A multidimensional investigation of sleep and biopsychosocialprofiles with associated neural signatures.

Sleep is essential for optimal functioning and health. Interconnected to multiple biological, psychological and socio-environmental factors (i.e., biopsychosocial factors), the multidimensional nature of sleep is rarely capitalized on in research. Here, we deployed a data-driven approach to identify sleep-biopsychosocial profiles that linked self-reported sleep patterns to inter-individual variability in health, cognition, and lifestyle factors in 770 healthy young adults. We uncovered five profiles, including two profiles reflecting general psychopathology associated with either reports of general poor sleep or an absence of sleep complaints (i.e., sleep resilience) respectively. The three other profiles were driven by sedative-hypnotics-use and social satisfaction, sleep duration and cognitive performance, and sleep disturbance linked to cognition and mental health. Furthermore, identified sleep-biopsychosocial profiles displayed unique patterns of brain network organization. In particular, somatomotor network connectivity alterations were involved in the relationships between sleep and biopsychosocial factors. These profiles can potentially untangle the interplay between individuals' variability in sleep, health, cognition and lifestyle - equipping research and clinical settings to better support individual's well-being.

A multidimensional investigation of sleep and biopsychosocial profiles with associated neural signatures.

Sleep is essential for optimal functioning and health. Interconnected to multiple biological, psychological and socio-environmental factors (i.e., biopsychosocial factors), the multidimensional nature of sleep is rarely capitalized on in research. Here, we deployed a data-driven approach to identify sleep-biopsychosocial profiles that linked self-reported sleep patterns to inter-individual variability in health, cognition, and lifestyle factors in 770 healthy young adults. We uncovered five profiles, including two profiles reflecting general psychopathology associated with either reports of general poor sleep or an absence of sleep complaints (i.e., sleep resilience) respectively. The three other profiles were driven by sedative-hypnotics-use and social satisfaction, sleep duration and cognitive performance, and sleep disturbance linked to cognition and mental health. Furthermore, identified sleep-biopsychosocial profiles displayed unique patterns of brain network organization. In particular, somatomotor network connectivity alterations were involved in the relationships between sleep and biopsychosocial factors. These profiles can potentially untangle the interplay between individuals' variability in sleep, health, cognition and lifestyle - equipping research and clinical settings to better support individual's well-being.

Methodological approach to sleep state misperception in insomnia disorder: Comparison between multiple nights of actigraphy recordings and a single night of polysomnography recording.

STUDY OBJECTIVE: To provide a comprehensive assessment of sleep state misperception in insomnia disorder (INS) and good sleepers (GS) by comparing recordings performed for one night in-lab (PSG and night review) and during several nights at-home (actigraphy and sleep diaries). METHODS: Fifty-seven INS and 29 GS wore an actigraphy device and filled a sleep diary for two weeks at-home. They subsequently completed a PSG recording and filled a night review in-lab. Sleep perception index (subjective/objective × 100) of sleep onset latency (SOL), sleep duration (TST) and wake duration (TST) were computed and compared between methods and groups. RESULTS: GS displayed a tendency to overestimate TST and WASO but correctly perceived SOL. The degree of misperception was similar across methods within the GS group. In contrast, INS underestimated their TST and overestimated their SOL both in-lab and at-home, yet the severity of misperception of SOL was larger at-home than in-lab. Finally, INS overestimated WASO only in-lab while correctly perceiving it at-home. While only the degree of TST misperception was stable across methods in INS, misperception of SOL and WASO were dependent on the method used. CONCLUSIONS: We found that GS and INS exhibit opposite patterns and severity of sleep misperception. While the degree of misperception in GS was similar across methods, only sleep duration misperception was reliably detected by both in-lab and at-home methods in INS. Our results highlight that, when assessing sleep misperception in insomnia disorder, the environment and method of data collection should be carefully considered.

Slow oscillation-spindle cross-frequency coupling predicts overnight declarative memory consolidation in older adults.

Cross-frequency coupling (CFC) between brain oscillations during non-rapid-eye-movement (NREM) sleep (e.g. slow oscillations [SO] and spindles) may be a neural mechanism of overnight memory consolidation. Declines in CFC across the lifespan might accompany coinciding memory problems with ageing. However, there are few reports of CFC changes during sleep after learning in older adults, controlling for baseline effects. Our objective was to examine NREM CFC in healthy older adults, with an emphasis on spindle activity and SOs from frontal electroencephalogram (EEG), during a learning night after a declarative learning task, as compared to a baseline night without learning. Twenty-five older adults (M [SD] age = 69.12 [5.53] years; 64% female) completed a two-night study, with a pre- and post-sleep word-pair associates task completed on the second night. SO-spindle coupling strength and a measure of coupling phase distance from the SO up-state were both examined for between-night differences and associations with memory consolidation. Coupling strength and phase distance from the up-state peak were both stable between nights. Change in coupling strength between nights was not associated with memory consolidation, but a shift in coupling phase towards (vs. away from) the up-state peak after learning predicted better memory consolidation. Also, an exploratory interaction model suggested that associations between coupling phase closer to the up-state peak and memory consolidation may be moderated by higher (vs. lower) coupling strength. This study supports a role for NREM CFC in sleep-related memory consolidation in older adults.

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.

Effects of cognitive behavioral therapy for insomnia on subjective and objective measures of sleep and cognition.

STUDY OBJECTIVES: To assess the effects of Cognitive Behavioral Therapy for insomnia (CBTi) on subjective and objective measures of sleep, sleep-state misperception and cognitive performance. METHODS: We performed a randomized-controlled trial with a treatment group and a wait-list control group to assess changes in insomnia symptoms after CBTi (8 weekly group sessions/3 months) in 62 participants with chronic insomnia. To this end, we conducted a multimodal investigation of sleep and cognition including subjective measures of sleep difficulties (Insomnia Severity Index [ISI]; sleep diaries) and cognitive functioning (Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire), objective assessments of sleep (polysomnography recording), cognition (attention and working memory tasks), and sleep-state misperception measures, collected at baseline and at 3-months post-randomization. We also assessed ISI one year after CBTi. Our main analysis investigated changes in sleep and cognition after 3 months (treatment versus wait-list). RESULTS: While insomnia severity decreased and self-reported sleep satisfaction improved after CBTi, we did not find any significant change in objective and subjective sleep measures (e.g., latency, duration). Degree of discrepancy between subjective and objective sleep (i.e., sleep misperception) in sleep latency and sleep duration decreased after CBTi suggesting a better perception of sleep after CBTi. In contrast, both objective and subjective cognitive functioning did not improve after CBTi. CONCLUSIONS: We showed that group-CBTi has a beneficial effect on variables pertaining to the subjective perception of sleep, which is a central feature of insomnia. However, we observed no effect of CBTi on measures of cognitive functioning.

An altered balance of integrated and segregated brain activity is a marker of cognitive deficits following sleep deprivation.

Sleep deprivation (SD) leads to impairments in cognitive function. Here, we tested the hypothesis that cognitive changes in the sleep-deprived brain can be explained by information processing within and between large-scale cortical networks. We acquired functional magnetic resonance imaging (fMRI) scans of 20 healthy volunteers during attention and executive tasks following a regular night of sleep, a night of SD, and a recovery nap containing nonrapid eye movement (NREM) sleep. Overall, SD was associated with increased cortex-wide functional integration, driven by a rise of integration within cortical networks. The ratio of within versus between network integration in the cortex increased further in the recovery nap, suggesting that prolonged wakefulness drives the cortex towards a state resembling sleep. This balance of integration and segregation in the sleep-deprived state was tightly associated with deficits in cognitive performance. This was a distinct and better marker of cognitive impairment than conventional indicators of homeostatic sleep pressure, as well as the pronounced thalamocortical connectivity changes that occurs towards falling asleep. Importantly, restoration of the balance between segregation and integration of cortical activity was also related to performance recovery after the nap, demonstrating a bidirectional effect. These results demonstrate that intra- and interindividual differences in cortical network integration and segregation during task performance may play a critical role in vulnerability to cognitive impairment in the sleep-deprived state.

More than a quarter century of the most prescribed sleeping pill: Systematic review of zolpidem use by older adults.

Zolpidem is widely used to treat insomnia of older adults despite that few randomized controlled studies were conducted in this group. We systematically reviewed the relevant literature on efficacy/effectiveness and safety of zolpidem use by elderly individuals in relevant databases completed with a manual search of key journals. Studies were required to include individuals aged ≥60 years under intervention with zolpidem compared to placebo or other hypnosedatives. Outcomes were either objectively- or subjectively-assessed improvements in specific sleep parameters and safety for clinical use. The 31 reports selected for review were mostly of low-quality. The evidence suggests that zolpidem is useful typically by reducing sleep latency and episodes of wake after sleep onset, and increasing total sleep time and sleep efficiency. Regarding safety and tolerability, analyses suggest a low risk of daytime sleepiness and of deleterious effects on memory or psychomotor performance, provided that recommended dosage and precautions are followed. Few retrospective studies associate zolpidem use with risk of falls, fractures, dementia, cancer, and stroke. Zolpidem appears effective at lower doses and for short-term treatment among the elderly. Rigorous, new clinical trials are warranted to further document the specific effects of zolpidem in older individuals.

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

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.

Structural brain correlates of obstructive sleep apnoea in older adults at risk for dementia.

This study aimed to investigate associations between obstructive sleep apnoea (OSA) and cortical thickness in older adults with subjective and objective cognitive difficulties, who are considered "at-risk" for dementia.83 middle-aged to older adults (51-88 years) underwent neuropsychological testing, polysomnography assessment of OSA and a structural magnetic resonance imaging brain scan. A principal components analysis was performed on OSA measures. Cortical thickness and subcortical volumes were compared to extracted components of "oxygen desaturation" and "sleep disturbance".Oxygen desaturation was significantly related to reduced cortical thickness in the bilateral temporal lobes (left: r=-0.44, p<0.001; right: r=-0.39, p=0.003). Conversely, sleep disturbance was associated with increased thickness in the right postcentral gyrus (r=0.48, p<0.001), pericalcarine (r=0.50, p=0.005) and pars opercularis (r=0.46, p=0.009) and increased volume of the hippocampus and amygdala. Decreased thickness in the bilateral temporal regions was associated with reduced verbal encoding (r=0.28, p=0.010).Given the clinical significance of this sample in terms of dementia prevention, these changes in grey matter reveal how OSA might contribute to neurodegenerative processes in older adults.

Quantitative electroencephalogram measures in adult obstructive sleep apnea - Potential biomarkers of neurobehavioural functioning.

Obstructive sleep apnea (OSA) results in significantly impaired cognitive functioning and increased daytime sleepiness in some patients leading to increased risk of motor vehicle and workplace accidents and reduced productivity. Clinicians often face difficulty in identifying which patients are at risk of neurobehavioural dysfunction due to wide inter-individual variability, and disparity between symptoms and conventional metrics of disease severity such as the apnea hypopnea index. Quantitative electroencephalogram (EEG) measures are determinants of awake neurobehavioural function in healthy subjects. However, the potential value of quantitative EEG (qEEG) measurements as biomarkers of neurobehavioural function in patients with OSA has not been examined. This review summarises the existing literature examining qEEG in OSA patients including changes in brain activity during wake and sleep states, in relation to daytime sleepiness, cognitive impairment and OSA treatment. It will speculate on the mechanisms which may underlie changes in EEG activity and discuss the potential utility of qEEG as a clinically useful predictor of neurobehavioural function in OSA.

Time Trends in the Family Physician Management of Insomnia: The Australian Experience (2000-2015).

STUDY OBJECTIVES: To evaluate changes in rates of family physician (FP) management of insomnia in Australia from 2000-2015. METHODS: The Bettering the Evaluation And Care of Health (BEACH) program is a nationally representative cross-sectional survey of 1,000 newly randomly sampled family physicians' activity in Australia per year, who each record details of 100 consecutive patient encounters. This provided records of approximately 100,000 encounters each year. We identified all encounters with patients older than 15 years where insomnia or difficulty sleeping was managed and assessed trends in these encounters from 2000-2015. RESULTS: There was no change in the management rate of insomnia from 2000-2007 (1.54 per 100 encounters [95% confidence interval [CI]: 1.49-1.58]). This rate was lower from 2008-2015 (1.31 per 100 encounters [95% CI: 1.27-1.35]). There was no change in FP management: pharmacotherapy was used in approximately 90% of encounters; nonpharmacological advice was given at approximately 20%; and onward referral at approximately 1% of encounters. Prescription of temazepam changed from 54.6 [95% CI: 51.4-57.9] per 100 insomnia problems in 2000-2001 to 43.6 [95% CI: 40.1-47.0] in 2014-2015, whereas zolpidem increased steadily from introduction in 2000 to 14.6 [95% CI: 12.2-17.1] per 100 insomnia problems in 2006-2007, and then decreased to 7.3 [95% CI: 5.4-9.2] by 2014-2015. CONCLUSIONS: Insomnia management frequency decreased after 2007 in conjunction with ecologically associated Australian media reporting of adverse effects linked to zolpidem use. Australian FPs remain reliant on pharmacotherapy for the management of insomnia.

Functional Connectivity in the Default Mode Network is Reduced in Association with Nocturnal Awakening in Mild Cognitive Impairment.

BACKGROUND: Sleep disturbance is prevalent in MCI, and is a risk factor for cognitive deterioration. OBJECTIVE: To identify functional connectivity deficits in the default mode network (DMN) in patients with mild cognitive impairment (MCI) and sleep disturbance, relative to MCIs with intact sleep. METHODS: Participants comprised 47 adults aged 55 years and over, recruited from the Healthy Brain Ageing Clinic at the Brain and Mind Centre, Sydney, Australia. This sample contained 15 controls and 32 participants meeting criteria for MCI. Participants underwent resting-state fMRI and actigraphy, along with comprehensive neuropsychological, medical and psychiatric assessment. MCIs were split into two groups according to average wake after sleep onset (WASO) per night. WASO equal to or greater than 1 standard deviation (SD) above the control mean was deemed to reflect disturbed sleep. There were 11 patients in the MCI sleep-disturbed group, and 21 in the MCI sleep-intact group. RESULTS: Relative to controls, MCIs demonstrated significant connectivity reductions between parietal and temporoparietal regions, and between temporal regions. Relative to MCIs with intact sleep, MCIs with sleep disturbance demonstrated reductions in functional connectivity between temporal and parietal regions, and between temporal and temporoparietal regions. CONCLUSIONS: MCIs with nocturnal awakenings demonstrate reductions in DMN connectivity. These reductions comprise brain regions that are crucially involved in sleep and memory processes. These results strengthen our previous findings, which found reduced connectivity in MCIs with self-reported sleep disturbances. Future studies may build on these findings through incorporating complementary neuroimaging techniques and experimental manipulations of sleep.

Management of Snoring and Sleep Apnea in Australian Primary Care: The BEACH Study (2000-2014).

STUDY OBJECTIVES: To characterize the changes in management of snoring and obstructive sleep apnea (OSA) in general practice in Australia. METHODS: The Bettering the Evaluation And Care of Health (BEACH) study is a nationally representative rolling cross-sectional survey of general practice activity in Australia. We analyzed all adult (age 18+ y) encounters for OSA or snoring, annually from 2000 to 2014 (approximately 1,000 general practitioners (GPs) per year recording approximately 100,000 patient encounters per year). RESULTS: The management rate of OSA rose from 94 to 296 per 100,000 encounters, whereas management rate of snoring remained steady at approximately 15 to 25 per 100,000 encounters. The majority of patients managed for OSA were: middle-aged (25-64 y; 71.3% of all patients); overweight (90%); male (62%), although there was a trend for an increase in the proportion being female over the study period (21 to 37 per 100 encounters). Referral rates were high for both OSA (59 per 100 problems managed) and snoring (69 per 100), although medical referrals (to a sleep clinic or respiratory physician) were significantly higher for patients managed for OSA than for snoring (90% vs. 60% of all referrals). Surgical referrals were higher for snoring than for OSA (37% vs. 3% of all referrals). CONCLUSIONS: The management rate for OSA tripled from 2000 to 2014, while the rate for snoring remained steady. GPs significantly relied on the advice of other health professionals to manage OSA; however, their referral patterns aligned with what most specialists would recommend. COMMENTARY: A commentary on this article appears in this issue on page 1081.

Sleep quality in healthy older people: relationship with ¹H magnetic resonance spectroscopy markers of glial and neuronal integrity.

The hippocampus and thalamus assume a significant role in the overnight consolidation of memories, a process that is negatively impacted by sleep disruption. Emerging evidence suggests that disturbances of sleep in older people may co-occur with underlying neurobiological changes. This study sought to assess glial and neuronal integrity in these regions in relation to subjective sleep disturbance in a healthy older sample. Forty-three healthy older people (mean age = 70, SD = 5.0) were assessed clinically and medically and screened for cognitive and depressive symptoms, as well as sleep disturbance. Single voxel hippocampal and thalamus metabolite ratios of N-acetyl aspartate (NAA) and myo-inositol (mI) with total creatine (Cr + PCr) were measured using magnetic resonance spectroscopy at 3-Tesla. Higher hippocampal mI/Cr + PCr ratios were significantly correlated with poorer self-reported sleep quality (r = .42, p < .01) and less sleep efficiency (r = -0.42, p < .01) as recorded by the Pittsburgh Sleep Quality Index (Buysse, Reynolds, Monk, Berman, & Kupfer, 1989). No other significant correlations were observed within the hippocampus or within the thalamus. These results indicate that in healthy older people, subjective sleep disturbance may be associated with glial alterations in the hippocampus. Future research is now needed to examine these associations with respect to objective sleep measures and overnight memory consolidation.