Anne Décary

REM SLEEP BEHAVIOR DISORDER PREDICTS COGNITIVE IMPAIRMENT IN PARKINSON DISEASE WITHOUT DEMENTIA

Objective: To assess the relationship between the presence of REM sleep behavior disorder (RBD) and the cognitive profile of nondemented patients with Parkinson disease (PD). Background: Cognitive impairment is an important nonmotor symptom in PD. Waking EEG slowing in nondemented PD has been related to the presence of RBD, a parasomnia affecting brainstem structures and frequently reported in PD. For this reason, RBD may be associated with cognitive impairment in PD. Methods: Thirty-four patients with PD (18 patients with polysomnographic-confirmed RBD and 16 patients without RBD) and 25 healthy control subjects matched for age and educational level underwent sleep laboratory recordings and a comprehensive neuropsychological assessment. Results: Patients with PD and concomitant RBD showed significantly poorer performance on standardized tests measuring episodic verbal memory, executive functions, as well as visuospatial and visuoperceptual processing compared to both patients with PD without RBD and control subjects. Patients with PD without RBD had no detectable cognitive impairment compared to controls. Conclusions: This study shows that cognitive impairment in nondemented patients with Parkinson disease (PD) is closely related to the presence of REM sleep behavior disorder, a sleep disturbance that was not controlled for in previous studies assessing cognitive deficits in PD. GLOSSARY: BDI-II = Beck-II Depression Inventory; DLB = dementia with Lewy bodies; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders; EOG = electro-oculograms; ICSD = International Classification of Sleep Disorders; MMSE = Mini-Mental State Examination; PD = Parkinson disease; PD-NRBD = patients with PD without RBD; PD-RBD = patients with concomitant RBD; RAVLT = Rey Auditory Verbal Learning Test; RBD = REM sleep behavior disorder; UPDRS = Unified Parkinsons Disease Rating Scale.

Slowing of electroencephalogram in rapid eye movement sleep behavior disorder.

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by a loss of atonia and an increase in phasic muscle activity during REM sleep, leading to complex nocturnal motor behaviors. Brainstem structures responsible for the pathogenesis of RBD are also implicated in cortical activation. To verify the hypothesis that electroencephalogram (EEG) activation will be impaired in RBD, we performed quantitative analyses of waking and REM sleep EEG in 15 idiopathic RBD patients and 15 age‐ and gender‐matched healthy subjects. During wakefulness, RBD patients showed a considerably higher θ power in frontal, temporal, and occipital regions with a lower β power in the occipital region. The dominant occipital frequency was significantly lower in RBD. During REM sleep, β power in the occipital region was lower in RBD. This study shows for the first time an impaired cortical activation during both wakefulness and REM sleep in idiopathic RBD, despite an absence of changes on sleep architecture compared with controls. EEG slowing in these patients may represent an early sign of central nervous system dysfunction, perhaps paralleled by subclinical cognitive deficits. The topographical distribution of EEG slowing and possible pathophysiological mechanisms are discussed in light of the known association between RBD and neurodegenerative disorders. Ann Neurol 2003;53:774–780

Executive dysfunction and memory impairment in idiopathic REM sleep behavior disorder

Background: Idiopathic REM sleep behavior disorder (iRBD) might be a stage in the development of neurodegenerative disorders, especially Parkinson disease and dementia with Lewy bodies. Recent studies showing a slowing of waking EEG in iRBD suggest that iRBD is associated with cognitive impairment. Objective: To compare patients with iRBD on measures of cognitive function and quantitative waking EEG. Methods: Fourteen patients with iRBD and 14 healthy control subjects matched for age and educational level were studied. Subjects underwent an extensive neuropsychological evaluation and waking EEG recordings. Results: Compared to controls, patients with iRBD showed a lower performance on neuropsychological tests measuring attention, executive functions, and verbal memory. Moreover, patients with iRBD showed EEG slowing (higher delta and theta power) during wakefulness in all brain areas compared to controls. However, no correlation was found between performance on cognitive tests and quantitative waking EEG in patients with iRBD. Conclusion: This study shows a co-occurrence of impaired cognitive profile and waking EEG slowing in patients with idiopathic REM sleep behavior disorder similar to that observed in early stages of some synucleinopathies.

Assessing whole brain perfusion changes in patients with REM sleep behavior disorder.

Objective: To investigate the regional cerebral perfusion in patients with idiopathic REM behavior disorder (RBD) in order to establish the topography of networks involved. Methods: We performed cerebral blood flow evaluation using 99mTc-Ethylene Cysteinate Dimer (ECD) SPECT on eight patients with polysomnographically confirmed RBD and nine age-matched controls. Comparisons were made using SPM2. Results: We found increased perfusion in the pons and putamen bilaterally and in the right hippocampus. In addition, we observed a decreased perfusion in frontal (Brodmann area [BA] 4, 6, 10, 43, 44, 47 bilaterally and left BA 9, 46) and temporo-parietal (BA 13, 22, 43 bilaterally and left BA 7, 19, 20, 21, 39, 40, 41, 42) cortices. Conclusion: Perfusional abnormalities in patients with REM behavior disorder were located in the brainstem, striatum, and cortex. These abnormalities are consistent with the anatomic metabolic profile of Parkinson disease.

Association between waking EEG slowing and REM sleep behavior disorder in PD without dementia

Objective: To compare nondemented patients with Parkinson’s disease (PD) with and without REM sleep behavior disorder (RBD) to healthy controls on quantitative EEG characteristics for both wakefulness and REM sleep. Methods: Fifteen patients with PD (7 patients with polysomnographic-confirmed RBD [PD-RBD] and 8 patients without RBD [PD-NRBD]) and 15 healthy control subjects were studied. Each subject underwent a quantitative EEG analysis of both wakefulness and REM sleep. Results: During wakefulness, patients with PD-RBD showed a higher theta power in frontal, parietal, temporal, and occipital regions in comparison to patients with PD-NRBD and control subjects. Moreover, a slowing of the dominant occipital frequency was observed only in patients with PD-RBD (p < 0.02). Patients with PD-NRBD did not present any slowing of the EEG. No between-group difference in quantitative REM sleep EEG was observed. Conclusions: This study demonstrates that the EEG slowing reported during wakefulness in nondemented patients with PD is strongly related to the presence of RBD.

Slow-wave sleep and delta power in rapid eye movement sleep behavior disorder

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by the loss of normal muscle atonia during REM sleep, leading to an increase of phasic muscle activity and complex motor behaviors during the night. There is some evidence that RBD patients have more of slow‐wave sleep (SWS) than healthy elderly subjects. No study has looked at quantitative electroencephalogram analysis during non‐REM sleep in either primary or secondary RBD. The aim of this study was to assess the increase of SWS and to analyze different electroencephalographic frequency ranges during non‐REM sleep in 28 idiopathic RBD patients compared with 28 age‐ and sex‐matched healthy volunteers. Idiopathic RBD patients spent more time in SWS (men: 1.4%; women: 5.9%) than control subjects (men: 0.4%; women: 0.6%; p = 0.004). Spectral analyses demonstrated that idiopathic RBD patients had increased all‐night δ power in comparison with control subjects (p = 002). This study shows an increase of SWS and power in the δ band during non‐REM sleep in idiopathic RBD patients compared with control subjects. Results are discussed about the possible nigrostriatal dopaminergic impairment in RBD patients and the association between RBD and neurodegenerative disorders. Ann Neurol 2005;57:277–282

Deficits in involuntary attention switching in obstructive sleep apnea syndrome

Cognitive functions are altered in patients with obstructive sleep apnea syndrome (OSAS) and it has been proposed that vigilance and attentional deficits play a pivotal role in all aspects of these deficits. One way to assess attentional system integrity is the study of event-related-potentials (ERP), but only a few ERP studies have been conducted in patients with OSAS. The aim of the study was to use ERP to further assess attentional impairments in these patients. Thirteen OSAS patients and 13 age-matched controls underwent a night of polysomnographic recording. Each subject was also tested with an ERP paradigm where standard (95%, 1000Hz), high deviant (2.5%, 1250Hz) and low deviant (2.5%, 1050Hz) tones were presented. Subjects were asked to ignore the stimuli and read during the task. Mismatch negativity (MMN) and P3a amplitudes and latencies were measured. No between-group difference was observed for sleep stages, except a lower percentage of rapid eye movement (REM) sleep in patients with OSAS (p<0.01). Moreover, the OSAS group showed a higher micro-arousal index and more sleep transitions than the control group (p<0.05). A significant group effect was found for the amplitude of the P3a component (p<0.05) that was lower in patients with OSAS for both high and low deviant tones. No between-group difference was found for the MMN and the P3a latencies. In conclusion, patients with OSAS have specific alterations of the P3a component that reflects involuntary attention switching, but automatic auditory processing assessed by MMN appears to be preserved.

Does age worsen EEG slowing and attention deficits in obstructive sleep apnea syndrome

OBJECTIVE The aim of this study was to determine whether EEG slowing is more pronounced in older than younger OSAS patients and to verify whether this cortical slowing is correlated to daytime performance, respiratory perturbation and sleep fragmentation. METHODS Twelve young OSAS patients (mean age 38.2+/-2.0 y) and 13 older OSAS patients (mean age 62.2+/-1.9 y) along with 13 young controls (mean age 35.8+/-2.0 y) and 14 older controls (mean age 60.2+/-2.0 y) underwent a polysomnographic evaluation followed by a waking EEG recording. As a global index of cortical slowing, a ratio of slow-to-fast frequencies was calculated in all cortical regions. Daytime performance was assessed using the four choice reaction time test. RESULTS Differences in waking EEG and in daytime performance were analyzed by ANOVAs with Group and Age as factors. Waking EEG did not yield a Group by Age interaction. OSAS patients had higher ratios across all regions than controls. Similarly, daytime performance revealed no Group by Age interaction. However, OSAS patients showed more lapses than controls and older subjects were slower than younger subjects. CONCLUSIONS Our results indicate that age does not interact with OSAS to worsen the severity of cortical slowing, but age can add to the OSAS effect to worsen daytime performance deficits in OSAS patients. SIGNIFICANCE The daytime performance deficits observed particularly in elderly OSAS patients warrant a careful clinical assessment of these patients to prevent accidents and injuries.