Evaluating possible 'next day' impairment in insomnia patients administered an oral medicinal cannabis product by night: a pilot randomized controlled trial.

Cannabis and its major constituents, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are being widely used to treat sleep disturbances. However, THC can cause acute cognitive and psychomotor impairment and there are concerns that driving and workplace safety might be compromised the day after evening use. Here, we examined possible 'next day' impairment following evening administration of a typical medicinal cannabis oil in adults with insomnia disorder, compared to matched placebo. This paper describes the secondary outcomes of a larger study investigating the effects of THC/CBD on insomnia disorder. Twenty adults [16 female; mean (SD) age, 46.1 (8.6) y] with physician-diagnosed insomnia who infrequently use cannabis completed two 24 h in-laboratory visits involving acute oral administration of combined 10 mg THC and 200 mg CBD ('THC/CBD') or placebo in a randomised, double-blind, crossover trial design. Outcome measures included 'next day' (≥9 h post-treatment) performance on cognitive and psychomotor function tasks, simulated driving performance, subjective drug effects, and mood. We found no differences in 'next day' performance on 27 out of 28 tests of cognitive and psychomotor function and simulated driving performance relative to placebo. THC/CBD produced a small decrease (-1.4%, p=.016, d=-0.6) in accuracy on the Stroop-Colour Task (easy/congruent) but not the Stroop-Word Task (hard/incongruent). THC/CBD also produced a small increase (+8.6, p=.042, d=0.3) in self-ratings of Sedated at 10 h post-treatment, but with no accompanying changes in subjective ratings of Alert or Sleepy (p's>0.05). In conclusion, we found a lack of notable 'next day' impairment to cognitive and psychomotor function and simulated driving performance following evening use of 10 mg oral THC, in combination with 200 mg CBD, in an insomnia population who infrequently use cannabis.

Electroencephalographic slowing during REM sleep in older adults with subjective cognitive impairment and mild cognitive impairment.

STUDY OBJECTIVES: In older adults with Alzheimer's disease, slowing of electroencephalographic (EEG) activity during REM sleep has been observed. Few studies have examined EEG slowing during REM in those with mild cognitive impairment (MCI) and none have examined its relationship with cognition in this at-risk population. METHODS: Two hundred and ten older adults (mean age = 67.0, SD = 8.2 years) underwent comprehensive neuropsychological, medical, and psychiatric assessment and overnight polysomnography. Participants were classified as subjective cognitive impairment (SCI; n = 75), non-amnestic MCI (naMCI, n = 85), and amnestic MCI (aMCI, n = 50). REM EEG slowing was defined as (δ + θ)/(α + σ + ß) power and calculated for frontal, central, parietal, and occipital regions. Analysis of variance compared REM EEG slowing between groups. Correlations between REM EEG slowing and cognition, including learning and memory, visuospatial and executive functions, were examined within each subgroup. RESULTS: The aMCI group had significantly greater REM EEG slowing in the parietal and occipital regions compared to the naMCI and SCI groups (partial η2 = 0.06, p < 0.05 and 0.06, p < 0.05, respectively), and greater EEG slowing in the central region compared to SCI group (partial η2 = 0.03, p < 0.05). Greater REM EEG slowing in parietal (r = -0.49) and occipital regions (r = -0.38 [O1/M2] and -0.33 [O2/M1]) were associated with poorer visuospatial performance in naMCI. CONCLUSIONS: REM EEG slowing may differentiate older adults with memory impairment from those without. Longitudinal studies are now warranted to examine the prognostic utility of REM EEG slowing for cognitive and dementia trajectories.

Predicting neurodegeneration from sleep related biofluid changes.

Sleep-wake disturbances are common in neurodegenerative diseases and may occur years before the clinical diagnosis, potentially either representing an early stage of the disease itself or acting as a pathophysiological driver. Therefore, discovering biomarkers that identify individuals with sleep-wake disturbances who are at risk of developing neurodegenerative diseases will allow early diagnosis and intervention. Given the association between sleep and neurodegeneration, the most frequently analyzed fluid biomarkers in people with sleep-wake disturbances to date include those directly associated with neurodegeneration itself, such as neurofilament light chain, phosphorylated tau, amyloid-beta and alpha-synuclein. Abnormalities in these biomarkers in patients with sleep-wake disturbances are considered as evidence of an underlying neurodegenerative process. Levels of hormonal sleep-related biomarkers such as melatonin, cortisol and orexin are often abnormal in patients with clinical neurodegenerative diseases, but their relationships with the more standard neurodegenerative biomarkers remain unclear. Similarly, it is unclear whether other chronobiological/circadian biomarkers, such as disrupted clock gene expression, are causal factors or a consequence of neurodegeneration. Current data would suggest that a combination of fluid biomarkers may identify sleep-wake disturbances that are most predictive for the risk of developing neurodegenerative disease with more optimal sensitivity and specificity.

Assessing sleep architecture and cognition in older adults with depressive symptoms attending a memory clinic.

BACKGROUND: While depression is intrinsically and bidirectionally linked with both sleep disturbance and cognition, the inter-relationships between sleep, cognition, and brain integrity in older people with depression, especially those with late-onset depression are undefined. METHODS: One hundred and seventy-two older adults (mean age 64.3 ± 6.9 years, Depression: n = 66, Control: n = 106) attending a memory clinic underwent a neuropsychological battery of declarative memory, executive function tasks, cerebral magnetic resonance imaging and overnight polysomnography with quantitative electroencephalography. RESULTS: The time spent in slow-wave sleep (SWS) and rapid eye movement (REM) sleep, slow-wave activity, sleep spindles, hippocampal volume and prefrontal cortex thickness did not differ between depression and control and depression onset groups. However, sleep onset latency (p = 0.005) and REM onset latency (p = 0.02) were later in the Depression group compared to controls. Less SWS was associated with poorer memory (r = 0.31, p = 0.023) in the depression group, and less SWS was related to better memory in the control group (r = -0.20, p = 0.043; Fishers r-to-z = -3.19). LIMITATIONS: Longitudinal studies are needed to determine if changes in sleep in those with depressive symptoms predict cognitive decline and illness trajectory. CONCLUSION: Older participants with depressive symptoms had delayed sleep initiation, suggestive of delayed sleep phase. The association between SWS and memory suggests SWS may be a useful target for cognitive intervention in older adults with depression symptoms. Reduced hippocampal volumes did not mediate this relationship, indicating a broader distributed neural network may underpin these associations.

Sleep spindle architecture associated with distinct clinical phenotypes in older adults at risk for dementia.

Sleep spindles are a hallmark of non-REM sleep and play a fundamental role in memory consolidation. Alterations in these spindles are emerging as sensitive biomarkers for neurodegenerative diseases of ageing. Understanding the clinical presentations associated with spindle alterations may help to elucidate the functional role of these distinct electroencephalographic oscillations and the pathophysiology of sleep and neurodegenerative disorders. Here, we use a data-driven approach to examine the sleep, memory and default mode network connectivity phenotypes associated with sleep spindle architecture in older adults (mean age = 66 years). Participants were recruited from a specialist clinic for early diagnosis and intervention for cognitive decline, with a proportion showing mild cognitive deficits on neuropsychological testing. In a sample of 88 people who underwent memory assessment, overnight polysomnography and resting-state fMRI, a k-means cluster analysis was applied to spindle measures of interest: fast spindle density, spindle duration and spindle amplitude. This resulted in three clusters, characterised by preserved spindle architecture with higher fast spindle density and longer spindle duration (Cluster 1), and alterations in spindle architecture (Clusters 2 and 3). These clusters were further characterised by reduced memory (Clusters 2 and 3) and nocturnal hypoxemia, associated with sleep apnea (Cluster 3). Resting-state fMRI analysis confirmed that default mode connectivity was related to spindle architecture, although directionality of this relationship differed across the cluster groups. Together, these results confirm a diversity in spindle architecture in older adults, associated with clinically meaningful phenotypes, including memory function and sleep apnea. They suggest that resting-state default mode connectivity during the awake state can be associated with sleep spindle architecture; however, this is highly dependent on clinical phenotype. Establishing relationships between clinical and neuroimaging features and sleep spindle alterations will advance our understanding of the bidirectional relationships between sleep changes and neurodegenerative diseases of ageing.

Region-specific changes in brain activity and memory after continuous positive airway pressure therapy in obstructive sleep apnea: a pilot high-density electroencephalography study.

STUDY OBJECTIVES: Limited channel electroencephalography (EEG) investigations in obstructive sleep apnea (OSA) have revealed deficits in slow wave activity (SWA) and spindles during sleep and increased EEG slowing during resting wakefulness. High-density EEG (Hd-EEG) has also detected local parietal deficits in SWA (delta power) during NREM. It is unclear whether effective continuous positive airway pressure (CPAP) treatment reverses regional SWA deficits, and other regional sleep and wake EEG abnormalities, and whether any recovery relates to improved overnight memory consolidation. METHODS: A clinical sample of men with moderate-severe OSA underwent sleep and resting wake recordings with 256-channel Hd-EEG before and after 3 months of CPAP. Declarative and procedural memory tasks were administered pre- and post-sleep. Topographical spectral power maps and differences between baseline and treatment were compared using t-tests and statistical nonparametric mapping (SnPM). RESULTS: In 11 compliant CPAP users (5.2 ±â€…1.1 hours/night), total sleep time did not differ after CPAP but N1 and N2 sleep were lower and N3 was higher. Centro-parietal gamma power during N3 increased and fronto-central slow spindle activity during N2 decreased (SnPM < 0.05). No other significant differences in EEG power were observed. When averaged specifically within the parietal region, N3 delta power increased after CPAP (p = 0.0029) and was correlated with the change in overnight procedural memory consolidation (rho = 0.79, p = 0.03). During resting wakefulness, there were trends for reduced delta and theta power. CONCLUSIONS: Effective CPAP treatment of OSA may correct regional EEG abnormalities, and regional recovery of SWA may relate to procedural memory improvements in the short term.

Cannabinol (CBN; 30 and 300 mg) effects on sleep and next-day function in insomnia disorder ('CUPID' study): protocol for a randomised, double-blind, placebo-controlled, cross-over, three-arm, proof-of-concept trial.

OBJECTIVE: Insomnia is the most prevalent sleep disorder, with few effective pharmacotherapies. Anecdotal reports and recent preclinical research suggest that cannabinol (CBN), a constituent of Cannabis sativa derived from delta-9-tetrahydrocannabinol, could be an effective treatment. Despite this, the isolated effects of CBN on sleep have yet to be systematically studied in humans. METHODS: The present protocol paper describes a randomised, double-blind, placebo-controlled, single-dose, three-arm, cross-over, proof-of-concept study which investigates the effects of CBN on sleep and next-day function in 20 participants with clinician-diagnosed insomnia disorder and an Insomnia Severity Index Score ≥15. Participants receive a single fixed oral liquid dose of 30 mg CBN, 300 mg CBN and matched placebo, in random order on three treatment nights; each separated by a 2-week wash-out period. Participants undergo overnight sleep assessment using in-laboratory polysomnography and next-day neurobehavioural function tests. The primary outcome is wake after sleep onset minutes. Secondary outcomes include changes to traditional sleep staging, sleep-onset latency and absolute spectral power during non-rapid eye movement (NREM) sleep. Tertiary outcomes include changes to sleep spindles during NREM sleep, arousal indices, absolute spectral power during REM sleep and subjective sleep quality. Safety-related and exploratory outcomes include changes to next-day simulated driving performance, subjective mood and drug effects, postural sway, alertness and reaction time, overnight memory consolidation, pre and post-sleep subjective and objective sleepiness; and plasma, urinary, and salivary cannabinoid concentrations. The study will provide novel preliminary data on CBN efficacy and safety in insomnia disorder, which will inform larger clinical trials. ETHICS AND DISSEMINATION: Human Research Ethics Committee approval has been granted by Bellberry (2021-08-907). Study findings will be disseminated in a peer-reviewed journal and at academic conferences. TRIAL REGISTRATION NUMBER: NCT05344170.

The association between sleep spindles and cognitive function in middle-aged and older men from a community-based cohort study.

OBJECTIVES: Previous studies examining associations between sleep spindles and cognitive function attempted to account for obstructive sleep apnea without consideration for potential moderating effects. To elucidate associations between sleep spindles, cognitive function, and obstructive sleep apnea, this study of community-dwelling men examined cross-sectional associations between sleep spindle metrics and daytime cognitive function outcomes following adjustment for obstructive sleep apnea and potential obstructive sleep apnea moderating effects. METHODS: Florey Adelaide Male Ageing Study participants (n = 477, 41-87 years) reporting no previous obstructive sleep apnea diagnosis underwent home-based polysomnography (2010-2011). Cognitive testing (2007-2010) included the inspection time task (processing speed), trail-making tests A (TMT-A) (visual attention) and B (trail-making test-B) (executive function), and Fuld object memory evaluation (episodic memory). Frontal spindle metrics (F4-M1) included occurrence (count), average frequency (Hz), amplitude (µV), and overall (11-16 Hz), slow (11-13 Hz), and fast (13-16 Hz) spindle density (number/minute during N2 and N3 sleep). RESULTS: In fully adjusted linear regression models, lower N2 sleep spindle occurrence was associated with longer inspection times (milliseconds) (B = -0.43, 95% confidence interval [-0.74, -0.12], p = .006), whereas higher N3 sleep fast spindle density was associated with worse TMT-B performance (seconds) (B = 18.4, 95% confidence interval [1.62, 35.2], p = .032). Effect moderator analysis revealed that in men with severe obstructive sleep apnea (apnea-hypopnea index ≥30/hour), slower N2 sleep spindle frequency was associated with worse TMT-A performance (χ2 = 12.5, p = .006). CONCLUSIONS: Specific sleep spindle metrics were associated with cognitive function, and obstructive sleep apnea severity moderated these associations. These observations support the utility of sleep spindles as useful cognitive function markers in obstructive sleep apnea, which warrants further longitudinal investigation.

Heart rate variability during slow wave sleep is linked to functional connectivity in the central autonomic network.

Reduced heart rate variability can be an early sign of autonomic dysfunction in neurodegenerative diseases and may be related to brain dysfunction in the central autonomic network. As yet, such autonomic dysfunction has not been examined during sleep-which is an ideal physiological state to study brain-heart interaction as both the central and peripheral nervous systems behave differently compared to during wakefulness. Therefore, the primary aim of the current study was to examine whether heart rate variability during nocturnal sleep, specifically slow wave (deep) sleep, is associated with central autonomic network functional connectivity in older adults 'at-risk' of dementia. Older adults (n = 78; age range = 50-88 years; 64% female) attending a memory clinic for cognitive concerns underwent resting-state functional magnetic resonance imaging and an overnight polysomnography. From these, central autonomic network functional connectivity strength and heart rate variability data during sleep were derived, respectively. High-frequency heart rate variability was extracted to index parasympathetic activity during distinct periods of sleep, including slow wave sleep as well as secondary outcomes of non-rapid eye movement sleep, wake after sleep onset, and rapid eye movement sleep. General linear models were used to examine associations between central autonomic network functional connectivity and high-frequency heart rate variability. Analyses revealed that increased high-frequency heart rate variability during slow wave sleep was associated with stronger functional connectivity (F = 3.98, P = 0.022) in two core brain regions within the central autonomic network, the right anterior insular and posterior midcingulate cortex, as well as stronger functional connectivity (F = 6.21, P = 0.005) between broader central autonomic network brain regions-the right amygdala with three sub-nuclei of the thalamus. There were no significant associations between high-frequency heart rate variability and central autonomic network connectivity during wake after sleep onset or rapid eye movement sleep. These findings show that in older adults 'at-risk' of dementia, parasympathetic regulation during slow wave sleep is uniquely linked to differential functional connectivity within both core and broader central autonomic network brain regions. It is possible that dysfunctional brain-heart interactions manifest primarily during this specific period of sleep known for its role in memory and metabolic clearance. Further studies elucidating the pathophysiology and directionality of this relationship should be conducted to determine if heart rate variability drives neurodegeneration, or if brain degeneration within the central autonomic network promotes aberrant heart rate variability.

Associations of Baseline Sleep Microarchitecture with Cognitive Function After 8 Years in Middle-Aged and Older Men from a Community-Based Cohort Study.

Purpose: Prospective studies examining associations between baseline sleep microarchitecture and future cognitive function recruited from small samples with predominantly short follow-up. This study examined sleep microarchitecture predictors of cognitive function (visual attention, processing speed, and executive function) after 8 years in community-dwelling men. Patients and Methods: Florey Adelaide Male Ageing Study participants (n=477) underwent home-based polysomnography (2010-2011), with 157 completing baseline (2007-2010) and follow-up (2018-2019) cognitive assessments (trail-making tests A [TMT-A] and B [TMT-B] and the standardized mini-mental state examination [SMMSE]). Whole-night F4-M1 sleep EEG recordings were processed following artifact exclusion, and quantitative EEG characteristics were obtained using validated algorithms. Associations between baseline sleep microarchitecture and future cognitive function (visual attention, processing speed, and executive function) were examined using linear regression models adjusted for baseline obstructive sleep apnoea, other risk factors, and cognition. Results: The final sample included men aged (mean [SD]) 58.9 (8.9) years at baseline, overweight (BMI 28.5 [4.2] kg/m2), and well educated (75.2% ≥Bachelor, Certificate, or Trade), with majorly normal baseline cognition. Median (IQR) follow-up was 8.3 (7.9, 8.6) years. In adjusted analyses, NREM and REM sleep EEG spectral power was not associated with TMT-A, TMT-B, or SMMSE performance (all p>0.05). A significant association of higher N3 sleep fast spindle density with worse TMT-B performance (B=1.06, 95% CI [0.13, 2.00], p=0.026) did not persist following adjustment for baseline TMT-B performance. Conclusion: In this sample of community-dwelling men, sleep microarchitecture was not independently associated with visual attention, processing speed, or executive function after 8 years.

Overnight declarative memory consolidation and non-rapid eye movement sleep electroencephalographic oscillations in older adults with obstructive sleep apnea.

STUDY OBJECTIVES: To compare overnight declarative memory consolidation and non-rapid eye movement (NREM) sleep electroencephalogram (EEG) oscillations in older adults with obstructive sleep apnea (OSA) to a control group and assess slow-wave activity (SWA) and sleep spindles as correlates of memory consolidation. METHODS: Forty-six older adults (24 without OSA and 22 with OSA) completed a word-pair associate's declarative memory task before and after polysomnography. Recall and recognition were expressed as a percentage of the morning relative to evening scores. Power spectral analysis was performed on EEG recorded at frontal (F3-M2, F4-M1) and central (C3-M2, C4-M1) sites. We calculated NREM absolute slow oscillation (0.25-1 Hz) and delta (0.5-4.5 Hz) EEG power, and slow (11-13 Hz) spindle density (number of events per minute of N2 sleep) and fast (13-16 Hz) spindle density. RESULTS: There were no significant differences in overnight recall and recognition between OSA (mean age 58.7 ± 7.1 years, apnea-hypopnea index (AHI) 41.9 ± 29.7 events/hour) and non-OSA (age 61.1 ± 10.3 years, AHI 6.6 ± 4.2 events/hour) groups. The OSA group had lower fast spindle density in the frontal region (p = 0.007). No between-group differences in SWA were observed. In the Control group, overnight recognition positively correlated with slow spindle density in frontal (rho = 0.555, p = 0.020) and central regions (rho = 0.490, p = 0.046). Overnight recall was not related to SWA or spindle measures in either group. CONCLUSIONS: Older adults with OSA had deficits in fast sleep spindles but showed preserved overnight declarative memory consolidation. It is possible that compensatory mechanisms are being recruited by OSA patients to preserve declarative memory consolidation despite the presence of sleep spindle deficits.

The Health Effects of 72 Hours of Simulated Wind Turbine Infrasound: A Double-Blind Randomized Crossover Study in Noise-Sensitive, Healthy Adults.

BACKGROUND: Large electricity-generating wind turbines emit both audible sound and inaudible infrasound at very low frequencies that are outside of the normal human range of hearing. Sufferers of wind turbine syndrome (WTS) have attributed their ill-health and particularly their sleep disturbance to the signature pattern of infrasound. Critics have argued that these symptoms are psychological in origin and are attributable to nocebo effects. OBJECTIVES: We aimed to test the effects of 72 h of infrasound (1.6-20 Hz at a sound level of ∼90 dB pk re 20µPa, simulating a wind turbine infrasound signature) exposure on human physiology, particularly sleep. METHODS: We conducted a randomized double-blind triple-arm crossover laboratory-based study of 72 h exposure with a >10-d washout conducted in a noise-insulated sleep laboratory in the style of a studio apartment. The exposures were infrasound (∼90 dB pk), sham infrasound (same speakers not generating infrasound), and traffic noise exposure [active control; at a sound pressure level of 40-50 dB LAeq,night and 70 dB LAFmax transient maxima, night (2200 to 0700 hours)]. The following physiological and psychological measures and systems were tested for their sensitivity to infrasound: wake after sleep onset (WASO; primary outcome) and other measures of sleep physiology, wake electroencephalography, WTS symptoms, cardiovascular physiology, and neurobehavioral performance. RESULTS: We randomized 37 noise-sensitive but otherwise healthy adults (18-72 years of age; 51% female) into the study before a COVID19-related public health order forced the study to close. WASO was not affected by infrasound compared with sham infrasound (-1.36 min; 95% CI: -6.60, 3.88, p=0.60) but was worsened by the active control traffic exposure compared with sham by 6.07 min (95% CI: 0.75, 11.39, p=0.02). Infrasound did not worsen any subjective or objective measures used. DISCUSSION: Our findings did not support the idea that infrasound causes WTS. High level, but inaudible, infrasound did not appear to perturb any physiological or psychological measure tested in these study participants. https://doi.org/10.1289/EHP10757.

The Effect of Light Therapy on Electroencephalographic Sleep in Sleep and Circadian Rhythm Disorders: A Scoping Review.

Light therapy is used to treat sleep and circadian rhythm disorders, yet there are limited studies on whether light therapy impacts electroencephalographic (EEG) activity during sleep. Therefore, we aimed to provide an overview of research studies that examined the effects of light therapy on sleep macro- and micro-architecture in populations with sleep and circadian rhythm disorders. We searched for randomized controlled trials that used light therapy and included EEG sleep measures using MEDLINE, PubMed, CINAHL, PsycINFO and Cochrane Central Register of Controlled Trials databases. Five articles met the inclusion criteria of patients with either insomnia or delayed sleep−wake phase disorder (DSWPD). These trials reported sleep macro-architecture outcomes using EEG or polysomnography. Three insomnia trials showed no effect of the timing or intensity of light therapy on total sleep time, wake after sleep onset, sleep efficiency and sleep stage duration compared to controls. Only one insomnia trial reported significantly higher sleep efficiency after evening light therapy (>4000 lx between 21:00−23:00 h) compared with afternoon light therapy (>4000 lx between 15:00−17:00 h). In the only DSWPD trial, six multiple sleep latency tests were conducted across the day (09:00 and 19:00 h) and bright light (2500 lx) significantly lengthened sleep latency in the morning (09:00 and 11:00 h) compared to control light (300 lx). None of the five trials reported any sleep micro-architecture measures. Overall, there was limited research about the effect of light therapy on EEG sleep measures, and studies were confined to patients with insomnia and DSWPD only. More research is needed to better understand whether lighting interventions in clinical populations affect sleep macro- and micro-architecture and objective sleep timing and quality.

A systematic scoping review of the effects of central nervous system active drugs on sleep spindles and sleep-dependent memory consolidation.

Sleep spindles are key electroencephalogram (EEG) oscillatory events that occur during non-rapid eye movement (NREM) sleep. Deficits in sleep spindles are present in populations with sleep and neurological disorders, and in severe mental illness. Pharmacological manipulation of these waveforms is of growing interest with therapeutic potential in targeting spindle deficits relating to memory impairment. This review integrates studies that provide insight into the feasibility of manipulating sleep spindles by using psychoactive drug classes, with consequent effects on sleep-dependent memory. Most studies showed that benzodiazepines and Z-drugs consistently enhanced sleep spindle activity unlike other psychoactive drug classes reviewed. However, how these spindle enhancements translate into improved sleep-dependent memory remains to be fully elucidated. From the few studies that examined both spindles and memory, preliminary evidence suggests that zolpidem may have some therapeutic potential to enhance declarative memory through boosting sleep spindle activity. There is a greater need to standardise methodological approaches for identifying and quantifying spindle activity as well as more exploratory studies to elucidate the role of spindle enhancement for other types of memory.

The association between sleep microarchitecture and cognitive function in middle-aged and older men: a community-based cohort study.

STUDY OBJECTIVES: Sleep microarchitecture parameters determined by quantitative power spectral analysis of electroencephalograms have been proposed as potential brain-specific markers of cognitive dysfunction. However, data from community samples remain limited. This study examined cross-sectional associations between sleep microarchitecture and cognitive dysfunction in community-dwelling men. METHODS: Florey Adelaide Male Ageing Study participants (n = 477) underwent home-based polysomnography (2010-2011). All-night electroencephalogram recordings were processed using quantitative power spectral analysis following artifact exclusion. Cognitive testing (2007-2010) included the inspection time task, Trail-Making Tests A and B, and Fuld object memory evaluation. Complete case cognition, polysomnography, and covariate data were available in 366 men. Multivariable linear regression models controlling for demographic, biomedical, and behavioral confounders determined cross-sectional associations between sleep microarchitecture and cognitive dysfunction overall and by age-stratified subgroups. RESULTS: In the overall sample, worse Trail-Making Test A performance was associated with higher rapid eye movement (REM) theta and alpha and non-REM theta but lower delta power (all P < .05). In men ≥ 65 years, worse Trail-Making Test A performance was associated with lower non-REM delta but higher non-REM and REM theta and alpha power (all P < .05). Furthermore, in men ≥ 65 years, worse Trail-Making Test B performance was associated with lower REM delta but higher theta and alpha power (all P < .05). CONCLUSIONS: Sleep microarchitecture parameters may represent important brain-specific markers of cognitive dysfunction, particularly in older community-dwelling men. Therefore, this study extends the emerging community-based cohort literature on a potentially important link between sleep microarchitecture and cognitive dysfunction. The utility of sleep microarchitecture for predicting prospective cognitive dysfunction and decline warrants further investigation. CITATION: Parker JL, Appleton SL, Melaku YA, et al. The association between sleep microarchitecture and cognitive function in middle-aged and older men: a community-based cohort study. J Clin Sleep Med. 2022;18(6):1593-1608.

Improvements in cognitive function and quantitative sleep electroencephalogram in obstructive sleep apnea after six months of continuous positive airway pressure treatment.

STUDY OBJECTIVES: Untreated obstructive sleep apnea (OSA) is associated with cognitive deficits and altered brain electrophysiology. We evaluated the effect of continuous positive airway pressure (CPAP) treatment on quantitative sleep electroencephalogram (EEG) measures and cognitive function. METHODS: We studied 167 patients with OSA (age 50 ±â€…13, AHI 35.0 ±â€…26.8) before and after 6 months of CPAP. Cognitive tests assessed working memory, sustained attention, visuospatial scanning, and executive function. All participants underwent overnight polysomnography at baseline and after CPAP. Power spectral analysis was performed on EEG data (C3-M2) in a sub-set of 90 participants. Relative delta EEG power and sigma power in NREM and EEG slowing in REM were calculated. Spindle densities (events/min) in N2 were also derived using automated spindle event detection. All outcomes were analysed as change from baseline. RESULTS: Cognitive function across all cognitive domains improved after six months of CPAP. In our sub-set, increased relative delta power (p < .0001) and reduced sigma power (p = .001) during NREM were observed after the 6-month treatment period. Overall, fast and slow sleep spindle densities during N2 were increased after treatment. CONCLUSIONS: Cognitive performance was improved and sleep EEG features were enhanced when assessing the effects of CPAP. These findings suggest the reversibility of cognitive deficits and altered brain electrophysiology observed in untreated OSA following six months of treatment.

The association between obstructive sleep apnea and sleep spindles in middle-aged and older men: a community-based cohort study.

STUDY OBJECTIVES: Sleep spindles show morphological changes in obstructive sleep apnea (OSA). However, previous small studies have limited generalizability, leaving associations between OSA severity measures and spindle metrics uncertain. This study examined cross-sectional associations between OSA severity measures and spindle metrics among a large population-based sample of men. METHODS: Community-dwelling men with no previous OSA diagnosis underwent home-based polysomnography. All-night EEG (F4-M1) recordings were processed for artifacts and spindle events identified using previously validated algorithms. Spindle metrics of interest included frequency (Hz), amplitude (µV2), overall density (11-16 Hz), slow density (11-13 Hz), and fast density (13-16 Hz) (number/minute). Multivariable linear regression models controlling for demographic, biomedical, and behavioral confounders were used to examine cross-sectional associations between OSA severity measures and spindle metrics. RESULTS: In adjusted analyses, higher apnea-hypopnea index (AHI/h, as a continuous variable) and percentage total sleep time with oxygen saturation <90% (TST90) were associated with decreased slow spindle density (AHI, B = -0.003, p = 0.032; TST90, B = -0.004, p = 0.047) but increased frequency (AHI, B = 0.002, p = 0.009; TST90, B = 0.002, p = 0.043). Higher TST90 was also associated with greater spindle amplitude (N2 sleep, B = 0.04, p = 0.011; N3 sleep, B = 0.11, p < 0.001). Furthermore, higher arousal index was associated with greater spindle amplitude during N2 sleep (B = 0.31, p < 0.001) but decreased overall density (B = -1.27, p = 0.030) and fast density (B = -4.36, p = 0.028) during N3 sleep. CONCLUSIONS: Among this large population-based sample of men, OSA severity measures were independently associated with spindle abnormalities. Further population studies are needed to determine associations between spindle metrics and functional outcomes.