Publications by authors named "Nadia Gosselin"

84 Publications

Sleeping at the switch.

Elife 2021 08 27;10. Epub 2021 Aug 27.

Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, Montreal, Canada.

Sleep slow waves are studied for their role in brain plasticity, homeostatic regulation, and their changes during aging. Here, we address the possibility that two types of slow waves co-exist in humans. Thirty young and 29 older adults underwent a night of polysomnographic recordings. Using the slow waves with a slow transition (slow switchers) and those with a fast transition (fast switchers) were discovered. Slow switchers had a high electroencephalography (EEG) connectivity along their depolarization transition while fast switchers had a lower connectivity dynamics and dissipated faster during the night. Aging was associated with lower temporal dissipation of sleep pressure in slow and fast switchers and lower EEG connectivity at the microscale of the oscillations, suggesting a decreased flexibility in the connectivity network of older individuals. Our findings show that two different types of slow waves with possible distinct underlying functions coexist in the slow wave spectrum.
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http://dx.doi.org/10.7554/eLife.64337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452310PMC
August 2021

Obstructive Sleep Apnea and Cognitive Decline: A Review of Potential Vulnerability and Protective Factors.

Brain Sci 2021 May 27;11(6). Epub 2021 May 27.

Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, Recherche CIUSSS NIM, Montreal, QC H4J 1C5, Canada.

Around 40% of dementia risk is attributable to modifiable risk factors such as physical inactivity, hypertension, diabetes and obesity. Recently, sleep disorders, including obstructive sleep apnea (OSA), have also been considered among these factors. However, despite several epidemiological studies investigating the link between OSA and cognitive decline, there is still no consensus on whether OSA increases the risk of dementia or not. Part of the heterogeneity observed in previous studies might be related to some individual characteristics that modulate the association between OSA and cognitive decline. In this narrative review, we present these individual characteristics, namely, age, sex, menopause, obesity, diabetes mellitus, hypertension, cardiovascular diseases, smoking, excessive alcohol consumption, depression, air pollution, allele, physical activity, and cognitive reserve. To date, large cohort studies of OSA and cognitive decline tended to statistically control for the effects of these variables, but whether they interact with OSA to predict cognitive decline remains to be elucidated. Being able to better predict who is at risk of cognitive decline when they have OSA would improve clinical management and treatment decisions, particularly when patients present relatively mild OSA.
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http://dx.doi.org/10.3390/brainsci11060706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226698PMC
May 2021

Longitudinal changes in regional cerebral blood flow in late middle-aged and older adults with treated and untreated obstructive sleep apnea.

Hum Brain Mapp 2021 Aug 3;42(11):3429-3439. Epub 2021 May 3.

Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, Centre Intégré Universitaire de Santé et de Services Sociaux du Nord de l'Île-de-Montréal, Montreal, Quebec, Canada.

Obstructive sleep apnea (OSA) is associated with abnormal cerebral perfusion at wakefulness, but whether these anomalies evolve over time is unknown. Here, we examined longitudinal changes in regional cerebral blood flow (rCBF) distribution in late middle-aged and older adults with treated or untreated OSA. Twelve controls (64.8 ± 8.0 years) and 23 participants with newly diagnosed OSA (67.8 ± 6.2 years) were evaluated with polysomnography and cerebral Tc-HMPAO single-photon emission computed tomography during wakeful rest. OSA participants were referred to a sleep apnea clinic and 13 of them decided to start continuous positive airway pressure (CPAP). Participants were tested again after 18 months. Voxel-based analysis and extracted relative rCBF values were used to assess longitudinal changes. Untreated OSA participants showed decreased relative rCBF in the left hippocampus and the right parahippocampal gyrus over time, while treated participants showed trends for increased relative rCBF in the left hippocampus and the right parahippocampal gyrus. No changes were found over time in controls. Untreated OSA is associated with worsening relative rCBF in specific brain areas over time, while treated OSA shows the opposite. Considering that OSA possibly accelerates cognitive decline in older adults, CPAP treatment could help reduce risk for cognitive impairment.
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http://dx.doi.org/10.1002/hbm.25443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249886PMC
August 2021

Cerebral functional networks during sleep in young and older individuals.

Sci Rep 2021 03 1;11(1):4905. Epub 2021 Mar 1.

Functional Neuroimaging Unit, University of Montreal Geriatric Institute, 4565, Queen-Mary Road, Montreal, QC, H3W 1W5, Canada.

Even though sleep modification is a hallmark of the aging process, age-related changes in functional connectivity using functional Magnetic Resonance Imaging (fMRI) during sleep, remain unknown. Here, we combined electroencephalography and fMRI to examine functional connectivity differences between wakefulness and light sleep stages (N1 and N2 stages) in 16 young (23.1 ± 3.3y; 7 women), and 14 older individuals (59.6 ± 5.7y; 8 women). Results revealed extended, distributed (inter-between) and local (intra-within) decreases in network connectivity during sleep both in young and older individuals. However, compared to the young participants, older individuals showed lower decreases in connectivity or even increases in connectivity between thalamus/basal ganglia and several cerebral regions as well as between frontal regions of various networks. These findings reflect a reduced ability of the older brain to disconnect during sleep that may impede optimal disengagement for loss of responsiveness, enhanced lighter and fragmented sleep, and contribute to age effects on sleep-dependent brain plasticity.
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http://dx.doi.org/10.1038/s41598-021-84417-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921592PMC
March 2021

Obstructive Sleep Apnea and the Brain: a Focus on Gray and White Matter Structure.

Curr Neurol Neurosci Rep 2021 02 14;21(3):11. Epub 2021 Feb 14.

Center for Advanced Research in Sleep Medicine, Centre Intégré Universitaire de Santé et de Services Sociaux du Nord-de-l'Île-de-Montréal, 5400 boul. Gouin Ouest, local J-5135, Montréal, Québec, H4J 1C5, Canada.

Purpose Of Review: Obstructive sleep apnea is extremely prevalent in the elderly and may precipitate dementia. We review recent advances on gray and white matter structure in obstructive sleep apnea, the impact of treatment, and potential pathological and neurodegenerative processes underlying brain structural changes.

Recent Findings: Two opposite patterns are observed in neuroimaging studies of obstructive sleep apnea. One may indicate cellular damage (gray matter atrophy, higher white matter hyperintensity burden, lower white matter fractional anisotropy, higher water diffusivities), while the other (gray matter hypertrophy, restricted white matter diffusivities) may reflect transitory responses, such as intracellular edema, reactive gliosis or compensatory structural changes. Treating obstructive sleep apnea could partly reverse these structural changes. Structural alterations related to obstructive sleep apnea may follow a multi-determined biphasic pattern depending on numerous factors (e.g. severity, symptomatology, age) that could tip the scale toward neurodegeneration and need to be investigated by longitudinal studies.
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http://dx.doi.org/10.1007/s11910-021-01094-2DOI Listing
February 2021

Slow wave activity moderates the association between new learning and traumatic brain injury severity.

Sleep 2021 04;44(4)

Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, Centre de Recherche du CIUSSS NIM, Montreal, Quebec, Canada.

Study Objectives: Sleep-wake complaints and difficulties in making new learning are among the most persistent and challenging long-term sequelea following moderate to severe traumatic brain injury (TBI). Yet, it is unclear whether, and to what extent, sleep characteristics during the chronic stage of TBI contribute to sleep-wake and cognitive complaints. We aimed to characterize sleep architecture in chronic moderate to severe TBI adults and assess whether non-rapid eye movement slow wave activity (SWA) is associated to next day performance in episodic memory tasks according to TBI severity.

Methods: Forty-two moderate to severe TBI participants, 12-47 months post-injury, and 38 healthy controls were tested with one night of in-laboratory polysomnography, followed the next morning by questionnaires (sleep quality, fatigue, and sleepiness) and neuropsychological assessment. We used multiple regression analyses to assess the moderator effect of SWA power on TBI severity and next-day memory performance.

Results: We found that TBI participants reported worse sleep quality and fatigue, and had worse cognitive performance than controls. No between group differences were found on macro- and micro-architecture of sleep. However, SWA significantly interacted with TBI severity to explain next-day memory performance: higher SWA was more strongly associated to better memory performance in more severe TBI compared to milder TBI.

Conclusions: This study provides evidence that the injured brain is able to produce macro- and micro-architecture of sleep comparable to what is seen in healthy controls. However, with increasing TBI severity, lower non-rapid eye movement SWA power is associated with reduced ability to learn and memorise new information the following day.
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http://dx.doi.org/10.1093/sleep/zsaa242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033458PMC
April 2021

Sleep spindles are resilient to extensive white matter deterioration.

Brain Commun 2020 13;2(2):fcaa071. Epub 2020 Jun 13.

Research Center of the Centre Intégré Universitaire de Santé et de Services Sociaux du Nord de l'Île-de-Montréal, Montreal H4J 1C5, Canada.

Sleep spindles are an essential part of non-rapid eye movement sleep, notably involved in sleep consolidation, cognition, learning and memory. These oscillatory waves depend on an interaction loop between the thalamus and the cortex, which relies on a structural backbone of thalamo-cortical white matter tracts. It is still largely unknown if the brain can properly produce sleep spindles when it underwent extensive white matter deterioration in these tracts, and we hypothesized that it would affect sleep spindle generation and morphology. We tested this hypothesis with chronic moderate to severe traumatic brain injury ( = 23; 30.5 ± 11.1 years old; 17 m/6f), a unique human model of extensive white matter deterioration, and a healthy control group ( = 27; 30.3 ± 13.4 years old; 21m/6f). Sleep spindles were analysed on a full night of polysomnography over the frontal, central and parietal brain regions, and we measured their density, morphology and sigma-band power. White matter deterioration was quantified using diffusion-weighted MRI, with which we performed both whole-brain voxel-wise analysis (Tract-Based Spatial Statistics) and probabilistic tractography (with High Angular Resolution Diffusion Imaging) to target the thalamo-cortical tracts. Group differences were assessed for all variables and correlations were performed separately in each group, corrected for age and multiple comparisons. Surprisingly, although extensive white matter damage across the brain including all thalamo-cortical tracts was evident in the brain-injured group, sleep spindles remained completely undisrupted when compared to a healthy control group. In addition, almost all sleep spindle characteristics were not associated with the degree of white matter deterioration in the brain-injured group, except that more white matter deterioration correlated with lower spindle frequency over the frontal regions. This study highlights the resilience of sleep spindles to the deterioration of all white matter tracts critical to their existence, as they conserve normal density during non-rapid eye movement sleep with mostly unaltered morphology. We show that even with such a severe traumatic event, the brain has the ability to adapt or to withstand alterations in order to conserve normal sleep spindles.
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http://dx.doi.org/10.1093/braincomms/fcaa071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472897PMC
June 2020

Are age and sex effects on sleep slow waves only a matter of electroencephalogram amplitude?

Sleep 2021 03;44(3)

Center for Advanced Research in Sleep Medicine, CIUSSS-NÎM-Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada.

Aging is associated with reduced slow wave (SW) density (number SW/min in nonrapid-eye movement sleep) and amplitude. It has been proposed that an age-related decrease in SW density may be due to a reduction in electroencephalogram (EEG) amplitude instead of a decline in the capacity to generate SW. Here, we propose a data-driven approach to adapt SW amplitude criteria to age and sex. We predicted that the adapted criteria would reduce age and sex differences in SW density and SW characteristics but would not abolish them. A total of 284 healthy younger and older adults participated in one night of sleep EEG recording. We defined age- and sex-adapted SW criteria in a first cohort of younger (n = 97) and older (n = 110) individuals using a signal-to-noise ratio approach. We then used these age- and sex-specific criteria in an independent second cohort (n = 77, 38 younger and 39 older adults) to evaluate age and sex differences on SW density and SW characteristics. After adapting SW amplitude criteria, we showed maintenance of an age-related difference for SW density whereas the sex-related difference vanished. Indeed, older adults produced less SW compared with younger adults. Specifically, the adapted SW amplitude criteria increased the probability of occurrence of low amplitude SW (<80 µV) for older men especially. Our results thereby confirm an age-related decline in SW generation rather than an artifact in the detection amplitude criteria. As for the SW characteristics, the age- and sex-adapted criteria display reproducible effects across the two independent cohorts suggesting a more reliable inventory of the SW.
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http://dx.doi.org/10.1093/sleep/zsaa186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953219PMC
March 2021

Waking EEG functional connectivity in middle-aged and older adults with obstructive sleep apnea.

Sleep Med 2020 11 14;75:88-95. Epub 2020 Jun 14.

Center for Advanced Research in Sleep Medicine, CIUSSS du Nord de l'Île-de-Montréal, Hôpital du Sacré-Coeur de Montréal, 5400 Boulevard Gouin Ouest, Montréal, Québec, H4J 1C5, Canada; Département de Psychologie, Université de Montréal, Pavillon Marie-Victorin, C. P. 6128, Succursale Centre-ville, Montréal, Québec, H3C 3J7, Canada. Electronic address:

Objectives: The present study aimed at investigating changes in waking electroencephalography (EEG), most specifically regarding spectral power and functional connectivity, in middle-aged and older adults with obstructive sleep apnea (OSA). We also explored whether changes in spectral power or functional connectivity are associated with polysomnographic characteristics and/or neuropsychological performance.

Methods: In sum, 19 OSA subjects (apnea-hypopnea index ≥ 20, age: 63.6 ± 6.4) and 22 controls (apnea-hypopnea index ≤ 10, age: 63.6 ± 6.7) underwent a full night of in-laboratory polysomnography (PSG) followed by a waking EEG and a neuropsychological assessment. Waking EEG spectral power and imaginary coherence were compared between groups for all EEG frequency bands and scalp regions. Correlation analyses were performed between selected waking EEG variables, polysomnographic parameters and neuropsychological performance.

Results: No group difference was observed for EEG spectral power for any frequency band. Regarding the imaginary coherence, when compared to controls, OSA subjects showed decreased EEG connectivity between frontal and temporal regions in theta and alpha bands as well as increased connectivity between frontal and parietal regions in delta and beta 1 bands. In the OSA group, these changes in connectivity correlated with lower sleep efficiency, lower total sleep time and higher apnea-hypopnea index. No relationship was found with neuropsychological performance.

Conclusions: Contrary to spectral power, imaginary coherence was sensitive enough to detect changes in brain function in middle-aged and older subjects with OSA when compared to controls. Whether these changes in cerebral connectivity predict cognitive decline needs to be investigated longitudinally.
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http://dx.doi.org/10.1016/j.sleep.2020.06.008DOI Listing
November 2020

Changes in Regional Cerebral Perfusion Over Time in Idiopathic REM Sleep Behavior Disorder.

Mov Disord 2020 08 27;35(8):1475-1481. Epub 2020 May 27.

Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Cœur de Montréal, Centre intégré universitaire de santé et de services sociaux du Nord de l'île-de-Montréal, Montreal, Canada.

Background: Idiopathic rapid eye movement sleep behavior disorder is associated with increased risk of neurodegeneration, but the temporal evolution of regional perfusion, a marker of cerebral activity, has not been characterized. The objective of the current study was to study longitudinal regional perfusion in patients with idiopathic rapid eye movement sleep behavior disorder.

Methods: Thirty-seven patients and 23 controls underwent high-resolution single-photon emission computed tomography. After 17 months on average, scans were repeated for idiopathic rapid eye movement sleep behavior disorder patients. We compared regional cerebral blood flow between groups and over time.

Results: At baseline, patients showed lower relative regional perfusion in the anterior frontal and lateral parietotemporal cortex compared with controls. However, over time, patients showed an increase in relative regional perfusion in the anterior frontal, lateral parietal, and occipitotemporal cortex, reverting toward normal control levels.

Conclusions: Patients with idiopathic rapid eye movement sleep behavior disorder showed significant areas of relative regional hypoperfusion, which disappeared over time to finally return to average levels, suggesting possible developing compensation in areas affected by neurodegeneration. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28092DOI Listing
August 2020

Moderate to severe acute pain disturbs motor cortex intracortical inhibition and facilitation in orthopedic trauma patients: A TMS study.

PLoS One 2020 20;15(3):e0226452. Epub 2020 Mar 20.

Hôpital Sacré-Cœur de Montréal (HSCM), Montreal, QC, Canada.

Objective: Primary motor (M1) cortical excitability alterations are involved in the development and maintenance of chronic pain. Less is known about M1-cortical excitability implications in the acute phase of an orthopedic trauma. This study aims to assess acute M1-cortical excitability in patients with an isolated upper limb fracture (IULF) in relation to pain intensity.

Methods: Eighty-four (56 IULF patients <14 days post-trauma and 28 healthy controls). IULF patients were divided into two subgroups according to pain intensity (mild versus moderate to severe pain). A single transcranial magnetic stimulation (TMS) session was performed over M1 to compare groups on resting motor threshold (rMT), short-intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval cortical inhibition (LICI).

Results: Reduced SICI and ICF were found in IULF patients with moderate to severe pain, whereas mild pain was not associated with M1 alterations. Age, sex, and time since the accident had no influence on TMS measures.

Discussion: These findings show altered M1 in the context of acute moderate to severe pain, suggesting early signs of altered GABAergic inhibitory and glutamatergic facilitatory activities.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226452PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083311PMC
May 2020

Cerebral white matter diffusion properties and free-water with obstructive sleep apnea severity in older adults.

Hum Brain Mapp 2020 07 13;41(10):2686-2701. Epub 2020 Mar 13.

Research Centre, Hôpital du Sacré-Coeur de Montréal, Montréal, Québec, Canada.

Characterizing the effects of obstructive sleep apnea (OSA) on the aging brain could be key in our understanding of neurodegeneration in this population. Our objective was to assess white matter properties in newly diagnosed and untreated adults with mild to severe OSA. Sixty-five adults aged 55 to 85 were recruited and divided into three groups: control (apnea-hypopnea index ≤5/hr; n = 18; 65.2 ± 7.2 years old), mild (>5 to ≤15 hr; n = 27; 64.2 ± 5.3 years old) and moderate to severe OSA (>15/hr; n = 20; 65.2 ± 5.5 years old). Diffusion tensor imaging metrics (fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity, and mean diffusivity) were compared between groups with Tract-Based Spatial Statistics within the white matter skeleton created by the technique. Groups were also compared for white matter hyperintensities volume and the free-water (FW) fraction. Compared with controls, mild OSA participants showed widespread areas of lower diffusivity (p < .05 corrected) and lower FW fraction (p < .05). Participants with moderate to severe OSA showed lower AD in the corpus callosum compared with controls (p < .05 corrected). No between-group differences were observed for FA or white matter hyperintensities. Lower white matter diffusivity metrics is especially marked in mild OSA, suggesting that even the milder form may lead to detrimental outcomes. In moderate to severe OSA, competing pathological responses might have led to partial normalization of diffusion metrics.
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http://dx.doi.org/10.1002/hbm.24971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294053PMC
July 2020

Long-term discourse outcomes and their relationship to white matter damage in moderate to severe adulthood traumatic brain injury.

Brain Lang 2020 05 17;204:104769. Epub 2020 Feb 17.

Centre de recherche du Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal (Hôpital du Sacré-Coeur de Montréal), Montréal, Québec, Canada; Département de psychologie, Faculté des arts et Sciences, Université de Montréal, Montréal, Québec, Canada.

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http://dx.doi.org/10.1016/j.bandl.2020.104769DOI Listing
May 2020

Validity of actigraphy for nighttime sleep monitoring in hospitalized patients with traumatic injuries.

J Clin Sleep Med 2020 02 13;16(2):185-192. Epub 2020 Jan 13.

Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Cœur de Montréal, Montreal, Canada.

Study Objectives: Sleep-wake disturbances are frequent among patients hospitalized for traumatic injuries but remain poorly documented because of the lack of tools validated for hospitalized patients. This study aimed to validate actigraphy for nighttime sleep monitoring of hospitalized patients with severe traumatic injuries, using ambulatory polysomnography (PSG).

Methods: We tested 17 patients (30.4 ± 14.7 years, 16.6 ± 8.2 days postinjury) who had severe orthopedic injuries and/or spinal cord injury, with or without traumatic brain injury. When medically stable, patients wore an actigraph on a nonparalyzed arm and underwent ambulatory PSG at the bedside. Data were converted to 1-minute epochs. The following parameters were calculated for the nighttime period: total sleep time, total wake time, sleep efficiency, and number of awakenings. Epoch-by-epoch concordance between actigraphy and PSG was analyzed to derive sensitivity, specificity, and accuracy. PSG sleep parameters were compared to those obtained from four actigraphy scoring algorithms by Bland-Altman plots.

Results: Sensitivity to detect sleep was ≥ 92% and accuracy was > 85% for all four actigraphy algorithms used, whereas specificity varied from 48% to 60%. The low-activity wake threshold (20 activity counts per epoch) was most closely associated with PSG on all sleep parameters. This scoring algorithm also had the highest specificity (59.9%) and strong sensitivity (92.8%).

Conclusions: Actigraphy is valid for monitoring nighttime sleep and wakefulness in patients hospitalized with traumatic injuries, with sensitivity, specificity and accuracy comparable to actigraphic recordings in healthy individuals. A scoring algorithm using a low wake threshold is best suited for this population and setting.
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http://dx.doi.org/10.5664/jcsm.8162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053034PMC
February 2020

Effects of menopause on sleep quality and sleep disorders: Canadian Longitudinal Study on Aging.

Menopause 2020 03;27(3):295-304

Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, Montréal, Québec, Canada.

Objectives: Sleep complaints are common during the menopause transition. However, it is difficult to disentangle changes in sleep related to aging from those directly due to menopause. We compared sleep disorders in 45 to 60-year-old women in a large population-based study, according to menopausal status.

Methods: Women aged between 45 and 60 years who self-reported menopausal status were selected from the Canadian Longitudinal Study of Aging, excluding those with prior hysterectomy. Participants completed assessments for overall sleep satisfaction, hours of daily sleep, sleep-onset insomnia, sleep-maintenance insomnia, daytime somnolence, rapid eye movement sleep behavior disorder (RBD), restless leg syndrome (RLS), and obstructive sleep apnea (OSA). Each sleep variable was compared between postmenopausal and pre/perimenopausal women using multivariate regression, adjusting for potential confounders.

Results: Among 6,179 women included, 3,713 (60.1%; age 55.7 ± 3.3 years) were postmenopausal and 2,466 (39.9%) were pre/perimenopausal (age 49.80 ± 3.1 years). Compared with pre/perimenopausal women, postmenopausal women were more often reported requiring ≥30 minutes to fall asleep (20.4% vs 15.5%; adjusted odds ratio [AOR] 1.24, 95% confidence interval [CI] 1.00-1.53) and were more likely to meet criteria for possible sleep-onset insomnia disorder (10.8% vs 7.3%; AOR 1.51, 95% CI 1.07-2.12). Postmenopausal women were also more likely to screen positive for OSA (14.6% vs 10.4%; AOR 1.48, 95% CI 1.14-1.92). The two groups did not differ on sleep dissatisfaction (32.4% vs 29%), daytime somnolence disorder (1.6% vs 1.3%), sleep-maintenance insomnia disorder (17% vs 14.5%), RLS (23.5% vs 20.9%), or RBD (3.9% vs 4.0%).

Conclusions: Menopause is associated with increased sleep-onset insomnia. Postmenopausal women also are more likely to screen positive for OSA. However, menopausal status is not associated with sleep maintenance, somnolence, or RLS, and RBD. : Video Summary:http://links.lww.com/MENO/A501.
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http://dx.doi.org/10.1097/GME.0000000000001462DOI Listing
March 2020

EEG connectivity across sleep cycles and age.

Sleep 2020 03;43(3)

Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, Montréal, QC, Canada.

Study Objectives: In young adults, sleep is associated with important changes in cerebral connectivity during the first cycle of non-rapid eye movement (NREM) sleep. Our study aimed to evaluate how electroencephalography (EEG) connectivity during sleep differs between young and older individuals, and across the sleep cycles.

Methods: We used imaginary coherence to estimate EEG connectivity during NREM and rapid eye movement (REM) sleep in 30 young (14 women; 20-30 years) and 29 older (18 women; 50-70 years) individuals. We also explored the association between coherence and cognitive measures.

Results: Older individuals showed lower EEG connectivity in stage N2 but higher connectivity in REM and stage N3 compared to the younger cohort. Age-related differences in N3 were driven by the first sleep cycle. EEG connectivity was lower in REM than N3, especially in younger individuals. Exploratory analyses, controlling for the effects of age, indicated that higher EEG connectivity in delta during N2 was associated with higher processing speed, whereas, during REM sleep, lower EEG connectivity in delta and sigma was associated with higher verbal memory performance and a higher global averaged intelligence quotient score.

Conclusion: Our results indicated that age modifies sleep EEG connectivity but the direction and the magnitude of these effects differ between sleep stages and cycles. Results in N3 and REM point to a reduced ability of the older brains to disconnect as compared to the younger ones. Our results also support the notion that cerebral functional connectivity during sleep may be associated with cognitive functions.
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http://dx.doi.org/10.1093/sleep/zsz236DOI Listing
March 2020

Sleep-wake disturbances in hospitalized patients with traumatic brain injury: association with brain trauma but not with an abnormal melatonin circadian rhythm.

Sleep 2020 01;43(1)

Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, Montréal, Canada.

Study Objectives: To test whether the sleep-wake cycle disruption in patients hospitalized with traumatic brain injury (TBI) (1) is also found in patients with traumatic injuries other than TBI (non-TBI) and (2) is associated with a weaker or abnormal circadian clock signal.

Methods: Forty-two non-mechanically ventilated and non-sedated patients hospitalized for moderate-to-severe TBI were compared to 34 non-TBI patients. They wore wrist actigraphs for 9.4 ± 4.2 days, starting 19.3 ± 12.6 days post-injury. Of these, 17 TBI and 14 non-TBI patients had their urine collected every hour for 25 hours, starting 18.3 ± 12.3 days post-injury. We calculated urinary 6-sulfatoxymelatonin concentration to obtain total 24-hour excretion, excretion onset, offset, duration, amplitude, and acrophase. Using Student's t-tests, we compared groups on actigraphy (daytime activity ratio, nighttime total sleep time, and fragmentation index) and melatonin variables. We investigated associations between melatonin and actigraphy variables using Pearson's correlations.

Results: TBI patients had poorer daytime activity ratio (TBI: 77.5 ± 9.4%; non-TBI: 84.6 ± 6.9%), shorter nighttime total sleep time (TBI: 353.5 ± 96.6 min; non-TBI: 421.2 ± 72.2 min), and higher fragmentation index (TBI: 72.2 ± 30.0; non-TBI: 53.5 ± 23.6) (all p-values < 0.01). A melatonin rhythm was present in both groups, and no group differences were found on melatonin variables. No associations were found between melatonin and actigraphy variables in TBI patients.

Conclusion: Moderate-to-severe TBI patients have more serious sleep-wake disturbances than non-TBI patients hospitalized in the same environment, suggesting that the brain injury itself alters the sleep-wake cycle. Despite their deregulated 24-hour sleep-wake cycle, TBI patients have a normal circadian clock signal.
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http://dx.doi.org/10.1093/sleep/zsz191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955643PMC
January 2020

Investigating the incidence and magnitude of heterotopic ossification with and without joints involvement in patients with a limb fracture and mild traumatic brain injury.

Bone Rep 2019 Dec 13;11:100222. Epub 2019 Aug 13.

Centre de Recherche de l'Hôpital Sacré-Coeur de Montréal, Montréal, Québec, Canada.

Objectives: This study seeks to evaluate the incidence rate of heterotopic ossification (HO) formation in patients afflicted by an isolated limb fracture (ILF) and a concomitant mild traumatic brain injury (mTBI).

Methods: The current study is an observational study including ILF patients with or without a concomitant mTBI recruited from an orthopedic clinic of a Level 1 Trauma Hospital. Patients were diagnosed with a mTBI according to the American Congress of Rehabilitation Medicine (ACRM) criteria. Radiographs taken on average 3 months post-trauma were analyzed separately by two distinct specialists for the presence of HO proximally to the fracture site (joints or extra joints). Both raters referred to Brooker's and Della's Valle's classification to establish signs of HO. First, analyses were conducted for the full sample. Secondly, a matched cohort was used in order to control for specific factors, namely age, sex, type of injury, and time elapsed between the accident and the analyzed radiograph.

Results: The full sample included a total of 183 patients with an ILF (94 females; 47.5 years old), of which 50 had a concomitant mTBI and 133 without. Radiographic evidence of HO was significantly higher in patients with an ILF and a mTBI compared to ILF patients (X = 6.50;  = 0.01). The matched cohort consisted of 94 participants (i.e.; 47 patients from the ILF + mTBI group and 47 patients from the ILF group). Again, ILF + mTBI patients presented significantly higher rates of HO signs in comparison to ILF patients (X = 3.69;  = 0.04). Presence of HO was associated with prolonged delays to return to work (RTW) only in ILF + mTBI patients (F = 4.055;  = 0.05) but not in ILF patients (F = 0.823;  = 0.37).

Conclusions: Study findings suggest that rates of HO are significantly higher proximally to fracture sites when ILF patients sustain a concomitant mTBI, even after controlling for factors known to influence HO. Moreover, results show that HO is associated with a prolonged RTW only in ILF patients with a concomitant mTBI but not in ILF-only patients. The impact of mTBI on HO formation warrants further attention to detect early signs of HO, to identify shared physiopathological mechanisms and, ultimately, to design targeted therapies.
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http://dx.doi.org/10.1016/j.bonr.2019.100222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706636PMC
December 2019

Association between insomnia disorder and cognitive function in middle-aged and older adults: a cross-sectional analysis of the Canadian Longitudinal Study on Aging.

Sleep 2019 08;42(8)

Institut Universitaire de Geriatrie de Montreal and CRIUGM, CIUSSS du Centre-Sud-de-l'Ile-de-Montreal, Montreal, Canada.

Objectives: This study examined the differences in cognitive function between middle-aged and older adults with insomnia disorder, insomnia symptoms only (ISO) or no insomnia symptoms (NIS), in the context of other health and lifestyle factors.

Methods: Twenty-eight thousand four hundred eighty-five participants >45 years completed questionnaires, physical examinations, and neuropsychological testing across domains of processing speed, memory, and executive functions. An eight-question instrument assessed participants' sleep, defining subjects with insomnia symptoms, probable insomnia disorder (PID), or NIS. The associations between these three groups and cognitive performance were examined with linear regression models adjusted for lifestyle and clinical factors.

Results: PID was identified in 1,068 participants (3.7% of the sample) while 7,813 (27.5%) experienced ISO. Participants with PID exhibited greater proportions of adverse medical and lifestyle features such as anxiety, depression, and diabetes than both other groups. Analyses adjusting for age, sex, education, as well as medical and lifestyle factors demonstrated that adults with PID exhibited declarative memory deficits (Rey Auditory Verbal Learning Test) compared with ISO or NIS. Adults with insomnia symptoms exhibited better performance on a task of mental flexibility than both other groups.

Conclusions: These findings suggest that insomnia disorder in middle-aged and older adults is associated with poorer health outcomes and worse memory performance than adults with insomnia symptoms alone or without any sleep complaints, even after adjustment for comorbidities. The assessment of longitudinal data within this cohort will be critical to understand if insomnia disorder may increase the risk of further cognitive decline.
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http://dx.doi.org/10.1093/sleep/zsz114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685318PMC
August 2019

Disconnection Between Self-Reported and Objective Cognitive Impairment in Obstructive Sleep Apnea.

J Clin Sleep Med 2019 03 15;15(3):409-415. Epub 2019 Mar 15.

Centre for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada.

Study Objectives: Recent studies show that obstructive sleep apnea (OSA) is a possible contributor to abnormal cognitive decline in older adults. These new observations create the need to identify older adults with OSA who are at risk of the developing dementia if not treated. This study's goal was to verify whether self-reported cognitive complaints could become a useful tool to screen for objective cognitive deficits in late middle-aged and older adults with OSA.

Methods: Fifty-seven participants with OSA with an apnea-hypopnea index (AHI) ≥ 15 events/h (3% or arousal) and aged between 55 and 85 years were compared to 54 participants in a mild/non-OSA group on their ability to evaluate their objective cognitive functioning. They underwent overnight polysomnography followed by a comprehensive neuropsychological assessment. We recruited a similar proportion of participants with mild cognitive impairment (MCI) in both groups (OSA: 36.8%; mild/non-OSA: 35.2%). They filled out questionnaires assessing mood, sleep, and cognition. Group (OSA versus mild/non-OSA) × cognitive status (MCI versus non-MCI) analyses of variance were performed on cognitive complaint questionnaires.

Results: We found that among participants without objective cognitive deficits, participants in the OSA group reported more cognitive complaints compared to those in the mild/non-OSA group. Among participants with objective cognitive deficits, those in the OSA group reported less cognitive complaints compared to those in the mild/non-OSA group.

Conclusions: Participants with OSA and MCI were less aware of their deficits compared to those in the mild/non-OSA group, possibly reflecting a distinctive OSA-associated cognitive impairment. Our results underscore the importance of referring patients with OSA for a comprehensive neuropsychological assessment when an abnormal cognitive decline is suspected.
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http://dx.doi.org/10.5664/jcsm.7664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411171PMC
March 2019

A Longitudinal Investigation of Sleep and Daytime Wakefulness in Children and Youth With Concussion.

ASN Neuro 2019 Jan-Dec;11:1759091418822405

6 Montreal Children's Hospital, McGill University Health Center, Montreal, Québec, Canada.

A high proportion of adults who sustain a concussion identify changes in their sleep during the acute stage, typically reporting an increased need for sleep or nonrestful sleep. Our understanding of sleep following concussion is less well understood within a pediatric population. In this study, we investigated the trajectory of sleep and daytime sleepiness in a prospective cohort of 40 children and youth (6-18 years old) with concussion, 40 age-and sex-matched healthy children and youth, and 40 with upper-extremity orthopedic injury. Evaluations occurred during the acute stage (<2 weeks) and at 3-, 6-, and 12-month postinjury using the Sleep Disturbance Scale for Children and the Postconcussion Symptom Scale. There were no significant differences within- or between-group differences in sleep across all four time points with analysis of the groups as a whole. When groups were divided by age (6-11 and 12- < 18 years), there was a significant difference in the ability to initiate sleep for the younger concussed group during the acute stage, compared with healthy controls, as well as significantly greater daytime nap duration that decreased over time. Significant correlations were also found between the frequency and duration of daytime naps and Postconcussion Symptom Scale total score and subscores (cognitive, physical/migraine, mood, and sleep) in the concussed group during the acute stage. Our results suggest that in a group with noncomplicated concussion, children and youth have transient alterations in daytime sleepiness that are related to concussion symptoms. Younger children may be more vulnerable to disturbances in sleep and daytime wakefulness.
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http://dx.doi.org/10.1177/1759091418822405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343438PMC
April 2020

Sleep oscillation-specific associations with Alzheimer's disease CSF biomarkers: novel roles for sleep spindles and tau.

Mol Neurodegener 2019 02 21;14(1):10. Epub 2019 Feb 21.

Department of Psychiatry, NYU School of Medicine, New York, NY, 10016, USA.

Background: Based on associations between sleep spindles, cognition, and sleep-dependent memory processing, here we evaluated potential relationships between levels of CSF Aβ, P-tau, and T-tau with sleep spindle density and other biophysical properties of sleep spindles in a sample of cognitively normal elderly individuals.

Methods: One-night in-lab nocturnal polysomnography (NPSG) and morning to early afternoon CSF collection were performed to measure CSF Aβ, P-tau and T-tau. Seven days of actigraphy were collected to assess habitual total sleep time.

Results: Spindle density during NREM stage 2 (N2) sleep was negatively correlated with CSF Aβ, P-tau and T-tau. From the three, CSF T-tau was the most significantly associated with spindle density, after adjusting for age, sex and ApoE4. Spindle duration, count and fast spindle density were also negatively correlated with T-tau levels. Sleep duration and other measures of sleep quality were not correlated with spindle characteristics and did not modify the associations between sleep spindle characteristics and the CSF biomarkers of AD.

Conclusions: Reduced spindles during N2 sleep may represent an early dysfunction related to tau, possibly reflecting axonal damage or altered neuronal tau secretion, rendering it a potentially novel biomarker for early neuronal dysfunction. Given their putative role in memory consolidation and neuroplasticity, sleep spindles may represent a mechanism by which tau impairs memory consolidation, as well as a possible target for therapeutic interventions in cognitive decline.
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http://dx.doi.org/10.1186/s13024-019-0309-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385427PMC
February 2019

Brain white matter damage and its association with neuronal synchrony during sleep.

Brain 2019 03;142(3):674-687

Research center of the Hôpital du Sacré-Coeur de Montréal, Qc, Canada.

The restorative function of sleep partly relies on its ability to deeply synchronize cerebral networks to create large slow oscillations observable with EEG. However, whether a brain can properly synchronize and produce a restorative sleep when it undergoes massive and widespread white matter damage is unknown. Here, we answer this question by testing 23 patients with various levels of white matter damage secondary to moderate to severe traumatic brain injuries (ages 18-56; 17 males, six females, 11-39 months post-injury) and compared them to 27 healthy subjects of similar age and sex. We used MRI and diffusion tensor imaging metrics (e.g. fractional anisotropy as well as mean, axial and radial diffusivities) to characterize voxel-wise white matter damage. We measured the following slow wave characteristics for all slow waves detected in N2 and N3 sleep stages: peak-to-peak amplitude, negative-to-positive slope, negative and positive phase durations, oscillation frequency, and slow wave density. Correlation analyses were performed in traumatic brain injury and control participants separately, with age as a covariate. Contrary to our hypotheses, we found that greater white matter damage mainly over the frontal and temporal brain regions was strongly correlated with a pattern of higher neuronal synchrony characterized by slow waves of larger amplitudes and steeper negative-to-positive slopes during non-rapid eye movement sleep. The same pattern of associations with white matter damage was also observed with markers of high homeostatic sleep pressure. More specifically, higher white matter damage was associated with higher slow-wave activity power, as well as with more severe complaints of cognitive fatigue. These associations between white matter damage and sleep were found only in our traumatic brain injured participants, with no such correlation in controls. Our results suggest that, contrary to previous observations in healthy controls, white matter damage does not prevent the expected high cerebral synchrony during sleep. Moreover, our observations challenge the current line of hypotheses that white matter microstructure deterioration reduces cerebral synchrony during sleep. Our results showed that the relationship between white matter and the brain's ability to synchronize during sleep is neither linear nor simple.
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http://dx.doi.org/10.1093/brain/awy348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391600PMC
March 2019

Detection of mild cognitive impairment in middle-aged and older adults with obstructive sleep apnoea: does excessive daytime sleepiness play a role?

Eur Respir J 2019 01 3;53(1). Epub 2019 Jan 3.

Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Cœur de Montréal, Montréal, QC, Canada.

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http://dx.doi.org/10.1183/13993003.02113-2018DOI Listing
January 2019

Towards a better understanding of increased sleep duration in the chronic phase of moderate to severe traumatic brain injury: an actigraphy study.

Sleep Med 2019 07 28;59:67-75. Epub 2018 Nov 28.

Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, Montreal, Canada; Department of Psychology, Université de Montréal, Montreal, Canada. Electronic address:

Introduction: Most adults with moderate to severe traumatic brain injury (TBI) report persistent sleep-wake disturbances. Whether these complaints are either associated with abnormal sleep-wake patterns or can be explained by TBI-related characteristics is unclear. The present study aimed at characterising the subjective and objective sleep-wake patterns in TBI adults by taking into consideration the influence of TBI severity, common comorbidities and psychoactive medication.

Methods: Overall, 34 adults with moderate-severe TBI (one to four years post-injury) were compared to 34 controls. Sleepiness, fatigue, sleep quality, mood, and pain were assessed with questionnaires. A seven day sleep diary and actigraphy was used to document sleep and wake patterns.

Results: Compared to controls, TBI participants reported more sleepiness and fatigue, as well as poorer sleep quality. On actigraphy, they had earlier bedtime and longer time spent in bed, but equivalent sleep efficiency during the nighttime episode compared to controls. TBI participants also took more naps and accumulated more time asleep over the 24 h period than controls. These group differences were accentuated when only TBI adults using psychoactive medication were included. More comorbidities, more severe injuries and longer hospital stay were positively correlated with fatigue, sleepiness and sleep duration.

Conclusions: Our results showed that despite complaints regarding sleep and diurnal functioning, TBI survivors have very marginal changes in their objective sleep-wake schedules. Prolonged time spent in bed may reflect an attempt to increase their sleep duration in response to fatigue and sleepiness. TBI adults who use psychoactive medication are those with more evident changes in their sleep-wake schedules.
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http://dx.doi.org/10.1016/j.sleep.2018.11.012DOI Listing
July 2019

Obstructive sleep apnea during REM sleep and daytime cerebral functioning: A regional cerebral blood flow study using high-resolution SPECT.

J Cereb Blood Flow Metab 2020 06 22;40(6):1230-1241. Epub 2018 Nov 22.

Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur, Montreal, Canada.

Obstructive sleep apnea (OSA) predominantly during rapid eye movement (REM) sleep may have impacts on brain health, even in milder OSA cases. Here, we evaluated whether REM sleep OSA is associated with abnormal daytime cerebral functioning using high-resolution single-photon emission computed tomography (SPECT). We tested 96 subjects (25 F, age: 65.2 ± 6.4) with a wide range of OSA severity from no OSA to severe OSA (apnea-hypopnea index: 0-97 events/h). More respiratory events during REM sleep were associated with reduced daytime regional cerebral blood flow (rCBF) in the bilateral ventromedial prefrontal cortex and in the right insula extending to the frontal cortex. More respiratory events during non-REM (NREM) sleep were associated with reduced daytime rCBF in the left sensorimotor and temporal cortex. In subjects with a lower overall OSA severity (apnea-hypopnea index<15), more respiratory events during REM sleep were also associated with reduced daytime rCBF in the insula and extending to the frontal cortex. Respiratory events that characterized OSA during NREM versus REM sleep are associated with distinct patterns of daytime cerebral perfusion. REM sleep OSA could be more detrimental to brain health, as evidenced by reduced daytime rCBF in milder forms of OSA.
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http://dx.doi.org/10.1177/0271678X18814106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238367PMC
June 2020

Biomarkers of dementia in obstructive sleep apnea.

Sleep Med Rev 2018 12 13;42:139-148. Epub 2018 Aug 13.

Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, Montreal, Canada; Department of Psychology, Université de Montréal, Montreal, Canada. Electronic address:

Epidemiologic and mechanistic evidence is increasingly supporting the notion that obstructive sleep apnea is a risk factor for dementia. Hence, the identification of patients at risk of cognitive decline due to obstructive sleep apnea may significantly improve preventive strategies and treatment decision-making. Cerebrospinal fluid and blood biomarkers obtained through genomic, proteomic and metabolomic approaches are improving the ability to predict incident dementia. Therefore, fluid biomarkers have the potential to predict vulnerability to neurodegeneration in individuals with obstructive sleep apnea, as well as deepen our understanding of pathophysiological processes linking obstructive sleep apnea and dementia. Many fluid biomarkers linked to Alzheimer's disease and vascular dementia show abnormal levels in individuals with obstructive sleep apnea, suggesting that these conditions share common underlying mechanisms, including amyloid and tau protein neuropathology, inflammation, oxidative stress, and metabolic disturbances. Markers of these processes include amyloid-β, tau proteins, inflammatory cytokines, acute-phase proteins, antioxydants and oxidized products, homocysteine and clusterin (apolipoprotein J). Thus, these biomarkers may have the ability to identify adults with obstructive sleep apnea at high risk of dementia and provide an opportunity for therapeutic intervention. Large cohort studies are necessary to establish a specific fluid biomarker panel linking obstructive sleep apnea to dementia risk.
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http://dx.doi.org/10.1016/j.smrv.2018.08.001DOI Listing
December 2018

Detection of mild cognitive impairment in middle-aged and older adults with obstructive sleep apnoea.

Eur Respir J 2018 11 1;52(5). Epub 2018 Nov 1.

Centre for Advanced Research in Sleep Medicine (CARSM), Hôpital du Sacré-Coeur de Montréal, Montreal, QC, Canada.

Obstructive sleep apnoea increases the risk for mild cognitive impairment and dementia. The present study aimed to characterise the ability of two cognitive screening tests, the Mini-Mental State Examination and the Montreal Cognitive Assessment, to detect mild cognitive impairment in adults aged 55-85 years with and without obstructive sleep apnoea.We included 42 subjects with mild and 67 subjects with moderate-to-severe obstructive sleep apnoea. We compared them to 22 control subjects. Mild cognitive impairment was diagnosed by a comprehensive neuropsychological assessment. We used receiver operating characteristic curves to assess the ability of the two screening tests to detect mild cognitive impairment.The two screening tests showed similar discriminative ability in control subjects. However, among the mild and the moderate-to-severe obstructive sleep apnoea groups, the Mini-Mental State Examination was not able to correctly identify subjects with mild cognitive impairment. The Montreal Cognitive Assessment's discriminant ability was acceptable in both sleep apnoea groups and was comparable to what was observed in controls.The Mini-Mental State Examination should not be used to screen for cognitive impairment in patients with obstructive sleep apnoea. The Montreal Cognitive Assessment could be used in clinical settings. However, clinicians should refer patients for neuropsychological assessment when neurodegenerative processes are suspected.
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http://dx.doi.org/10.1183/13993003.01137-2018DOI Listing
November 2018

Obstructive Sleep Apnea and the Risk of Cognitive Decline in Older Adults.

Am J Respir Crit Care Med 2019 01;199(2):142-148

1 Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Cœur de Montréal, Montreal, Canada.

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http://dx.doi.org/10.1164/rccm.201801-0204PPDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943882PMC
January 2019
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