Objective
To assess whether risk factors for Parkinson disease and dementia with Lewy bodies increase rate of defined neurodegenerative disease in idiopathic rapid eye movement (REM) sleep behavior ...disorder (RBD).
Methods
Twelve centers administered a detailed questionnaire assessing risk factors for neurodegenerative synucleinopathy to patients with idiopathic RBD. Variables included demographics, lifestyle factors, pesticide exposures, occupation, comorbid conditions, medication use, family history, and autonomic/motor symptoms. After 4 years of follow‐up, patients were assessed for dementia or parkinsonism. Disease risk was assessed with Kaplan–Meier analysis, and epidemiologic variables were compared between convertors and those still idiopathic using logistic regression.
Results
Of 305 patients, follow‐up information was available for 279, of whom 93 (33.3%) developed defined neurodegenerative disease. Disease risk was 25% at 3 years and 41% after 5 years. Patients who converted were older (difference = 4.5 years, p < 0.001), with similar sex distribution. Neither caffeine, smoking, nor alcohol exposure predicted conversion. Although occupation was similar between groups, those who converted had a lower likelihood of pesticide exposure (occupational insecticide = 2.3% vs 9.0%). Convertors were more likely to report family history of dementia (odds ratio OR = 2.09), without significant differences in Parkinson disease or sleep disorders. Medication exposures and medical history were similar between groups. Autonomic and motor symptoms were more common among those who converted. Risk factors for primary dementia and parkinsonism were generally similar, except for a notably higher clonazepam use in dementia convertors (OR = 2.6).
Interpretation
Patients with idiopathic RBD are at very high risk of neurodegenerative synucleinopathy. Risk factor profiles between convertors and nonconvertors have both important commonalities and differences. Ann Neurol 2015;77:830–839
Objective
This study was undertaken to follow up predictive factors for α‐synuclein–related neurodegenerative diseases in a multicenter cohort of idiopathic/isolated rapid eye movement sleep behavior ...disorder (iRBD).
Methods
Patients with iRBD from 12 centers underwent a detailed assessment for potential environmental and lifestyle risk factors via a standardized questionnaire at baseline. Patients were then prospectively followed and received assessments for parkinsonism or dementia during follow‐up. The cumulative incidence of parkinsonism or dementia was estimated with competing risk analysis. Cox regression analyses were used to evaluate the predictive value of environmental/lifestyle factors over a follow‐up period of 11 years, adjusting for age, sex, and center.
Results
Of 319 patients who were free of parkinsonism or dementia, 281 provided follow‐up information. After a mean follow‐up of 5.8 years, 130 (46.3%) patients developed neurodegenerative disease. The overall phenoconversion rate was 24.2% after 3 years, 44.8% after 6 years, and 67.5% after 10 years. Patients with older age (adjusted hazard ratio aHR = 1.05) and nitrate derivative use (aHR = 2.18) were more likely to phenoconvert, whereas prior pesticide exposure (aHR = 0.21–0.64), rural living (aHR = 0.53), lipid‐lowering medication use (aHR = 0.59), and respiratory medication use (aHR = 0.36) were associated with lower phenoconversion risk. Risk factors for those converting to primary dementia and parkinsonism were generally similar, with dementia‐first converters having lower coffee intake and beta‐blocker intake, and higher occurrence of family history of dementia.
Interpretation
Our findings elucidate the predictive values of environmental factors and comorbid conditions in identifying RBD patients at higher risk of phenoconversion. ANN NEUROL 2022;91:404–416
Growing evidence suggests that sleep plays a key role in regulating emotions. Rapid eye movements (REMs) in REM sleep could be associated with dreams emotions, but supporting evidence is indirect. To ...highlight this association, we studied the REM sleep during video-polysomnography of 20 subjects with REM sleep behaviour disorder (RBD), a model of enacted dreams offering direct access to the emotional content of the sleeper (face expression, speeches, behaviour). Video and the electro-oculography recordings were divided into 3 s time intervals and classified as non-behavioural, or behavioural (neutral, positive or negative emotions), and as containing no eye movements (EMs), slow eye movements (SEMs) or REMs (isolated or bursts). Compared to the absence of EMs, neutral behaviours successively increased in the presence of SEMs (odd ratio, OR = 1.4), then isolated REMs (OR = 2.8) and then REM bursts (OR = 4.6). Positive behaviours increased with SEMs (OR = 2.8) but did not increase further with isolated REMs (OR = 2.8) and REM bursts (OR = 3). Negative behaviours were absent with SEMs, increased with isolated REMs (OR = 2.6) and further with REM bursts (OR = 10.1). These results support an association between REMs and SEMs, and dream emotions.
In Parkinson's disease, there is a progressive reduction in striatal dopaminergic function, and loss of neuromelanin-containing dopaminergic neurons and increased iron deposition in the substantia ...nigra. We tested the hypothesis of a relationship between impairment of the dopaminergic system and changes in the iron metabolism. Based on imaging data of patients with prodromal and early clinical Parkinson's disease, we assessed the spatiotemporal ordering of such changes and relationships in the sensorimotor, associative and limbic territories of the nigrostriatal system. Patients with Parkinson's disease (disease duration < 4 years) or idiopathic REM sleep behaviour disorder (a prodromal form of Parkinson's disease) and healthy controls underwent longitudinal examination (baseline and 2-year follow-up). Neuromelanin and iron sensitive MRI and dopamine transporter single-photon emission tomography were performed to assess nigrostriatal levels of neuromelanin, iron, and dopamine. For all three functional territories of the nigrostriatal system, in the clinically most and least affected hemispheres separately, the following was performed: cross-sectional and longitudinal intergroup difference analysis of striatal dopamine and iron, and nigral neuromelanin and iron; in Parkinson's disease patients, exponential fitting analysis to assess the duration of the prodromal phase and the temporal ordering of changes in dopamine, neuromelanin or iron relative to controls; and voxel-wise correlation analysis to investigate concomitant spatial changes in dopamine-iron, dopamine-neuromelanin and neuromelanin-iron in the substantia nigra pars compacta. The temporal ordering of dopaminergic changes followed the known spatial pattern of progression involving first the sensorimotor, then the associative and limbic striatal and nigral regions. Striatal dopaminergic denervation occurred first followed by abnormal iron metabolism and finally neuromelanin changes in the substantia nigra pars compacta, which followed the same spatial and temporal gradient observed in the striatum but shifted in time. In conclusion, dopaminergic striatal dysfunction and cell loss in the substantia nigra pars compacta are interrelated with increased nigral iron content.
Summary
Patients with idiopathic hypersomnia never feel fully alert despite a normal or long sleep night. The spectrum of the symptoms is insufficiently studied. We interviewed 62 consecutive ...patients with idiopathic hypersomnia (with a mean sleep latency lower than 8 min or a sleep time longer than 11 h) and 50 healthy controls using a questionnaire on sleep, awakening, sleepiness, alertness and cognitive, psychological and functional problems during daily life conditions. Patients slept 3 h more on weekends, holidays and in the sleep unit than on working days. In the morning, the patients needed somebody to wake them, or to be stressed, while routine, light, alarm clocks and motivation were inefficient. Three‐quarters of the patients did not feel refreshed after short naps. During the daytime, their alertness was modulated by the same external conditions as controls, but they felt more sedated in darkness, in a quiet environment, when listening to music or conversation. Being hyperactive helped them more than controls to resist sleepiness. They were more frequently evening‐type and more alert in the evening than in the morning. The patients were able to focus only for 1 h (versus 4 h in the controls). They complained of attention and memory deficit. Half of them had problems regulating their body temperature and were near‐sighted. Mental fatigability, dependence on other people for awakening them, and a reduced benefit from usually alerting conditions (except being hyperactive or stressed) seem to be more specific of the daily problems of patients with idiopathic hypersomnia than daytime sleepiness.