Predictive markers for early conversion of iRBD to neurodegenerative synucleinopathy diseases

Li, Yuanyuan; Kang, Wenyan; Yang, Qiong; Zhang, Lina; Zhang, Linyuan; Dong, Fangyi; Chen, Shengdi; Li, Jun

doi:10.1212/wnl.0000000000003838

Cited by 87 publications

(68 citation statements)

References 37 publications

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“…The first neuroimaging marker prospectively proven to predict PD was described only as recently as 2010, when Iranzo and colleagues documented that dopaminergic functional imaging predicted neurodegeneration among patients with idiopathic RBD . This was confirmed in a second RBD cohort . Predictive value was confirmed in a non‐RBD population only in 2017, with the PARS study.…”

Section: Key Advances In the Last Decadementioning

confidence: 99%

Prodromal Parkinson's Disease: The Decade Past, the Decade to Come

2019

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The past decade has seen a dramatic expansion of the field of prodromal PD. Ten years ago, there were only six known prodromal markers of disease, none of which had more than two studies documenting diagnostic value. We now have at least 16 markers, with as many as 10 prospective studies for a single marker. This review summarizes the major advances over the last decade and speculates about the advances we will see in the decade to come. The most notable advances over the last decade came through the study of high‐risk cohorts (REM sleep behavior disorder and later genetic and autonomic cohorts), the generation of more representative population‐based cohorts for studying prodromal PD, major advances in neuroimaging of early disease stages, the emerging likelihood that tissue biopsy will be able to diagnose prodromal PD, and the coalescence of prodromal markers into discrete criteria. As the next decade dawns, we await increasing precision of sensitivity and specificity estimates of known markers, the discovery of new biomarkers of prodromal disease, improvements in diagnosis using combined methods/criteria (with increasing recognition of prodromal PD as one stage of the full PD spectrum), and ultimately the development of neuroprotective therapy that can be provided at the earliest stages of disease. © 2019 International Parkinson and Movement Disorder Society

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Section: Key Advances In the Last Decadementioning

confidence: 99%

Prodromal Parkinson's Disease: The Decade Past, the Decade to Come

2019

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“…A recent Chinese study comparing patients with iRBD to PD and controls found both motor and non‐motor deficits in patients with iRBD 69 . Involvement of olfaction, gastrointestinal, and cardiovascular functions has been confirmed in other studies of iRBD and found to be predictive of impending conversion to neurodegenerative disease 70 , 71 …”

Section: Idiopathic Rbd As a Predictor Of Neurodegenerationmentioning

confidence: 87%

REM sleep behaviour disorder: not just a bad dream

Matar

Lewis

2017

Medical Journal of Australia

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Rapid eye movement (REM) sleep behaviour disorder (RBD) is a parasomnia characterised by the loss of the normal atonia during the REM stage of sleep, resulting in overt motor behaviours that usually represent the enactment of dreams. Patients will seek medical attention due to sleep-related injuries or unpleasant dream content. Idiopathic RBD which occurs independently of any other disease occurs in up to 2% of the older population. Meanwhile, secondary RBD is very common in association with certain neurodegenerative conditions. RBD can also occur in the context of antidepressant use, obstructive sleep apnoea and narcolepsy. RBD can be diagnosed with a simple screening question followed by confirmation with polysomnography to exclude potential mimics. Treatment for RBD is effective and involves treatment of underlying causes, modification of the sleep environment, and pharmacotherapy with either clonazepam or melatonin. An important finding in the past decade is the recognition that almost all patients with idiopathic RBD will ultimately go on to develop Parkinson disease or dementia with Lewy bodies. This suggests that idiopathic RBD represents a prodromal phase of these conditions. Physicians should be aware of the risk of phenoconversion. They should educate idiopathic RBD patients to recognise the symptoms of these conditions and refer as appropriate for further testing and enrolment into research trials focused on neuroprotective measures.

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“…However, progression in the prodromal phase is an even greater challenge, as there are currently no clinical or biochemical markers to predict who will convert and when. First studies imply that imaging markers may be helpful to better understand individual progression of the neurodegenerative process with Dopamin‐Transporter‐Imaging using single photon emission computed tomography (DATScan) being promising for individuals close to motor manifestation . Still, long follow‐ups will be needed for clinical studies making this rather complex and costly imaging tool unlikely to be implemented in the routine for application in the general population.…”

Section: Discussionmentioning

confidence: 99%

“…First studies imply that imaging markers may be helpful to better understand individual progression of the neurodegenerative process with Dopamin-Transporter-Imaging using single photon emission computed tomography (DATScan) being promising for individuals close to motor manifestation. 90,91 Still, long follow-ups will be needed for clinical studies making this rather complex and costly imaging tool unlikely to be implemented in the routine for application in the general population. Magnetic resonance imaging markers, which are increasingly promising on a group level as biomarkers for a prodromal state, have not classified as progression markers yet.…”

Section: Targets From Epidemiological Studies and Symptomatic Therapymentioning

confidence: 99%

Progress of Pharmacological Approaches in Parkinson's Disease

Zeuner

Schäffer

Hopfner

et al. 2019

Clin Pharma and Therapeutics

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The progressive neurodegenerative process in Parkinson's disease (PD) is not restricted to dopaminergic midbrain neurons but involves the entire nervous system. In this review, we outline established treatment options at different disease stages and address new therapeutic approaches. These include, based on recent advances in the understanding of the pathophysiology of PD, genetic and disease‐modifying approaches to reduce abnormal accumulation and aggregation of alpha‐synuclein (aSYN), mitochondrial dysfunction, and dysfunction of lysosomal proteins. Moreover, we highlight clinical trials to reduce neuroinflammation and increase neurorestoration.

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Predictive markers for early conversion of iRBD to neurodegenerative synucleinopathy diseases

Abstract: Our findings elucidate the predictive value of autonomic dysfunction and DAT uptake in identifying patients with iRBD at a high risk of progressing into neurodegenerative synucleinopathy diseases and could form a basis for future disease-prevention trials.

Cited by 87 publications

References 37 publications

Prodromal Parkinson's Disease: The Decade Past, the Decade to Come

Prodromal Parkinson's Disease: The Decade Past, the Decade to Come

REM sleep behaviour disorder: not just a bad dream

Progress of Pharmacological Approaches in Parkinson's Disease

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