PMC:4927924 / 11625-15922 JSONTXT

{"project":"TEST0","denotations":[{"id":"26485429-132-138-1671226","span":{"begin":166,"end":168},"obj":"[\"3505730\"]"},{"id":"26485429-73-79-1671227","span":{"begin":363,"end":365},"obj":"[\"16632313\"]"},{"id":"26485429-210-216-1671228","span":{"begin":578,"end":580},"obj":"[\"26208108\"]"},{"id":"26485429-208-214-1671229","span":{"begin":1106,"end":1108},"obj":"[\"23562390\"]"},{"id":"26485429-197-203-1671230","span":{"begin":1393,"end":1395},"obj":"[\"25767079\"]"},{"id":"26485429-235-241-1671231","span":{"begin":1959,"end":1961},"obj":"[\"25767079\"]"},{"id":"26485429-107-113-1671232","span":{"begin":2792,"end":2794},"obj":"[\"23562390\"]"},{"id":"26485429-181-187-1671233","span":{"begin":3029,"end":3031},"obj":"[\"25609758\"]"},{"id":"26485429-236-242-1671234","span":{"begin":3885,"end":3887},"obj":"[\"25609758\"]"},{"id":"26485429-234-240-1671235","span":{"begin":4293,"end":4295},"obj":"[\"25681454\"]"}],"text":"REM-sleep behavior disorder (RBD)\nRBD is a parasomnia clinically characterized by dream-enacting behaviours related to loss of physiological atonia during REM-sleep [59]. The prevalence of idiopathic RBD in the population is not well defined as definite diagnosis requires polysomnography. A commonly cited figure of 0.4% , however, may well be an underestimate [60]. Indeed, when using two validated screening questionnaires in an elderly population-based sample of 476 subjects, we recently found a prevalence of probable RBD of 5–8% in a Caucasian population aged \u003e60 years [61]. In this particular cross sectional study, probable RBD was associated with multiple other nonmotor markers of PD, while polysomnography was not available. Idiopathic RBD is increasingly recognized as a harbinger of neurodegenerative diseases, including not only PD but also other synucleinopathies like DLB or MSA. Several follow-up studies have found that the majority of subjects with idiopathic RBD (\u003e80%) will convert into one of these disorders –most commonly PD or DLB - with extended follow-up over decades [15, 54, 62]. Two recent prospective cohort studies have further substantiated these observations. Postuma and colleagues collected follow-up data in a multicentre sample of 305 patients with idiopathic RBD over up to 6 years and found an overall conversion to neurodegenerative diseases of 33% [63], which was time-dependent at 15% after 2 years, 25% after 3 years, and 41% after 5 years. Conversion to PD or DLB was common (42% and 50% , respectively), while only 8% converted to MSA. Idiopathic RBD patient who converted over the observational period were older, more likely to report a family history of dementia, and more frequently endorsed autonomic and/or motor symptoms on questionnaires compared to those who remained disease free, whereas many baseline characteristics including caffeine and nicotine exposure were not different between these groups [63]. With the aid of thorough testing batteries, conversion from RBD to PD or PD Dementia/DLB appears to be more predictable. One recent prospective study in 89 idiopathic RBD patients found that smell identification loss (hazard ratio (HR) 2.8), abnormal colour vision (HR, 3.1), and subtle motor impairment (HR, 3.9), as well as advanced age (HR, 1.1) and non-use of anti-depressants (HR, 3.5) was associated with conversion to one of these synucleinopathies (including MSA) over the 7.5 year observational period.\nTaken together, current evidence shows that RBD is the most specific among the different risk factors for PD (see Table 2) and RBD cohorts seem obvious candidates for future disease-prevention studies for PD. However, the median latency to conversion into clinically defined PD can be as long as 12 to 14 years [15, 54], seriously limiting the feasibility of such trials. Therefore, we recently investigated whether olfactory impairment can predict early conversion to PD or PDD/DLB among 35 idiopathic RBD patients prospectively followed over 5 years [58]. Indeed, abnormal baseline performance on the multidimensional SniffinSticks test assessing odour identification, odour discrimination, and olfactory threshold predicted conversion to a Lewy body disorder with an accuracy of 82.4% , and this was also true for poor performance on the identification subscore only. Based on the findings from this cohort, sample sizes for a hypothetical neuroprotection trial in RBD with conversion to a Lewy body disorders as an endpoint could be reduced by 74–80% for a 5-year trial if idiopathic RBD patients were pretested for baseline olfactory dysfunction. For example, a total of 760 patients with idiopathic RBD versus 188 patients with idiopathic RBD and olfactory dysfunction would be required to have an 80% chance to detect a 30% decrease in the primary outcome measure of conversion to a Lewy body disease [58]. Similar data were also reported by Postuma et al. who found that by excluding idiopathic RBD subjects \u003c55 years of age or using antidepressants reduced estimated sample sizes for 3-year neuroprotection trials with the same outcome measure by ≥25% when further pretesting for olfactory dysfunction, impaired colour vision, or subtle motor impairment and by ≥40% when using combinations of these markers [14]."}

{"project":"2_test","denotations":[{"id":"26485429-3505730-64047455","span":{"begin":166,"end":168},"obj":"3505730"},{"id":"26485429-16632313-64047456","span":{"begin":363,"end":365},"obj":"16632313"},{"id":"26485429-26208108-64047457","span":{"begin":578,"end":580},"obj":"26208108"},{"id":"26485429-23562390-64047458","span":{"begin":1106,"end":1108},"obj":"23562390"},{"id":"26485429-25767079-64047459","span":{"begin":1393,"end":1395},"obj":"25767079"},{"id":"26485429-25767079-64047460","span":{"begin":1959,"end":1961},"obj":"25767079"},{"id":"26485429-23562390-64047461","span":{"begin":2792,"end":2794},"obj":"23562390"},{"id":"26485429-25609758-64047462","span":{"begin":3029,"end":3031},"obj":"25609758"},{"id":"26485429-25609758-64047463","span":{"begin":3885,"end":3887},"obj":"25609758"},{"id":"26485429-25681454-64047464","span":{"begin":4293,"end":4295},"obj":"25681454"}],"text":"REM-sleep behavior disorder (RBD)\nRBD is a parasomnia clinically characterized by dream-enacting behaviours related to loss of physiological atonia during REM-sleep [59]. The prevalence of idiopathic RBD in the population is not well defined as definite diagnosis requires polysomnography. A commonly cited figure of 0.4% , however, may well be an underestimate [60]. Indeed, when using two validated screening questionnaires in an elderly population-based sample of 476 subjects, we recently found a prevalence of probable RBD of 5–8% in a Caucasian population aged \u003e60 years [61]. In this particular cross sectional study, probable RBD was associated with multiple other nonmotor markers of PD, while polysomnography was not available. Idiopathic RBD is increasingly recognized as a harbinger of neurodegenerative diseases, including not only PD but also other synucleinopathies like DLB or MSA. Several follow-up studies have found that the majority of subjects with idiopathic RBD (\u003e80%) will convert into one of these disorders –most commonly PD or DLB - with extended follow-up over decades [15, 54, 62]. Two recent prospective cohort studies have further substantiated these observations. Postuma and colleagues collected follow-up data in a multicentre sample of 305 patients with idiopathic RBD over up to 6 years and found an overall conversion to neurodegenerative diseases of 33% [63], which was time-dependent at 15% after 2 years, 25% after 3 years, and 41% after 5 years. Conversion to PD or DLB was common (42% and 50% , respectively), while only 8% converted to MSA. Idiopathic RBD patient who converted over the observational period were older, more likely to report a family history of dementia, and more frequently endorsed autonomic and/or motor symptoms on questionnaires compared to those who remained disease free, whereas many baseline characteristics including caffeine and nicotine exposure were not different between these groups [63]. With the aid of thorough testing batteries, conversion from RBD to PD or PD Dementia/DLB appears to be more predictable. One recent prospective study in 89 idiopathic RBD patients found that smell identification loss (hazard ratio (HR) 2.8), abnormal colour vision (HR, 3.1), and subtle motor impairment (HR, 3.9), as well as advanced age (HR, 1.1) and non-use of anti-depressants (HR, 3.5) was associated with conversion to one of these synucleinopathies (including MSA) over the 7.5 year observational period.\nTaken together, current evidence shows that RBD is the most specific among the different risk factors for PD (see Table 2) and RBD cohorts seem obvious candidates for future disease-prevention studies for PD. However, the median latency to conversion into clinically defined PD can be as long as 12 to 14 years [15, 54], seriously limiting the feasibility of such trials. Therefore, we recently investigated whether olfactory impairment can predict early conversion to PD or PDD/DLB among 35 idiopathic RBD patients prospectively followed over 5 years [58]. Indeed, abnormal baseline performance on the multidimensional SniffinSticks test assessing odour identification, odour discrimination, and olfactory threshold predicted conversion to a Lewy body disorder with an accuracy of 82.4% , and this was also true for poor performance on the identification subscore only. Based on the findings from this cohort, sample sizes for a hypothetical neuroprotection trial in RBD with conversion to a Lewy body disorders as an endpoint could be reduced by 74–80% for a 5-year trial if idiopathic RBD patients were pretested for baseline olfactory dysfunction. For example, a total of 760 patients with idiopathic RBD versus 188 patients with idiopathic RBD and olfactory dysfunction would be required to have an 80% chance to detect a 30% decrease in the primary outcome measure of conversion to a Lewy body disease [58]. Similar data were also reported by Postuma et al. who found that by excluding idiopathic RBD subjects \u003c55 years of age or using antidepressants reduced estimated sample sizes for 3-year neuroprotection trials with the same outcome measure by ≥25% when further pretesting for olfactory dysfunction, impaired colour vision, or subtle motor impairment and by ≥40% when using combinations of these markers [14]."}