Mild cognitive impairment in rapid eye movement sleep behavior disorder and Parkinson's disease

Centre d'étude du Sommeil et des Rythmes Biologiques, Hôpital du Sacré-Coeur de Montréal, Montréal, Québec, Canada.
Annals of Neurology (Impact Factor: 9.98). 07/2009; 66(1):39-47. DOI: 10.1002/ana.21680
Source: PubMed


To investigate the frequency and subtypes of mild cognitive impairment (MCI) in idiopathic rapid eye movement sleep behavior disorder (RBD) and Parkinson's disease (PD) in association with RBD.
One hundred and twelve subjects without dementia or major depression including 32 idiopathic RBD patients, 22 PD patients with polysomnography-confirmed RBD, 18 PD patients without RBD, and 40 healthy control subjects, underwent a comprehensive neuropsychological evaluation. We compared the proportion of patients with MCI between groups using standard diagnostic criteria.
MCI was found in 50% of idiopathic RBD patients and 73% of PD patients with RBD. In contrast, only 11% of PD patients without RBD and 8% of control subjects had MCI. The presence of MCI was significantly greater in idiopathic RBD patients and PD patients with RBD than in PD patients without RBD and control subjects. PD patients with RBD also performed worse than idiopathic RBD patients on neuropsychological tests assessing visuoconstructional and visuoperceptual abilities.
In both its association with PD and its idiopathic form, RBD is an important risk factor for MCI. Except for visuoconstructional and visuoperceptual problems, RBD may be an important determinant of cognitive impairment in PD. Ann Neurol 2009;66:39-47.

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    • "This finding was even more pronounced in some patients with RBD with scores below the norm from several cognitive tests for age, sex and education level. In addition, patients with RBD usually have a lower cognitive performance compared controls, independent of the groups being compared (i.e., idiopathic RBD vs. control group or Parkinson’s disease with vs. without RBD groups) [25]. Eventually, we serendipitously tested two patients with Lewy body dementia and RBD after sleep. "
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    ABSTRACT: To determine if sleep talkers with REM sleep behavior disorder (RBD) would utter during REM sleep sentences learned before sleep, and to evaluate their verbal memory consolidation during sleep. Eighteen patients with RBD and 10 controls performed two verbal memory tasks (16 words from the Free and Cued Selective Reminding Test and a 220-263 word long modified Story Recall Test) in the evening, followed by nocturnal video-polysomnography and morning recall (night-time consolidation). In 9 patients with RBD, daytime consolidation (morning learning/recall, evening recall) was also evaluated with the modified Story Recall Test in a cross-over order. Two RBD patients with dementia were studied separately. Sleep talking was recorded using video-polysomnography, and the utterances were compared to the studied texts by two external judges. Sleep-related verbal memory consolidation was maintained in patients with RBD (+24±36% words) as in controls (+9±18%, p=0.3). The two demented patients with RBD also exhibited excellent nighttime consolidation. The post-sleep performance was unrelated to the sleep measures (including continuity, stages, fragmentation and apnea-hypopnea index). Daytime consolidation (-9±19%) was worse than night-time consolidation (+29±45%, p=0.03) in the subgroup of 9 patients with RBD. Eleven patients with RBD spoke during REM sleep and pronounced a median of 20 words, which represented 0.0003% of sleep with spoken language. A single patient uttered a sentence that was judged to be semantically (but not literally) related to the text learned before sleep. Verbal declarative memory normally consolidates during sleep in patients with RBD. The incorporation of learned material within REM sleep-associated sleep talking in one patient (unbeknownst to himself) at the semantic level suggests a replay at a highly cognitive creative level.
    PLoS ONE 12/2013; 8(12):e83352. DOI:10.1371/journal.pone.0083352 · 3.23 Impact Factor
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    • "Moreover, the absence of these associations in the controls suggests that the associations between EEG measures and cognitive performance found in our study are specific to iRBD patients. Poor performance on the Trail Making Test Part B and the Block Design subtest has been reported in DLB and PD with cognitive impairment [6] [29] [30]. This observation suggests that both EEG slowing and impaired performance on these tasks could be early manifestations of cognitive decline in iRBD patients. "
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    ABSTRACT: Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a well-documented risk factor for synucleinopathies such as Parkinson disease (PD) and dementia with Lewy bodies (DLB). Moreover, approximately 50% of iRBD patients have mild cognitive impairment (MCI). The purpose of our study was to investigate waking electroencephalogram (EEG) abnormalities specific to iRBD patients with MCI. Forty-two polysomnographically confirmed iRBD patients, including 23 iRBD [+]MCI patients 19 patients without MCI (iRBD [-]MCI), and 37 healthy subjects participated in the study. All participants underwent a complete neuropsychologic assessment for MCI diagnosis and a waking quantitative EEG recording. iRBD [+]MCI patients had a higher slow-to-fast frequency ratio than iRBD [-]MCI patients and controls in the parietal, temporal, and occipital regions. iRBD [+]MCI patients also had higher relative θ power in the parietal, temporal, and occipital regions and lower relative α power in the occipital region compared to iRBD [-]MCI patients and controls. Moreover, iRBD [+]MCI patients had higher relative θ power in the frontal and central areas and lower relative β power in the central, parietal, and temporal regions compared to controls. The dominant occipital frequency also was slower in iRBD [+]MCI patients compared to controls. No between-group differences were observed between iRBD [-]MCI patients and controls. In iRBD patients, only those with concomitant MCI showed waking EEG slowing in the posterior cortical regions, providing a potential marker for an increased risk for developing DLB or PD.
    Sleep Medicine 09/2013; 14(11). DOI:10.1016/j.sleep.2013.06.013 · 3.15 Impact Factor
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    • "Criteria should be developed for how iRBD patients are tested and how the results can influence entry into the study. (F) RBD patients with mild cognitive impairment [34] [35] [36]. This inclusion is in line with the previous inclusion of RBD patients with soft neurologic dysfunction. "
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    ABSTRACT: We aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD) and related neurodegeneration in RBD. The consensus statement was generated during the fourth IRBD-SG symposium in Marburg, Germany in 2011. The IRBD-SG identified essential methodologic components for a randomized trial in RBD, including potential screening and diagnostic criteria, inclusion and exclusion criteria, primary and secondary outcomes for symptomatic therapy trials (particularly for melatonin and clonazepam), and potential primary and secondary outcomes for eventual trials with disease-modifying and neuroprotective agents. The latter trials are considered urgent, given the high conversion rate from idiopathic RBD (iRBD) to Parkinsonian disorders (i.e., PD, dementia with Lewy bodies [DLB], multiple system atrophy [MSA]). Six inclusion criteria were identified for symptomatic therapy and neuroprotective trials: (1) diagnosis of RBD needs to satisfy the International Classification of Sleep Disorders, second edition, (ICSD-2) criteria; (2) minimum frequency of RBD episodes should preferably be ⩾2 times weekly to allow for assessment of change; (3) if the PD-RBD target population is included, it should be in the early stages of PD defined as Hoehn and Yahr stages 1-3 in Off (untreated); (4) iRBD patients with soft neurologic dysfunction and with operational criteria established by the consensus of study investigators; (5) patients with mild cognitive impairment (MCI); and (6) optimally treated comorbid OSA. Twenty-four exclusion criteria were identified. The primary outcome measure for RBD treatment trials was determined to be the Clinical Global Impression (CGI) efficacy index, consisting of a four-point scale with a four-point side-effect scale. Assessment of video-polysomnographic (vPSG) changes holds promise but is costly and needs further elaboration. Secondary outcome measures include sleep diaries; sleepiness scales; PD sleep scale 2 (PDSS-2); serial motor examinations; cognitive indices; mood and anxiety indices; assessment of frequency of falls, gait impairment, and apathy; fatigue severity scale; and actigraphy and customized bed alarm systems. Consensus also was established for evaluating the clinical and vPSG aspects of RBD. End points for neuroprotective trials in RBD, taking lessons from research in PD, should be focused on the ultimate goal of determining the performance of disease-modifying agents. To date no compound with convincing evidence of disease-modifying or neuroprotective efficacy has been identified in PD. Nevertheless, iRBD patients are considered ideal candidates for neuroprotective studies. The IRBD-SG provides an important platform for developing multinational collaborative studies on RBD such as on environmental risk factors for iRBD, as recently reported in a peer-reviewed journal article, and on controlled active treatment studies for symptomatic and neuroprotective therapy that emerged during the 2011 consensus conference in Marburg, Germany, as described in our report.
    Sleep Medicine 07/2013; 15(1). DOI:10.1016/j.sleep.2013.02.016 · 3.15 Impact Factor
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