The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Ronald B Postuma - One of the best experts on this subject based on the ideXlab platform.
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risk and predictors of dementia and Parkinsonism in idiopathic rem sleep behaviour disorder a multicentre study
Brain, 2019Co-Authors: Ronald B Postuma, Alex Iranzo, Michele T M Hu, Birgit Hogl, Bradley F Boeve, R Manni, Wolfgang H Oertel, Isabelle Arnulf, Luigi Ferinistrambi, Monica PulighedduAbstract:Idiopathic REM sleep behaviour disorder (iRBD) is a powerful early sign of Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. This provides an unprecedented opportunity to directly observe prodromal neurodegenerative states, and potentially intervene with neuroprotective therapy. For future neuroprotective trials, it is essential to accurately estimate phenoconversion rate and identify potential predictors of phenoconversion. This study assessed the neurodegenerative disease risk and predictors of neurodegeneration in a large multicentre cohort of iRBD. We combined prospective follow-up data from 24 centres of the International RBD Study Group. At baseline, patients with polysomnographically-confirmed iRBD without Parkinsonism or dementia underwent sleep, motor, cognitive, autonomic and special sensory testing. Patients were then prospectively followed, during which risk of dementia and parkinsonsim were assessed. The risk of dementia and Parkinsonism was estimated with Kaplan-Meier analysis. Predictors of phenoconversion were assessed with Cox proportional hazards analysis, adjusting for age, sex, and centre. Sample size estimates for disease-modifying trials were calculated using a time-to-event analysis. Overall, 1280 patients were recruited. The average age was 66.3 ± 8.4 and 82.5% were male. Average follow-up was 4.6 years (range = 1–19 years). The overall conversion rate from iRBD to an overt neurodegenerative syndrome was 6.3% per year, with 73.5% converting after 12-year follow-up. The rate of phenoconversion was significantly increased with abnormal quantitative motor testing [hazard ratio (HR) = 3.16], objective motor examination (HR = 3.03), olfactory deficit (HR = 2.62), mild cognitive impairment (HR = 1.91–2.37), erectile dysfunction (HR = 2.13), motor symptoms (HR = 2.11), an abnormal DAT scan (HR = 1.98), colour vision abnormalities (HR = 1.69), constipation (HR = 1.67), REM atonia loss (HR = 1.54), and age (HR = 1.54). There was no significant predictive value of sex, daytime somnolence, insomnia, restless legs syndrome, sleep apnoea, urinary dysfunction, orthostatic symptoms, depression, anxiety, or hyperechogenicity on substantia nigra ultrasound. Among predictive markers, only cognitive variables were different at baseline between those converting to primary dementia versus Parkinsonism. Sample size estimates for definitive neuroprotective trials ranged from 142 to 366 patients per arm. This large multicentre study documents the high phenoconversion rate from iRBD to an overt neurodegenerative syndrome. Our findings provide estimates of the relative predictive value of prodromal markers, which can be used to stratify patients for neuroprotective trials.
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association between poor cognitive functioning and risk of incident Parkinsonism the rotterdam study
JAMA Neurology, 2017Co-Authors: Sirwan K L Darweesh, Frank J Wolters, Ronald B Postuma, Bruno H Stricker, Albert Hofman, Peter J Koudstaal, Kamran M IkramAbstract:Importance Cognitive dysfunction is a common feature among patients with Parkinsonism, including Parkinson disease (PD). However, there is a scarcity of data on cognitive functioning before Parkinsonism diagnosis, a stage at which patients may still respond to putative disease-modifying interventions. Objective To assess whether poor cognitive functioning is associated with an increased risk of Parkinsonism. Design, Setting, and Participants Between January 8, 2002, and December 14, 2008, baseline cognitive function was assessed in 7386 participants of the Rotterdam Study who were free of Parkinsonism and dementia. Four tests were administered (Stroop color word test, letter-digit substitution, verbal fluency, and word learning) and a global cognition score was derived from principal component analysis. Subsequently, participants were followed up until January 1, 2015, for the onset of Parkinsonism through serial in-person examinations and complete access to medical records. Parkinsonism was defined as the (1) presence of hypokinesia or bradykinesia plus at least 1 other cardinal sign and/or (2) clinical diagnosis by a neurologist or geriatrician. Patients with dementia diagnosis before Parkinsonism diagnosis were considered to have probable PD. Main Outcomes and Measures Hazard ratios (HRs) for incident Parkinsonism per SD decrease in global cognition, adjusted for age, sex, and study subcohort. Results A total of 7386 patients were included in the analysis; of these, 4236 (57.4%) were women and mean (SD) age was 65.3 (10.2) years. During follow-up (median, 8.3 years; range, 0-15 years), 79 (1.1%) individuals received a diagnosis of incident Parkinsonism; of these, 57 (72.2%) received a diagnosis of probable PD. Among patients with incident Parkinsonism, 24 (30.4%) also developed dementia (10 before and 14 after Parkinsonism onset). Poor global cognition at baseline was associated with a higher hazard of incident Parkinsonism (hazard ratio [HR], 1.79; 95% CI, 1.37-2.33). The association remained robust beyond the first 8 years (HR, 1.59; 95% CI, 1.01-2.59) and after removing individuals with dementia onset before Parkinsonism (HR, 1.72; 95% CI, 1.28-2.27). Poor global cognition at baseline was also associated with incident probable PD (HR, 1.52; 95% CI, 1.11-2.08). Letter-digit substitution (HR, 1.59; 95% CI, 1.22-2.04), verbal fluency (HR, 1.61; 95% CI, 1.23-2.08), and inverted interference task Stroop color word test (HR, 1.56; 95% CI, 1.25-1.96) scores were each associated with incident Parkinsonism, whereas the association with word learning delayed-task scores was weaker (HR, 1.18; 95% CI, 0.92-1.52). Conclusions and Relevance Poor cognitive functioning is associated with an increased risk of incident Parkinsonism, including probable PD. Cognition indicates the probability of Parkinsonism over long intervals and extends beyond patients with onset of Parkinsonism after dementia. The findings suggest that cognitive dysfunction can be considered a sign of prodromal PD.
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how does Parkinsonism start prodromal Parkinsonism motor changes in idiopathic rem sleep behaviour disorder
Brain, 2012Co-Authors: Ronald B Postuma, Anthony E Lang, Jeanfrancois Gagnon, Amelie Pelletier, Jacques MontplaisirAbstract:Parkinsonism, as a gradually progressive disorder, has a prodromal interval during which neurodegeneration has begun but cardinal manifestations have not fully developed. A systematic direct assessment of this interval has never been performed. Since patients with idiopathic REM sleep behaviour disorder are at very high risk of Parkinsonism, they provide a unique opportunity to observe directly the development of Parkinsonism. Patients with idiopathic REM sleep behaviour disorder in an ongoing cohort study were evaluated annually with several quantitative motor measures, including the Unified Parkinson’s Disease Rating Scale, Purdue Pegboard, alternate-tap test and timed up-and-go. Patients who developed Parkinsonism were identified from this cohort and matched according to age to normal controls. Their results on motor testing from the preceding years were plotted, and then assessed with regression analysis, to determine when markers first deviated from normal values. Sensitivity and specificity of quantitative motor markers for diagnosing prodromal Parkinsonism were assessed. Of 78 patients, 20 developed Parkinsonism. On regression analysis, the Unified Parkinson’s Disease Rating Scale first intersected normal values at an estimated 4.5 years before diagnosis. Voice and face akinesia intersected earliest (estimated prodromal interval = 9.8 years), followed by rigidity (4.4 years), gait abnormalities (4.4 years) and limb bradykinesia (4.2 years). Quantitative motor tests intersected normal values at longer prodromal intervals than subjective examination (Purdue Pegboard = 8.6 years, alternate-tap = 8.2, timed up-and-go = 6.3). Using Purdue Pegboard and the alternate-tap test, Parkinsonism could be detected with 71–82% sensitivity and specificity 3 years before diagnosis, whereas a Unified Parkinson’s Disease Rating Scale score >4 identified prodromal Parkinsonism with 88% sensitivity and 94% specificity 2 years before diagnosis. Removal of action tremor scores improved sensitivity to 94% and specificity to 97% at 2 years before diagnosis (cut-off >3). Although distinction between conditions was often difficult, prodromal dementia with Lewy bodies appeared to have a slower progression than Parkinson’s disease (prodromal interval = 6.0 versus 3.8 years). Using a cut-off of Unified Parkinson’s Disease Rating Scale >3 (excluding action tremor), 25% of patients with ‘still-idiopathic’ REM sleep behaviour disorder demonstrated evidence of possible prodromal Parkinsonism. Therefore, using direct assessment of motor examination before Parkinsonism in a REM sleep behaviour disorder, we have estimated a prodromal interval of ∼4.5 years on the Unified Parkinson’s Disease Rating Scale; other quantitative markers may detect Parkinsonism earlier. Simple quantitative motor measures may be capable of reliably detecting Parkinsonism, even before a clinical diagnosis can be made by experienced movement disorders neurologists. * Abbreviations : AUC : area under the curve UPDRS : Unified Parkinson’s Disease Rating Scale
Jacques Montplaisir - One of the best experts on this subject based on the ideXlab platform.
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how does Parkinsonism start prodromal Parkinsonism motor changes in idiopathic rem sleep behaviour disorder
Brain, 2012Co-Authors: Ronald B Postuma, Anthony E Lang, Jeanfrancois Gagnon, Amelie Pelletier, Jacques MontplaisirAbstract:Parkinsonism, as a gradually progressive disorder, has a prodromal interval during which neurodegeneration has begun but cardinal manifestations have not fully developed. A systematic direct assessment of this interval has never been performed. Since patients with idiopathic REM sleep behaviour disorder are at very high risk of Parkinsonism, they provide a unique opportunity to observe directly the development of Parkinsonism. Patients with idiopathic REM sleep behaviour disorder in an ongoing cohort study were evaluated annually with several quantitative motor measures, including the Unified Parkinson’s Disease Rating Scale, Purdue Pegboard, alternate-tap test and timed up-and-go. Patients who developed Parkinsonism were identified from this cohort and matched according to age to normal controls. Their results on motor testing from the preceding years were plotted, and then assessed with regression analysis, to determine when markers first deviated from normal values. Sensitivity and specificity of quantitative motor markers for diagnosing prodromal Parkinsonism were assessed. Of 78 patients, 20 developed Parkinsonism. On regression analysis, the Unified Parkinson’s Disease Rating Scale first intersected normal values at an estimated 4.5 years before diagnosis. Voice and face akinesia intersected earliest (estimated prodromal interval = 9.8 years), followed by rigidity (4.4 years), gait abnormalities (4.4 years) and limb bradykinesia (4.2 years). Quantitative motor tests intersected normal values at longer prodromal intervals than subjective examination (Purdue Pegboard = 8.6 years, alternate-tap = 8.2, timed up-and-go = 6.3). Using Purdue Pegboard and the alternate-tap test, Parkinsonism could be detected with 71–82% sensitivity and specificity 3 years before diagnosis, whereas a Unified Parkinson’s Disease Rating Scale score >4 identified prodromal Parkinsonism with 88% sensitivity and 94% specificity 2 years before diagnosis. Removal of action tremor scores improved sensitivity to 94% and specificity to 97% at 2 years before diagnosis (cut-off >3). Although distinction between conditions was often difficult, prodromal dementia with Lewy bodies appeared to have a slower progression than Parkinson’s disease (prodromal interval = 6.0 versus 3.8 years). Using a cut-off of Unified Parkinson’s Disease Rating Scale >3 (excluding action tremor), 25% of patients with ‘still-idiopathic’ REM sleep behaviour disorder demonstrated evidence of possible prodromal Parkinsonism. Therefore, using direct assessment of motor examination before Parkinsonism in a REM sleep behaviour disorder, we have estimated a prodromal interval of ∼4.5 years on the Unified Parkinson’s Disease Rating Scale; other quantitative markers may detect Parkinsonism earlier. Simple quantitative motor measures may be capable of reliably detecting Parkinsonism, even before a clinical diagnosis can be made by experienced movement disorders neurologists. * Abbreviations : AUC : area under the curve UPDRS : Unified Parkinson’s Disease Rating Scale
Amelie Pelletier - One of the best experts on this subject based on the ideXlab platform.
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how does Parkinsonism start prodromal Parkinsonism motor changes in idiopathic rem sleep behaviour disorder
Brain, 2012Co-Authors: Ronald B Postuma, Anthony E Lang, Jeanfrancois Gagnon, Amelie Pelletier, Jacques MontplaisirAbstract:Parkinsonism, as a gradually progressive disorder, has a prodromal interval during which neurodegeneration has begun but cardinal manifestations have not fully developed. A systematic direct assessment of this interval has never been performed. Since patients with idiopathic REM sleep behaviour disorder are at very high risk of Parkinsonism, they provide a unique opportunity to observe directly the development of Parkinsonism. Patients with idiopathic REM sleep behaviour disorder in an ongoing cohort study were evaluated annually with several quantitative motor measures, including the Unified Parkinson’s Disease Rating Scale, Purdue Pegboard, alternate-tap test and timed up-and-go. Patients who developed Parkinsonism were identified from this cohort and matched according to age to normal controls. Their results on motor testing from the preceding years were plotted, and then assessed with regression analysis, to determine when markers first deviated from normal values. Sensitivity and specificity of quantitative motor markers for diagnosing prodromal Parkinsonism were assessed. Of 78 patients, 20 developed Parkinsonism. On regression analysis, the Unified Parkinson’s Disease Rating Scale first intersected normal values at an estimated 4.5 years before diagnosis. Voice and face akinesia intersected earliest (estimated prodromal interval = 9.8 years), followed by rigidity (4.4 years), gait abnormalities (4.4 years) and limb bradykinesia (4.2 years). Quantitative motor tests intersected normal values at longer prodromal intervals than subjective examination (Purdue Pegboard = 8.6 years, alternate-tap = 8.2, timed up-and-go = 6.3). Using Purdue Pegboard and the alternate-tap test, Parkinsonism could be detected with 71–82% sensitivity and specificity 3 years before diagnosis, whereas a Unified Parkinson’s Disease Rating Scale score >4 identified prodromal Parkinsonism with 88% sensitivity and 94% specificity 2 years before diagnosis. Removal of action tremor scores improved sensitivity to 94% and specificity to 97% at 2 years before diagnosis (cut-off >3). Although distinction between conditions was often difficult, prodromal dementia with Lewy bodies appeared to have a slower progression than Parkinson’s disease (prodromal interval = 6.0 versus 3.8 years). Using a cut-off of Unified Parkinson’s Disease Rating Scale >3 (excluding action tremor), 25% of patients with ‘still-idiopathic’ REM sleep behaviour disorder demonstrated evidence of possible prodromal Parkinsonism. Therefore, using direct assessment of motor examination before Parkinsonism in a REM sleep behaviour disorder, we have estimated a prodromal interval of ∼4.5 years on the Unified Parkinson’s Disease Rating Scale; other quantitative markers may detect Parkinsonism earlier. Simple quantitative motor measures may be capable of reliably detecting Parkinsonism, even before a clinical diagnosis can be made by experienced movement disorders neurologists. * Abbreviations : AUC : area under the curve UPDRS : Unified Parkinson’s Disease Rating Scale
Sirwan K L Darweesh - One of the best experts on this subject based on the ideXlab platform.
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sleep and risk of Parkinsonism and parkinson s disease a population based study
Brain, 2019Co-Authors: Thom S. Lysen, Sirwan K L Darweesh, Kamran M Ikram, Annemarie I. Luik, Arfan M IkramAbstract:Sleep disturbances may signal presence of prodromal Parkinsonism, including Parkinson’s disease. Whether general sleep quality or duration in otherwise healthy subjects is related to the risk of Parkinsonism remains unclear. We hypothesized that both worse self-reported sleep quality and duration, as well as a longitudinal deterioration in these measures, are associated with the risk of Parkinsonism, including Parkinson’s disease. In the prospective population-based Rotterdam Study, we assessed sleep quality and duration with the Pittsburgh Sleep Quality Index in 7726 subjects (mean age 65 years, 57% female) between 2002 and 2008, and again in 5450 subjects between 2009 and 2014. Participants were followed until 2015 for a diagnosis of Parkinsonism and Parkinson’s disease. Outcomes were assessed using multiple modalities: interviews, physical examination, and continuous monitoring of pharmacy records and medical records of general practitioners. We used Cox regression to associate sleep, and changes in sleep over time, with incident Parkinsonism and Parkinson’s disease, adjusting for age, sex, education and smoking status. Over 64 855 person-years in 13 years of follow-up (mean: 8.4 years), 75 participants developed Parkinsonism, of whom 47 developed Parkinson’s disease. We showed that within the first 2 years of followup, worse sleep quality {hazard ratio (HR) 2.38 per standard deviation increase [95% confidence interval (CI 0.91–6.23)]} and shorter sleep duration [HR 0.61 per standard deviation increase (95% CI 0.31–1.21)] related to a higher risk of Parkinsonism. Associations of worse sleep quality [HR 3.86 (95% CI 1.19–12.47)] and shorter sleep duration [HR 0.48 (95% CI 0.23–0.99)] with Parkinson’s disease were more pronounced, and statistically significant, compared to Parkinsonism. This increased risk disappeared with longer follow-up duration. Worsening of sleep quality [HR 1.76 per standard deviation increase (95% CI 1.12–2.78)], as well as shortening of sleep duration [HR 1.72 per standard deviation decrease (95% CI 1.08–2.72)], were related to Parkinson’s disease risk in the subsequent 6 years. Therefore, we argue that in the general population, deterioration of sleep quality and duration are markers of the prodromal phase of Parkinsonism, including Parkinson’s disease.
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Sleep and risk of Parkinsonism and Parkinson’s disease: a population-based study
Brain, 2019Co-Authors: Thom S. Lysen, Sirwan K L Darweesh, M. Kamran Ikram, Annemarie I. LuikAbstract:Sleep disturbances may signal presence of prodromal Parkinsonism, including Parkinson’s disease. Whether general sleep quality or duration in otherwise healthy subjects is related to the risk of Parkinsonism remains unclear. We hypothesized that both worse self-reported sleep quality and duration, as well as a longitudinal deterioration in these measures, are associated with the risk of Parkinsonism, including Parkinson’s disease. In the prospective population-based Rotterdam Study, we assessed sleep quality and duration with the Pittsburgh Sleep Quality Index in 7726 subjects (mean age 65 years, 57% female) between 2002 and 2008, and again in 5450 subjects between 2009 and 2014. Participants were followed until 2015 for a diagnosis of Parkinsonism and Parkinson’s disease. Outcomes were assessed using multiple modalities: interviews, physical examination, and continuous monitoring of pharmacy records and medical records of general practitioners. We used Cox regression to associate sleep, and changes in sleep over time, with incident Parkinsonism and Parkinson’s disease, adjusting for age, sex, education and smoking status. Over 64 855 person-years in 13 years of follow-up (mean: 8.4 years), 75 participants developed Parkinsonism, of whom 47 developed Parkinson’s disease. We showed that within the first 2 years of followup, worse sleep quality {hazard ratio (HR) 2.38 per standard deviation increase [95% confidence interval (CI 0.91–6.23)]} and shorter sleep duration [HR 0.61 per standard deviation increase (95% CI 0.31–1.21)] related to a higher risk of Parkinsonism. Associations of worse sleep quality [HR 3.86 (95% CI 1.19–12.47)] and shorter sleep duration [HR 0.48 (95% CI 0.23–0.99)] with Parkinson’s disease were more pronounced, and statistically significant, compared to Parkinsonism. This increased risk disappeared with longer follow-up duration. Worsening of sleep quality [HR 1.76 per standard deviation increase (95% CI 1.12–2.78)], as well as shortening of sleep duration [HR 1.72 per standard deviation decrease (95% CI 1.08–2.72)], were related to Parkinson’s disease risk in the subsequent 6 years. Therefore, we argue that in the general population, deterioration of sleep quality and duration are markers of the prodromal phase of Parkinsonism, including Parkinson’s disease.
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association between poor cognitive functioning and risk of incident Parkinsonism the rotterdam study
JAMA Neurology, 2017Co-Authors: Sirwan K L Darweesh, Frank J Wolters, Ronald B Postuma, Bruno H Stricker, Albert Hofman, Peter J Koudstaal, Kamran M IkramAbstract:Importance Cognitive dysfunction is a common feature among patients with Parkinsonism, including Parkinson disease (PD). However, there is a scarcity of data on cognitive functioning before Parkinsonism diagnosis, a stage at which patients may still respond to putative disease-modifying interventions. Objective To assess whether poor cognitive functioning is associated with an increased risk of Parkinsonism. Design, Setting, and Participants Between January 8, 2002, and December 14, 2008, baseline cognitive function was assessed in 7386 participants of the Rotterdam Study who were free of Parkinsonism and dementia. Four tests were administered (Stroop color word test, letter-digit substitution, verbal fluency, and word learning) and a global cognition score was derived from principal component analysis. Subsequently, participants were followed up until January 1, 2015, for the onset of Parkinsonism through serial in-person examinations and complete access to medical records. Parkinsonism was defined as the (1) presence of hypokinesia or bradykinesia plus at least 1 other cardinal sign and/or (2) clinical diagnosis by a neurologist or geriatrician. Patients with dementia diagnosis before Parkinsonism diagnosis were considered to have probable PD. Main Outcomes and Measures Hazard ratios (HRs) for incident Parkinsonism per SD decrease in global cognition, adjusted for age, sex, and study subcohort. Results A total of 7386 patients were included in the analysis; of these, 4236 (57.4%) were women and mean (SD) age was 65.3 (10.2) years. During follow-up (median, 8.3 years; range, 0-15 years), 79 (1.1%) individuals received a diagnosis of incident Parkinsonism; of these, 57 (72.2%) received a diagnosis of probable PD. Among patients with incident Parkinsonism, 24 (30.4%) also developed dementia (10 before and 14 after Parkinsonism onset). Poor global cognition at baseline was associated with a higher hazard of incident Parkinsonism (hazard ratio [HR], 1.79; 95% CI, 1.37-2.33). The association remained robust beyond the first 8 years (HR, 1.59; 95% CI, 1.01-2.59) and after removing individuals with dementia onset before Parkinsonism (HR, 1.72; 95% CI, 1.28-2.27). Poor global cognition at baseline was also associated with incident probable PD (HR, 1.52; 95% CI, 1.11-2.08). Letter-digit substitution (HR, 1.59; 95% CI, 1.22-2.04), verbal fluency (HR, 1.61; 95% CI, 1.23-2.08), and inverted interference task Stroop color word test (HR, 1.56; 95% CI, 1.25-1.96) scores were each associated with incident Parkinsonism, whereas the association with word learning delayed-task scores was weaker (HR, 1.18; 95% CI, 0.92-1.52). Conclusions and Relevance Poor cognitive functioning is associated with an increased risk of incident Parkinsonism, including probable PD. Cognition indicates the probability of Parkinsonism over long intervals and extends beyond patients with onset of Parkinsonism after dementia. The findings suggest that cognitive dysfunction can be considered a sign of prodromal PD.
Monica Puligheddu - One of the best experts on this subject based on the ideXlab platform.
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risk and predictors of dementia and Parkinsonism in idiopathic rem sleep behaviour disorder a multicentre study
Brain, 2019Co-Authors: Ronald B Postuma, Alex Iranzo, Michele T M Hu, Birgit Hogl, Bradley F Boeve, R Manni, Wolfgang H Oertel, Isabelle Arnulf, Luigi Ferinistrambi, Monica PulighedduAbstract:Idiopathic REM sleep behaviour disorder (iRBD) is a powerful early sign of Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. This provides an unprecedented opportunity to directly observe prodromal neurodegenerative states, and potentially intervene with neuroprotective therapy. For future neuroprotective trials, it is essential to accurately estimate phenoconversion rate and identify potential predictors of phenoconversion. This study assessed the neurodegenerative disease risk and predictors of neurodegeneration in a large multicentre cohort of iRBD. We combined prospective follow-up data from 24 centres of the International RBD Study Group. At baseline, patients with polysomnographically-confirmed iRBD without Parkinsonism or dementia underwent sleep, motor, cognitive, autonomic and special sensory testing. Patients were then prospectively followed, during which risk of dementia and parkinsonsim were assessed. The risk of dementia and Parkinsonism was estimated with Kaplan-Meier analysis. Predictors of phenoconversion were assessed with Cox proportional hazards analysis, adjusting for age, sex, and centre. Sample size estimates for disease-modifying trials were calculated using a time-to-event analysis. Overall, 1280 patients were recruited. The average age was 66.3 ± 8.4 and 82.5% were male. Average follow-up was 4.6 years (range = 1–19 years). The overall conversion rate from iRBD to an overt neurodegenerative syndrome was 6.3% per year, with 73.5% converting after 12-year follow-up. The rate of phenoconversion was significantly increased with abnormal quantitative motor testing [hazard ratio (HR) = 3.16], objective motor examination (HR = 3.03), olfactory deficit (HR = 2.62), mild cognitive impairment (HR = 1.91–2.37), erectile dysfunction (HR = 2.13), motor symptoms (HR = 2.11), an abnormal DAT scan (HR = 1.98), colour vision abnormalities (HR = 1.69), constipation (HR = 1.67), REM atonia loss (HR = 1.54), and age (HR = 1.54). There was no significant predictive value of sex, daytime somnolence, insomnia, restless legs syndrome, sleep apnoea, urinary dysfunction, orthostatic symptoms, depression, anxiety, or hyperechogenicity on substantia nigra ultrasound. Among predictive markers, only cognitive variables were different at baseline between those converting to primary dementia versus Parkinsonism. Sample size estimates for definitive neuroprotective trials ranged from 142 to 366 patients per arm. This large multicentre study documents the high phenoconversion rate from iRBD to an overt neurodegenerative syndrome. Our findings provide estimates of the relative predictive value of prodromal markers, which can be used to stratify patients for neuroprotective trials.
