Nonmotor and diagnostic findings in subjects with de novo Parkinson disease of the DeNoPa cohort

Mollenhauer, Brit; Trautmann, Ellen; Sixel‐Döring, Friederike; Wicke, Tamara; Ebentheuer, Jens; Schaumburg, Martina; Lang, Elisabeth; Focke, Niels K.; Kumar, Kishore R.; Lohmann, Katja; Klein, Christine; Schlossmacher, Michael G.; Kohnen, Ralf; Friede, Tim; Trenkwalder, Claudia

doi:10.1212/wnl.0b013e3182a6cbd5

Cited by 166 publications

(212 citation statements)

References 39 publications

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“…Furthermore, testing for depression, anxiety, and autonomic function demonstrate impairment in PD compared to HC subjects. These findings are consistent with the notion that PD results in widespread nervous system dysfunction even early in the disease course and potentially prior to motor dysfunction 43, 44, 45, 46…”

Section: Discussionsupporting

confidence: 91%

The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort

Marek

Chowdhury

Siderowf

et al. 2018

Ann Clin Transl Neurol

428

339

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ObjectiveThe Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker‐defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease‐modifying therapeutic trials.MethodsA total of 423 untreated PD, 196 Healthy Control (HC) and 64 SWEDD (scans without evidence of dopaminergic deficit) subjects were enrolled at 24 sites. To enroll PD subjects as early as possible following diagnosis, subjects were eligible with only asymmetric bradykinesia or tremor plus a dopamine transporter (DAT) binding deficit on SPECT imaging. Acquisition of data was standardized as detailed at www.ppmi-info.org.ResultsApproximately 9% of enrolled subjects had a single PD sign at baseline. DAT imaging excluded 16% of potential PD subjects with SWEDD. The total MDS‐UPDRS for PD was 32.4 compared to 4.6 for HC and 28.2 for SWEDD. On average, PD subjects demonstrated 45% and 68% reduction in mean striatal and contralateral putamen Specific Binding Ratios (SBR), respectively. Cerebrospinal fluid (CSF) was acquired from >97% of all subjects. CSF (PD/HC/SWEDD pg/mL) α‐synuclein (1845/2204/2141) was reduced in PD vs HC or SWEDD (P < 0.03). Similarly, t‐tau (45/53) and p‐tau (16/18) were reduced in PD versus HC (P < 0.01),Interpretation PPMI has detailed the biomarker signature for an early PD cohort defined by clinical features and imaging biomarkers. This strategy provides the framework to establish biomarker cohorts and to define longitudinal progression biomarkers to support future PD treatment trials.

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Section: Discussionsupporting

confidence: 91%

The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort

Marek

Chowdhury

Siderowf

et al. 2018

Ann Clin Transl Neurol

428

339

View full text Add to dashboard Cite

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“…The study's aim is to improve early diagnosis and to assess proper progression markers, scored at baseline with biannual follow-up. 11 We hypothesized that a composite panel of multimodal progression markers covering overall NMS, cognitive measures, sleep, imaging, and CSF indices would be instructive in understanding the natural history of early PD, and to thereby delineate specific and sensitive outcome measures for future intervention trials. To this end, we applied the same panel of tests to a group of HC to separate PD changes from the process of normal aging.…”

mentioning

confidence: 99%

Monitoring of 30 marker candidates in early Parkinson disease as progression markers

Mollenhauer¹,

Zimmermann²,

et al. 2016

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Objective: This was a longitudinal single-center cohort study to comprehensively explore multimodal progression markers for Parkinson disease (PD) in patients with recently diagnosed PD (n 5 123) and age-matched, neurologically healthy controls (HC; n 5 106).Methods: Thirty tests at baseline and after 24 months covered nonmotor symptoms (NMS), cognitive function, and REM sleep behavior disorder (RBD) by polysomnography (PSG), voxel-based morphometry (VBM) of the brain by MRI, and CSF markers. Linear mixed-effect models were used to estimate differences of rates of change and to provide standardized effect sizes (d) with 95% confidence intervals (CI). Conclusions: Current CSF biomarkers and cognitive scales do not represent useful progression markers. However, sleep and imaging measures, and to some extent NMS, assessed using adequate scales, may be more informative markers to quantify progression. Results:

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“…They continued to show purposeful motor behaviors and/or vocalizations during REM sleep and developed RWA exceeding the validated cutoff value for diagnosis of RBD. 3 They also reported more vivid and elaborate dreams. This supports the hypothesis that RBE is a precursor to RBD.…”

Section: Discussionmentioning

confidence: 99%

“…Maria-Lucia Muntean, MD 1,2 ; Claudia Trenkwalder, MD 1,3 ; Arthur S. Walters, MD 4 ; Brit Mollenhauer, MD 1,3 ; Friederike Sixel-Döring, MD…”

Section: Rem Sleep Behavioral Events and Dreamingmentioning

confidence: 99%

REM Sleep Behavioral Events and Dreaming

Muntean

Trenkwalder

Walters

et al. 2015

Journal of Clinical Sleep Medicine

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Study Objectives: To clarify whether motor behaviors and/ or vocalizations during REM sleep, which do not yet fulfi ll diagnostic criteria for REM sleep behavior disorder (RBD) and were defi ned as REM sleep behavioral events (RBEs), correspond to dream enactments. Methods: 13 subjects (10 patients with Parkinson disease [PD] and 3 healthy controls) originally identifi ed with RBE in a prospective study (DeNoPa cohort) were reinvestigated 2 years later with 2 nights of video-supported polysomnography (vPSG). The fi rst night was used for sleep parameter analysis. During the 2nd night, subjects were awakened and questioned for dream recall and dream content when purposeful motor behaviors and/or vocalizations became evident during REM sleep. REM sleep without atonia (RWA) was analyzed on chin EMG and the cutoff set at 18.2% as specifi c for RBD. Results: At the time of this investigation 9 of 13 subjects with previous RBE were identifi ed with RBD based upon clinical and EMG criteria. All recalled vivid dreams, and 7 subjects were able to describe dream content in detail. Four of 13 subjects with RBE showed RWA values below cutoff values for RBD. Three of these 4 subjects recalled having non-threatening dreams, and 2 (of these 3) were able to describe these dreams in detail. Conclusion: RBE with RWA below the RBD defi ning criteria correlate to dreaming in this selected cohort. There is evidence that RBEs are a precursor to RBD. 1 We found such phenomena in a cohort of de novo patients with Parkinson disease (PD) who had never been treated with medications for PD or RBD, as well as in age-and gender-matched healthy controls (DeNoPa cohort); we termed these phenomena REM sleep behavioral events (RBEs).2 RBEs have been proposed as a new sleep marker for PD and a possible precursor to RBD.2 Whereas RBD is understood as dream enacting behavior, the correlation of RBE to dream mentation has not yet been established. In the study presented here we sought to clarify whether or not RBE also represent dream enacting behaviors and if we can describe specific dream content during these events. METHODSThis study was conducted as an ancillary project to the DeNoPa Kassel study, a longitudinal prospective cohort study of nonmotor symptoms and biomarkers in PD. The design of the entire DeNoPa study, recruitment process and baseline results have been reported elsewhere. 2,3 REM Sleep Behavioral Events and Dreaming S C I E N T I F I C I N V E S T I G AT I O N S Patients and SubjectsWhen this ancillary project was conceived, 13 consecutive subjects (10 patients) from the DeNoPa cohort who showed RBE at baseline were available for re-investigation at their regular 2-year follow-up study visit with 2 nights of videosupported polysomnography (vPSG) (for demographic data see Tables 1A and 1B). At the time of the follow-up study, all 10 PD patients of this cohort were receiving dopaminergic medication. None of the subjects had ever received any medication for RBD. Sleep RecordingsThe fi rst night was documented without awakening and w...

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Nonmotor and diagnostic findings in subjects with de novo Parkinson disease of the DeNoPa cohort

Cited by 166 publications

References 39 publications

The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort

The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort

Monitoring of 30 marker candidates in early Parkinson disease as progression markers

REM Sleep Behavioral Events and Dreaming

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