Conclusions: Acupuncture-related therapies combined with conventional medication may benefit individuals with PD. Our review findings should be considered with caution because of the methodological weaknesses in the included trials. Future, large randomized trials of acupuncture-related therapies for PD with high methodological quality are warranted.Systematic Review Registration: Identifier CRD42021228110.

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