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result(s) for
"Djonlagic, Ina"
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Macro and micro sleep architecture and cognitive performance in older adults
by
Wood, Alexis C.
,
Luchsinger, José A.
,
Yaffe, Kristine
in
631/378/2612
,
692/308/174
,
692/53/2423
2021
We sought to determine which facets of sleep neurophysiology were most strongly linked to cognitive performance in 3,819 older adults from two independent cohorts, using whole-night electroencephalography. From over 150 objective sleep metrics, we identified 23 that predicted cognitive performance, and processing speed in particular, with effects that were broadly independent of gross changes in sleep quality and quantity. These metrics included rapid eye movement duration, features of the electroencephalography power spectra derived from multivariate analysis, and spindle and slow oscillation morphology and coupling. These metrics were further embedded within broader associative networks linking sleep with aging and cardiometabolic disease: individuals who, compared with similarly aged peers, had better cognitive performance tended to have profiles of sleep metrics more often seen in younger, healthier individuals. Taken together, our results point to multiple facets of sleep neurophysiology that track coherently with underlying, age-dependent determinants of cognitive and physical health trajectories in older adults.
In their analysis of two datasets, Djonlagic et al. identify 23 objective sleep metrics that predict cognitive performance and processing speed in older adults.
Journal Article
Association of novel measures of sleep disturbances with blood pressure: the Multi-Ethnic Study of Atherosclerosis
2020
BackgroundMechanisms underlying blood pressure (BP) changes in obstructive sleep apnoea (OSA) are incompletely understood. We assessed the associations between BP and selected polysomnography (PSG) traits: sleep depth, airflow limitation measurements and OSA-specific hypoxic burden.MethodsThis cross-sectional analysis included 2055 participants from the Multi-Ethnic Study of Atherosclerosis who underwent PSG and BP measurements in 2010–2013. Sleep depth was assessed using the ‘OR product’, a continuous measure of arousability. Airflow limitation was assessed by duty cycle (Ti/Tt) and % of breaths with flow limitation, and hypoxia by ‘hypoxic burden’. Primary outcomes were medication-adjusted systolic BP (SBP) and diastolic BP (DBP). We used generalised linear models adjusted for age, sex, race/ethnicity, smoking, education, body mass index, alcohol use, periodic limb movements and alternative physiological disturbances.ResultsThe sample had a mean age of 68.4 years and apnoea–hypopnoea index of 14.8 events/hour. Sleep depth was not significantly associated with BP. Every 1 SD increment in log-transformed non-rapid eye movement duty cycle was associated with 0.9% decrease in SBP (95% CI: 0.1% to 1.6%), even after adjusting for sleep depth and hypoxic burden. Every 1 SD increment in log-transformed hypoxic burden was associated with a 1.1% increase in SBP (95% CI: 0.1% to 2.1%) and 1.9% increase in DBP (95% CI: 1.0% to 2.8%) among those not using hypertension medications.ConclusionsHigher duty cycle was associated with lower SBP overall and hypoxic burden with higher SBP and DBP among non-BP medication users. These findings suggest changes in both respiratory effort and oxygenation during sleep influence BP.
Journal Article
Increased Sleep Fragmentation Leads to Impaired Off-Line Consolidation of Motor Memories in Humans
2012
A growing literature supports a role for sleep after training in long-term memory consolidation and enhancement. Consequently, interrupted sleep should result in cognitive deficits. Recent evidence from an animal study indeed showed that optimal memory consolidation during sleep requires a certain amount of uninterrupted sleep. Sleep continuity is disrupted in various medical disorders. We compared performance on a motor sequence learning task (MST) in relatively young subjects with obstructive sleep apnea (n = 16; apnea-hypopnea index 17.1±2.6/h [SEM]) to a carefully matched control group (n = 15, apnea-hypopnea index 3.7±0.4/h, p<0.001. Apart from AHI, oxygen nadir and arousal index, there were no significant differences between groups in total sleep time, sleep efficiency and sleep architecture as well as subjective measures of sleepiness based on standard questionnaires. In addition performance on the psychomotor vigilance task (reaction time and lapses), which is highly sensitive to sleep deprivation showed no differences as well as initial learning performance during the training phase. However there was a significant difference in the primary outcome of immediate overnight improvement on the MST between the two groups (controls = 14.7±4%, patients = 1.1±3.6%; P = 0.023) as well as plateau performance (controls = 24.0±5.3%, patients = 10.1±2.0%; P = 0.017) and this difference was predicted by the arousal index (p = 0.02) rather than oxygen saturation (nadir and time below 90% saturation. Taken together, this outcome provides evidence that there is a clear minimum requirement of sleep continuity in humans to ensure optimal sleep dependent memory processes. It also provides important new information about the cognitive impact of obstructive sleep apnea and challenges its current definitions.
Journal Article
Untreated Sleep-Disordered Breathing: Links to Aging-Related Decline in Sleep-Dependent Memory Consolidation
2014
Increasing age is associated with a decline in cognition and motor skills, while at the same time exacerbating one's risk of developing obstructive sleep apnea (OSA). OSA-related cognitive deficits are highly prevalent and can affect various memory systems including overnight memory consolidation on a motor sequence task. Thus, the aim of our study was to examine the effect of aging on sleep-dependent motor memory consolidation in patients with and without OSA.
We studied 44 patients (19-68 years) who had been referred by a physician for a baseline polysomnography (PSG) evaluation. Based on their PSG, patients were assigned either to the OSA group (AHI>5/h), or control (Non-OSA) group (AHI<5/h). All subjects performed the Psychomotor Vigilance Task (PVT) and the Motor Sequence Learning Task (MST) in the evening and again in the morning after their PSG.
Despite similar learning in the evening, OSA subjects showed significantly less overnight improvement on the MST, both for immediate (OSA -2.7% ± 2.8% vs. controls 12.2% ± 3.5%; p = 0.002) and plateau improvement (OSA 4.9% ± 2.3% vs. controls 21.1%± 4.0%; p = 0.001). Within the OSA group, there was a significant negative correlation between overnight MST improvement and age (r(2) = 0.3; p = 0.01), an effect that was not observed in the Non-OSA group (r(2) = 0.08; p = 0.23).
Consistent with previous research, healthy sleepers demonstrated a higher degree of sleep-dependent overnight improvement on the MST, an effect not mitigated by increasing age. However, the presence of untreated obstructive sleep apnea is associated with an aging-related cognitive deficit, otherwise not present in individuals without OSA. As other research has linked the presence of OSA to a higher likelihood of developing dementia, future studies are necessary to examine if the inhibition of memory consolidation is tied to the onset of neurodegenerative disease.
Journal Article
Brainstem lesions are associated with sleep apnea in multiple sclerosis
by
Baber, Ursela
,
Djonlagic, Ina
,
Levit, Elle
in
Lesions
,
Multiple sclerosis
,
Original Research Paper
2020
Background
Studies linking MRI findings in MS patients with obstructive sleep apnea severity are limited.
Objective
We conducted a retrospective study to assess MRI abnormalities associated with obstructive sleep apnea (OSA) in patients with multiple sclerosis (MS).
Methods
We performed retrospective chart review of 65 patients with multiple sclerosis who had undergone polysomnography (PSG) for fatigue as well as brain MRI. We measured the number of lesions in the brainstem and calculated the standardized third ventricular width (sTVW) as a measure of brain atrophy, and subsequently performed correlation analyses of the apnea-hypopnea index (AHI) with brainstem lesion location, sTVW, and Expanded Disability Status Scale (EDSS).
Results
MS Patients with OSA were significantly older and had a higher body mass index (BMI) and higher AHI measures than patients without OSA. After adjustment for covariates, significant associations were found between AHI and lesion burden in the midbrain (p < 0.01) and pons (p = 0.05), but not medulla.
Conclusions
Midbrain and pontine lesions burden correlated with AHI, suggesting MS lesion location could contribute to development of OSA.
Journal Article
Amyloid beta–independent sleep markers associated with early regional tau burden and cortical thinning
by
Stankeviciute, Laura
,
Chhatwal, Jasmeer P.
,
Pinilla, Valentina
in
Alzheimer's disease
,
amyloid positron emission tomography
,
Brain research
2024
INTRODUCTION Sleep is crucial for memory consolidation and the clearance of toxic proteins associated with Alzheimer's disease (AD). We examined the association between sleep characteristics and imaging biomarkers of early amyloid beta (Aβ) and tau pathology as well as neurodegeneration in brain regions known to be affected in the incipient stages of AD. METHODS Thirty‐nine cognitively unimpaired (CU) participants of the Harvard Aging Brain Study underwent at‐home polysomnography as well as tau positron emission tomography (flortaucipir‐PET), amyloid PET (Pittsburgh compound B [PiB]‐PET), and magnetic resonance imaging–derived assessment of cortical thickness (CT). RESULTS Increased N1 sleep was associated with a higher tau PET signal (β = 0.009, p = 0.001) and lower CT in the temporal composite region of interest (β = –0.017, p = 0.007). Decreased slow‐wave sleep (SWS) was associated with higher tau burden in the temporal composite (β = –0.008, p = 0.005) and lower CT (β = 0.008, p = 0.002), even after controlling for global PiB‐PET. DISCUSSION In CU older adults, lower SWS and higher N1 sleep were associated with higher tau burden and lower CT in brain regions associated with early tau deposition and vulnerable to AD‐related neurodegeneration through mechanisms dissociable from amyloid deposition. Highlights We report the results of an observational study, which leveraged ‐a well‐characterized cohort of healthy aging (Harvard Aging Brain Study) by adding in‐home full polysomnograms. By adding at‐home polysomnograms to this unique and deeply phenotyped cohort, we examined variations in sleep architecture that are associated with Alzheimer's disease (AD) pathologic changes. Our results confirmed the association of sleep changes with early tau and cortical neurodegenerative changes that were independent of amyloid. The results will be of importance in monitoring sleep‐related variations in relation to the natural history of AD pathology and in designing sleep‐focused clinical trials.
Journal Article
REM-related obstructive sleep apnea: when does it matter? Effect on motor memory consolidation versus emotional health
2020
Study Objectives:
The clinical importance of obstructive sleep apnea, which can be prevalent during rapid eye movement (REM) sleep, is unclear. The current study examines the effect of REM-related obstructive sleep apnea on motor memory consolidation as well as on mood states.
Methods:
We compared performance on the motor sequence task (MST), psychomotor vigilance test (PVT), Functional Outcomes of Sleep Questionnaire, and the Profile of Mood State (POMS) survey between 3 groups: healthy controls (n = 18), REM-exclusive OSA (n = 17), and patients with OSA with respiratory events throughout REM and non-rapid eye movement (NREM) sleep (n = 18).
Results:
As expected, performance on the MST improved overnight in the healthy control group. An improvement which was similar in magnitude was also observed in the REM-exclusive OSA group whereas patients with similar OSA during REM and NREM sleep showed reduced overnight memory consolidation. Consistent with these results, we found a correlation between overnight MST improvement and the apnea hypopnea index during NREM sleep (
P
= .041), but not during REM sleep (
P
= .424). However, patients with REM-exclusive apnea demonstrated the most negative emotions based on scoring highest on the POMS survey (
P
= .019).
Conclusions:
Our results provide evidence that although apneas occurring only during REM sleep do not have an effect on the encoding and stabilization of motor sequence memories, they are deleterious for emotional health.
Citation:
Djonlagic I, Guo M, Igue M, Malhotra A, Stickgold R. REM-related obstructive sleep apnea: when does it matter? Effect on motor memory consolidation versus emotional health.
J Clin Sleep Med
. 2020;16(3):377–384.
Journal Article
Publisher Correction: Macro and micro sleep architecture and cognitive performance in older adults
by
Wood, Alexis C.
,
Luchsinger, José A.
,
Yaffe, Kristine
in
631/378/2612
,
692/308/174
,
692/53/2423
2021
A Correction to this paper has been published: https://doi.org/10.1038/s41562-020-01030-3.
Journal Article
Normalized electroencephalogram power: a trait with increased risk of dementia
by
Younes, Magdy
,
Peters, Katherine
,
Djonlagic, Ina
in
Dementia - etiology
,
Electroencephalography
,
Humans
2023
Graphical Abstract
Graphical Abstract
Journal Article
Effect of daridorexant on sleep architecture in patients with chronic insomnia disorder: a pooled post hoc analysis of two randomized phase 3 clinical studies
by
Hubbard, Jeffrey
,
Di Marco, Tobias
,
Krystal, Andrew
in
Adult
,
Care and treatment
,
Clinical trials
2024
Abstract
Study Objectives
Post hoc analysis to evaluate the effect of daridorexant on sleep architecture in people with insomnia, focusing on features associated with hyperarousal.
Methods
We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). We analyzed sleep–wake transition probabilities, EEG spectra, and sleep spindle properties including density, dispersion, and slow oscillation phase coupling. The wake EEG similarity index (WESI) was determined using a machine learning algorithm analyzing the spectral profile of the EEG.
Results
At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities (p < .05) and increased the probability of transitions from wake-to-N1 (p < .05), N2 (p < .05), and REM sleep (p < .05), as well as from N1-to-N2 (p < .05) compared to baseline and placebo. Daridorexant 50 mg decreased relative beta power during wake (p = .011) and N1 (p < .001) compared to baseline and placebo. During the wake, relative alpha power decreased (p < .001) and relative delta power increased (p < .001) compared to placebo. Daridorexant did not alter EEG spectra bands in N2, N3, and REM stages or in sleep spindle activity. Daridorexant decreased the WESI score during wake compared to baseline (p = .004). Effects with 50 mg were consistent between months 1 and 3 and less pronounced with 25 mg.
Conclusions
Daridorexant reduced EEG features associated with hyperarousal as indicated by reduced wake-to-wake transition probabilities and enhanced spectral features associated with drowsiness and sleep during wake and N1.
Clinical Trials
ClinicalTrials.gov NCT03545191: study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants with insomnia disorder. URL: Study Details | study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants with insomnia disorder | ClinicalTrials.gov ClinicalTrials.gov NCT03575104:
study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants who experience difficulties sleeping. URL: study details | study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants who experience difficulties sleeping | ClinicalTrials.gov
Graphical Abstract
Graphical Abstract
Journal Article