The fate of patients with REM sleep behavior disorder and mild cognitive impairment

Arnaldi, Dario; Chincarini, A.; Carli, Fabrizio De; Famà, Francesco; Girtler, Nicola; Brugnolo, Andrea; Pardini, Matteo; Massa, Federico; Meli, Riccardo; Schenone, Cristina; Bauckneht, Matteo; Morbelli, Silvia; Nobili, Flavio

doi:10.1016/j.sleep.2020.02.011

Cited by 19 publications

(31 citation statements)

References 22 publications

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“…17 Moreover, several single-center studies found that presynaptic dopaminergic imaging is a good predictor of subsequent phenoconversion of iRBD patients. [18][19][20][21] Finally, a recent international multicenter study, found that nigroputaminal dopaminergic impairment, as investigated by 123 I-FP-CIT-SPECT, is the strongest predictor of phenoconversion in iRBD. 2 Therefore, 123 I-FP-CIT-SPECT is likely going to be used as an enrichment biomarker in upcoming clinical trials in prodromal synucleinopathies.…”

Section: Discussionmentioning

confidence: 98%

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Stratification Tools for Disease‐Modifying Trials in Prodromal Synucleinopathy

et al. 2021

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A BS TRACT: Background: Dopamine transporter single photon-emission computed tomography (DAT-SPECT) is the strongest risk factor for phenoconversion in patients with idiopathic rapid eye movement (REM)sleep behavior disorder (iRBD). However, it might be used as a second-line stratification tool in clinical trials, because it is expensive and mini-invasive. Objective: Aim of the study is to investigate whether other cost-effective and non-invasive biomarkers may be proposed as first-line stratification tools. Methods: Forty-seven consecutive iRBD patients (68.53 AE 7.16 years, 40 males) underwent baseline clinical and neuropsychological assessment, olfaction test, resting electroencephalogram (EEG), and DAT-SPECT. All patients underwent 6 month-based clinical follow-up to investigate the emergence of parkinsonism and/or dementia. Survival analysis and Cox regression were used to estimate conversion risk. Results: Seventeen patients developed an overt synucleinopathy (eight Parkinsonism and nine dementia) 32.8 AE 22 months after diagnosis. The strongest risk factors were putamen specific to non-displaceable binding ratio (SBR) (hazard ratio [HR], 7.3), attention/working memory cognitive function (NPS-AT/WM) (HR, 5.9), EEG occipital mean frequency (HR, 2.7) and clinical motor assessment (HR, 2.3). On multivariate Cox-regression analysis, only putamen SBR and NPS-AT/WM significantly contributed to the model (HR, 6.2, 95% confidence interval [CI], 1.9-19.8). At post-hoc analysis, the trail-making test B (TMT-B) was the single most efficient first-line stratification tool that allowed to reduce the number of eligible subjects to 76.6% (sensitivity 1, specificity 0.37). Combining TMT-B and DAT-SPECT further reduced the sample to 66% (sensitivity 0.88, specificity 0.47). Conclusion:The TMT-B seems to be a cost-effective and efficient first-line screening tool, to be used to select patients that deserve DAT-SPECT as second-line screening tool for disease-modifying clinical trials.

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Section: Discussionmentioning

confidence: 98%

“…Cognitive impairment has been consistently found as a significant risk factor of phenoconversion in iRBD patients 1,2,20,24 . In particular, the TMT‐B has been already proposed as an early diagnostic test for inclusion in clinical trials 25 .…”

Section: Discussionmentioning

confidence: 99%

Stratification Tools for Disease‐Modifying Trials in Prodromal Synucleinopathy

et al. 2021

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“…Abnormal dopamine transporter imaging appears to signal an increased risk of pheno conversion, 1,69,70 especially when combined with cognitive and autonomic impairment. 66,71 Furthermore, nigrostriatal dopamine transporter abnormalities seem to correlate with changes in brain glucose metabolism as assessed by ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET. 72 The ¹⁸F-FDG PET-derived isolated RBD-related (figure 2B) and Parkinson's disease-related pattern 67 appears to be a prodromal progression marker, having shown potential both to assess progression and to predict α-synucleinopathy subtype.…”

Section: Neuroimagingmentioning

confidence: 99%

Biomarkers of conversion to α-synucleinopathy in isolated rapid-eye-movement sleep behaviour disorder

Miglis

Adler

Antelmi

et al. 2021

The Lancet Neurology

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“…Stratification may also be improved by using neuroimaging. For example, DAT‐SPECT studies showed promising results in identifying iRBD patients at high risk of short‐term conversion [23], especially when it is combined with clinical features using a multivariate model [24]. DAT imaging allows the identification of early PD patients with future steeper clinical worsening [25] and the exclusion of subjects without evidence of dopaminergic deficit.…”

Section: Discussionmentioning

confidence: 99%

Rapid eye movement sleep behavior disorder: A proof‐of‐concept neuroprotection study for prodromal synucleinopathies

Arnaldi

Famà

Girtler

et al. 2020

Euro J of Neurology

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Background and purpose To explore the feasibility of a neuroprotection trial in prodromal synucleinopathy, using idiopathic rapid eye movement sleep behavior disorder (iRBD) as the target population and 123I‐FP‐CIT‐SPECT as a biomarker of disease progression. Methods Consecutive iRBD patients were randomly assigned to a treatment arm receiving selegiline and symptomatic rapid eye movement sleep behavior disorder treatment, or to a control arm receiving symptomatic treatment only. Selegiline was chosen because of a demonstrated neuroprotection effect in animal models. Patients underwent 123I‐FP‐CIT‐SPECT at baseline and after 30 months on average. The clinical outcome was the emergence of parkinsonism and/or dementia. A repeated‐measures general linear model (GLM) was applied using group (control and treatment) as ”between” factor, and both time (baseline and follow‐up) and regions (123I‐FP‐CIT‐SPECT putamen and caudate uptake) as the ”within” factors, adjusting for age. Results Thirty iRBD patients completed the study (68.2 ± 6.9 years; 29 males; 21% dropout rate), 13 in the treatment arm, and 17 in the control arm. At follow‐up (29.8 ± 9.0 months), three patients in the control arm developed dementia and one parkinsonism, whereas two patients in the treatment arm developed parkinsonism. Both putamen and caudate uptake decreased over time in the control arm. In the treatment arm, only the putamen uptake decreased over time, whereas caudate uptake remained stable. GLM analysis demonstrated an effect of treatment on the 123I‐FP‐CIT‐SPECT uptake change, with a significant interaction between the effect of group, time, and regions (p = 0.004). Conclusions A 30‐months neuroprotection study for prodromal synucleinopathy is feasible, using iRBD as the target population and 123I‐FP‐CIT‐SPECT as a biomarker of disease progression.

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The fate of patients with REM sleep behavior disorder and mild cognitive impairment

Cited by 19 publications

References 22 publications

Stratification Tools for Disease‐Modifying Trials in Prodromal Synucleinopathy

Stratification Tools for Disease‐Modifying Trials in Prodromal Synucleinopathy

Biomarkers of conversion to α-synucleinopathy in isolated rapid-eye-movement sleep behaviour disorder

Rapid eye movement sleep behavior disorder: A proof‐of‐concept neuroprotection study for prodromal synucleinopathies

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