A role for the serotonin 2A receptor in the expansion and functioning of human transmodal cortex.

Integrating independent but converging lines of research on brain function and neurodevelopment across scales, this article proposes that serotonin 2A receptor (5-HT2AR) signalling is an evolutionary and developmental driver and potent modulator of the macroscale functional organization of the human cerebral cortex. A wealth of evidence indicates that the anatomical and functional organization of the cortex follows a unimodal-to-transmodal gradient. Situated at the apex of this processing hierarchy-where it plays a central role in the integrative processes underpinning complex, human-defining cognition-the transmodal cortex has disproportionately expanded across human development and evolution. Notably, the adult human transmodal cortex is especially rich in 5-HT2AR expression and recent evidence suggests that, during early brain development, 5-HT2AR signalling on neural progenitor cells stimulates their proliferation-a critical process for evolutionarily-relevant cortical expansion. Drawing on multimodal neuroimaging and cross-species investigations, we argue that, by contributing to the expansion of the human cortex and being prevalent at the apex of its hierarchy in the adult brain, 5-HT2AR signalling plays a major role in both human cortical expansion and functioning. Owing to its unique excitatory and downstream cellular effects, neuronal 5-HT2AR agonism promotes neuroplasticity, learning and cognitive and psychological flexibility in a context-(hyper)sensitive manner with therapeutic potential. Overall, we delineate a dual role of 5-HT2ARs in enabling both the expansion and modulation of the human transmodal cortex.

Device-measured physical activity and cardiometabolic health: the Prospective Physical Activity, Sitting, and Sleep (ProPASS) consortium.

BACKGROUND AND AIMS: Physical inactivity, sedentary behaviour (SB), and inadequate sleep are key behavioural risk factors of cardiometabolic diseases. Each behaviour is mainly considered in isolation, despite clear behavioural and biological interdependencies. The aim of this study was to investigate associations of five-part movement compositions with adiposity and cardiometabolic biomarkers. METHODS: Cross-sectional data from six studies (n = 15 253 participants; five countries) from the Prospective Physical Activity, Sitting and Sleep consortium were analysed. Device-measured time spent in sleep, SB, standing, light-intensity physical activity (LIPA), and moderate-vigorous physical activity (MVPA) made up the composition. Outcomes included body mass index (BMI), waist circumference, HDL cholesterol, total:HDL cholesterol ratio, triglycerides, and glycated haemoglobin (HbA1c). Compositional linear regression examined associations between compositions and outcomes, including modelling time reallocation between behaviours. RESULTS: The average daily composition of the sample (age: 53.7 ± 9.7 years; 54.7% female) was 7.7 h sleeping, 10.4 h sedentary, 3.1 h standing, 1.5 h LIPA, and 1.3 h MVPA. A greater MVPA proportion and smaller SB proportion were associated with better outcomes. Reallocating time from SB, standing, LIPA, or sleep into MVPA resulted in better scores across all outcomes. For example, replacing 30 min of SB, sleep, standing, or LIPA with MVPA was associated with -0.63 (95% confidence interval -0.48, -0.79), -0.43 (-0.25, -0.59), -0.40 (-0.25, -0.56), and -0.15 (0.05, -0.34) kg/m2 lower BMI, respectively. Greater relative standing time was beneficial, whereas sleep had a detrimental association when replacing LIPA/MVPA and positive association when replacing SB. The minimal displacement of any behaviour into MVPA for improved cardiometabolic health ranged from 3.8 (HbA1c) to 12.7 (triglycerides) min/day. CONCLUSIONS: Compositional data analyses revealed a distinct hierarchy of behaviours. Moderate-vigorous physical activity demonstrated the strongest, most time-efficient protective associations with cardiometabolic outcomes. Theoretical benefits from reallocating SB into sleep, standing, or LIPA required substantial changes in daily activity.

Relationship of device measured physical activity type and posture with cardiometabolic health markers: pooled dose-response associations from the Prospective Physical Activity, Sitting and Sleep Consortium.

AIMS/HYPOTHESIS: The aim of this study was to examine the dose-response associations of device-measured physical activity types and postures (sitting and standing time) with cardiometabolic health. METHODS: We conducted an individual participant harmonised meta-analysis of 12,095 adults (mean ± SD age 54.5±9.6 years; female participants 54.8%) from six cohorts with thigh-worn accelerometry data from the Prospective Physical Activity, Sitting and Sleep (ProPASS) Consortium. Associations of daily walking, stair climbing, running, standing and sitting time with a composite cardiometabolic health score (based on standardised z scores) and individual cardiometabolic markers (BMI, waist circumference, triglycerides, HDL-cholesterol, HbA1c and total cholesterol) were examined cross-sectionally using generalised linear modelling and cubic splines. RESULTS: We observed more favourable composite cardiometabolic health (i.e. z score <0) with approximately 64 min/day walking (z score [95% CI] -0.14 [-0.25, -0.02]) and 5 min/day stair climbing (-0.14 [-0.24, -0.03]). We observed an equivalent magnitude of association at 2.6 h/day standing. Any amount of running was associated with better composite cardiometabolic health. We did not observe an upper limit to the magnitude of the dose-response associations for any activity type or standing. There was an inverse dose-response association between sitting time and composite cardiometabolic health that became markedly less favourable when daily durations exceeded 12.1 h/day. Associations for sitting time were no longer significant after excluding participants with prevalent CVD or medication use. The dose-response pattern was generally consistent between activity and posture types and individual cardiometabolic health markers. CONCLUSIONS/INTERPRETATION: In this first activity type-specific analysis of device-based physical activity, ~64 min/day of walking and ~5.0 min/day of stair climbing were associated with a favourable cardiometabolic risk profile. The deleterious associations of sitting time were fully attenuated after exclusion of participants with prevalent CVD and medication use. Our findings on cardiometabolic health and durations of different activities of daily living and posture may guide future interventions involving lifestyle modification.

Joint associations of diet and physical activity with incident type 2 diabetes and hypertension: an analysis of 144,288 UK Biobank participants.

BACKGROUND: Studies examining the joint associations of lifestyle exposures can reveal novel synergistic and joint effects, but no study has examined the joint association of diet and physical activity (PA) with type 2 diabetes (T2D) and hypertension. The aim of this study is to examine the joint associations of PA and diet with incidence of type T2D and hypertension, as a combined outcome and separately in a large sample of UK adults. METHODS: This prospective cohort study included 144,288 UK Biobank participants aged 40-69. Moderate to vigorous PA (MVPA) was measured using the International Physical Activity Questionnaire and a wrist accelerometer. We categorised PA and diet indicators (diet quality score (DQS) and energy intake (EI)) based on tertiles and derived joint PA and diet variables. Outcome was major cardiometabolic disease incidence (combination of T2D and hypertension). RESULTS: A total of 14,003(7.1%) participants developed T2D, 28,075(19.2%) developed hypertension, and 30,529(21.2%) developed T2D or hypertension over a mean follow-up of 10.9(3.7) years. Participants with middle and high self-reported MVPA levels had lower risk of major cardiometabolic disease regardless of diet, e.g. among high DQS group, hazard ratios in middle and high MVPA group were 0.90 (95%CI:0.86-0.94), and 0.88(95%CI:0.84-0.92), respectively. Participants with jointly high device-measured MVPA and high DQS levels had lower major cardiometabolic disease risk (HR: 0.84, 95%CI:0.71-0.99). The equivalent joint device-measured MVPA and EI exposure analyses showed no clear pattern of associations with the outcomes. CONCLUSION: Higher PA is an important component in cardiometabolic disease prevention across all diet quality and total EI groups. The observed lack of association between diet health outcomes may stem from a lower DQS.

Contribution of Nutritional, Lifestyle, and Metabolic Risk Factors to Parkinson's Disease.

BACKGROUND: Modifiable risk factors for Parkinson's disease (PD) are poorly known. OBJECTIVES: The aim is to evaluate independent associations of different nutritional components, physical activity, and sedentary behavior and metabolic factors with the risk of PD. METHODS: In this population-based prospective cohort study using the data of the United Kingdom Biobank (from 2006-2010), 502,017 men and women who were free from PD (International Classification of Diseases 10th edition; "G20") at baseline were included. We implemented a Cox proportion hazard's model to evaluate the associations of different levels of physical activity, sitting time, sleep habits, diet quality, alcohol and coffee consumption, smoking, and body mass index with PD risk, adjusting for several confounding variables. RESULTS: During a median follow-up of 12.8 years, lifestyle factors including vigorous physical activity (hazard ration [HR] = 0.84; 95% confidence interval [CI], 0.75-0.94), low-to-moderate sitting time (HR = 0.89; 95% CI, 0.81-0.97), and high sleep quality (HR = 0.89; 95% CI, 0.80-0.99) were associated with a reduced risk of PD. Small amounts of coffee (HR = 0.88; 95% CI, 0.82-0.95), red meat (HR = 0.86; 95% CI, 0.76-0.97), and current smoking (HR = 0.65; 95% CI, 0.56-0.75) were also associated with a lower risk of PD, whereas alcohol intake (HR = 1.29; 95% CI, 1.06-1.56) with higher PD risk. Secondary analysis, including metabolic risk factors, confirmed these findings and highlighted the potential protective effect of plasma vitamin D and uric acid, but of low-density lipoprotein-cholesterol, triglycerides, and C-reactive protein as well. CONCLUSIONS: Vigorous physical activity, reduced sitting time, good sleep quality together with small coffee intake and vitamin D supplementation are potentially neuroprotective lifestyle interventions for the prevention of PD. © 2024 International Parkinson and Movement Disorder Society.

Device-measured sedentary time and intensity-specific physical activity in relation to all-cause and cardiovascular disease mortality: the UK Biobank cohort study.

BACKGROUND AND AIMS: Understanding the amounts of intensity-specific movement needed to attenuate the association between sedentary time and mortality may help to inform personalized prescription and behavioral counselling. Herein, we examined the joint associations of sedentary time and intensity-specific physical activity with all-cause and cardiovascular disease (CVD) mortality. METHODS: Prospective cohort study including 73,729 adults from the UK Biobank who wore an Axivity AX3 accelerometer on their dominant wrist for at least 3 days, being one a weekend day, between June 2013 and December 2015. We considered the median tertile values of sedentary time and physical activity in each intensity band to determine the amount of physical activity needed to attenuate the association between sedentary time and mortality. RESULTS: During a median of 6.9 years of follow-up (628,807 person-years), we documented 1521 deaths, including 388 from CVD. Physical activity of any intensity attenuated the detrimental association of sedentary time with mortality. Overall, at least a median of 6 min/day of vigorous physical activity, 30 min/day of MVPA, 64 min/day of moderate physical activity, or 163 min/day of light physical activity (mutually-adjusted for other intensities) attenuated the association between sedentary time and mortality. High sedentary time was associated with higher risk of CVD mortality only among participants with low MVPA (HR 1.96; 95% CI 1.23 to 3.14). CONCLUSIONS: Different amounts of each physical activity intensity may attenuate the association between high sedentary time and mortality.

A narrative review of global and national physical activity and sedentary behaviour guidelines development processes - The GUidelines Standards (GUS) project.

BACKGROUND: Clinical and public health guidelines serve to direct clinical practice and policy, based on the best available evidence. The World Health Organization (WHO) and national health bodies of many countries have released physical activity and sedentary behaviour guidelines. Despite significant overlap in the body of evidence reviewed, the guidelines differ across jurisdictions. This study aimed to review the processes used to develop global and national physical activity and sedentary behaviour guidelines and examine the extent to which they conform with a recommended methodological standard for the development of guidelines. METHODS: We extracted data on nine sets of guidelines from seven jurisdictions (WHO, Australia, Canada, Japan, the Netherlands, United Kingdom, and United States). We rated each set of guidelines as high, medium, or low quality on criteria related to the rigour of the development process. RESULTS: We observed variation in the quality of guidelines development processes across jurisdictions and across different criteria. Guidelines received the strongest overall ratings for criteria on clearly describing the evidence selected and stating an explicit link between the recommendations and the supporting evidence. Guidelines received the weakest overall ratings for criteria related to clearly describing the methods used to formulate the recommendations and reporting external review by experts prior to publication. Evaluated against the selected criteria, the strongest processes were undertaken by the WHO and Canada. CONCLUSIONS: Reaching agreement on acceptable guideline development processes, as well as the inclusion and appraisal procedures of different types of evidence, would help to strengthen and align future guidelines.

Acute thalamic connectivity precedes chronic post-concussive symptoms in mild traumatic brain injury.

Chronic post-concussive symptoms are common after mild traumatic brain injury (mTBI) and are difficult to predict or treat. Thalamic functional integrity is particularly vulnerable in mTBI and may be related to long-term outcomes but requires further investigation. We compared structural MRI and resting state functional MRI in 108 patients with a Glasgow Coma Scale (GCS) of 13-15 and normal CT, and 76 controls. We examined whether acute changes in thalamic functional connectivity were early markers for persistent symptoms and explored neurochemical associations of our findings using PET data. Of the mTBI cohort, 47% showed incomplete recovery 6 months post-injury. Despite the absence of structural changes, we found acute thalamic hyperconnectivity in mTBI, with specific vulnerabilities of individual thalamic nuclei. Acute fMRI markers differentiated those with chronic post-concussive symptoms, with time- and outcome-dependent relationships in a sub-cohort followed longitudinally. Moreover, emotional and cognitive symptoms were associated with changes in thalamic functional connectivity to known serotonergic and noradrenergic targets, respectively. Our findings suggest that chronic symptoms can have a basis in early thalamic pathophysiology. This may aid identification of patients at risk of chronic post-concussive symptoms following mTBI, provide a basis for development of new therapies and facilitate precision medicine application of these therapies.

The Effect of Using Anchored Wake Time to Derive 24-h Device Measured Circadian Physical Behavior Patterns.

INTRODUCTION: Tailoring physical activity interventions to individual chronotypes and preferences by time of day could promote more effective and sustainable behavior change; however, our understanding of circadian physical behavior patterns is very limited. OBJECTIVE: To characterize and compare 24-h physical behavior patterns expressed relative to clock time (the standard measurement of time-based on a 24-h day) versus wake-up time in a large British cohort age 46. METHODS: Data were analyzed from 4979 participants in the age 46 sweep of the 1970 British Cohort Study who had valid activPAL accelerometer data across ≥4 days. Average steps and upright time (time standing plus time stepping) per 30-min interval were determined for weekdays and weekends, both in clock time and synchronized to individual wake-up times. RESULTS: The mean weekday steps were 9588, and the mean weekend steps were 9354. The mean weekday upright time was 6.6 h, and the mean weekend upright time was 6.4 h. When synchronized to wake-up time, steps peaked 1 h after waking on weekdays and 2.5 h after waking on weekends. Upright time peaked immediately, in the first 30-min window, after waking on both weekdays and weekends. CONCLUSIONS: Aligning accelerometer data to wake-up times revealed distinct peaks in stepping and upright times shortly after waking. Activity built up more gradually across clock time in the mornings, especially on weekends. Synchronizing against wake-up times highlighted the importance of circadian rhythms and personal schedules in understanding population 24-h physical behavior patterns, and this may have important implications for promoting more effective and sustainable behavior change.

Feasibility and acceptability of a cohort study baseline data collection of device-measured physical behaviors and cardiometabolic health in Saudi Arabia: expanding the Prospective Physical Activity, Sitting and Sleep consortium (ProPASS) in the Middle East.

BACKGROUND: Physical behaviors such physical activity, sedentary behavior, and sleep are associated with mortality, but there is a lack of epidemiological data and knowledge using device-measured physical behaviors. PURPOSE: To assess the feasibility of baseline data collection using the Prospective Physical Activity, Sitting, and Sleep consortium (ProPASS) protocols in the specific context of Saudi Arabia. ProPASS is a recently developed global platform for collaborative research that aims to harmonize retrospective and prospective data on device-measured behaviors and health. Using ProPASS methods for collecting data to perform such studies in Saudi Arabia will provide standardized data from underrepresented countries. METHOD: This study explored the feasibility of baseline data collection in Saudi Arabia between November and December 2022 with a target recruitment of 50 participants aged ≥ 30 years. Established ProPASS methods were used to measure anthropometrics, measure blood pressure, collect blood samples, carry out physical function test, and measure health status and context of physical behaviors using questionnaires. The ActivPal™ device was used to assess physical behaviors and the participants were asked to attend two sessions at (LHRC). The feasibility of the current study was assessed by evaluating recruitment capability, acceptability, suitability of study procedures, and resources and abilities to manage and implement the study. Exit interviews were conducted with all participants. RESULT: A total of 75 participants expressed an interest in the study, out of whom 54 initially agreed to participate. Ultimately, 48 participants were recruited in the study (recruitment rate: 64%). The study completion rate was 87.5% of the recruited participants; 95% participants were satisfied with their participation in the study and 90% reported no negative feelings related to participating in the study. One participant reported experiencing moderate skin irritation related to placement of the accelerometer. Additionally, 96% of participants expressed their willingness to participate in the study again. CONCLUSION: Based on successful methodology, data collection results, and participants' acceptability, the ProPASS protocols are feasible to administer in Saudi Arabia. These findings are promising for establishing a prospective cohort in Saudi Arabia.

Dopaminergic brainstem disconnection is common to pharmacological and pathological consciousness perturbation.

Clinical research into consciousness has long focused on cortical macroscopic networks and their disruption in pathological or pharmacological consciousness perturbation. Despite demonstrating diagnostic utility in disorders of consciousness (DoC) and monitoring anesthetic depth, these cortico-centric approaches have been unable to characterize which neurochemical systems may underpin consciousness alterations. Instead, preclinical experiments have long implicated the dopaminergic ventral tegmental area (VTA) in the brainstem. Despite dopaminergic agonist efficacy in DoC patients equally pointing to dopamine, the VTA has not been studied in human perturbed consciousness. To bridge this translational gap between preclinical subcortical and clinical cortico-centric perspectives, we assessed functional connectivity changes of a histologically characterized VTA using functional MRI recordings of pharmacologically (propofol sedation) and pathologically perturbed consciousness (DoC patients). Both cohorts demonstrated VTA disconnection from the precuneus and posterior cingulate (PCu/PCC), a main default mode network node widely implicated in consciousness. Strikingly, the stronger VTA-PCu/PCC connectivity was, the more the PCu/PCC functional connectome resembled its awake configuration, suggesting a possible neuromodulatory relationship. VTA-PCu/PCC connectivity increased toward healthy control levels only in DoC patients who behaviorally improved at follow-up assessment. To test whether VTA-PCu/PCC connectivity can be affected by a dopaminergic agonist, we demonstrated in a separate set of traumatic brain injury patients without DoC that methylphenidate significantly increased this connectivity. Together, our results characterize an in vivo dopaminergic connectivity deficit common to reversible and chronic consciousness perturbation. This noninvasive assessment of the dopaminergic system bridges preclinical and clinical work, associating dopaminergic VTA function with macroscopic network alterations, thereby elucidating a critical aspect of brainstem-cortical interplay for consciousness.

Do the associations of daily steps with mortality and incident cardiovascular disease differ by sedentary time levels? A device-based cohort study.

OBJECTIVES: This study aims to examine the associations of daily step count with all-cause mortality and incident cardiovascular disease (CVD) by sedentary time levels and to determine if the minimal and optimal number of daily steps is modified by high sedentary time. METHODS: Using data from the UK Biobank, this was a prospective dose-response analysis of total daily steps across low (<10.5 hours/day) and high (≥10.5 hours/day) sedentary time (as defined by the inflection point of the adjusted absolute risk of sedentary time with the two outcomes). Mortality and incident CVD was ascertained through 31 October 2021. RESULTS: Among 72 174 participants (age=61.1±7.8 years), 1633 deaths and 6190 CVD events occurred over 6.9 (±0.8) years of follow-up. Compared with the referent 2200 steps/day (5th percentile), the optimal dose (nadir of the curve) for all-cause mortality ranged between 9000 and 10 500 steps/day for high (HR (95% CI)=0.61 (0.51 to 0.73)) and low (0.69 (0.52 to 0.92)) sedentary time. For incident CVD, there was a subtle gradient of association by sedentary time level with the lowest risk observed at approximately 9700 steps/day for high (0.79 (0.72 to 0.86)) and low (0.71 (0.61 to 0.83)) sedentary time. The minimal dose (steps/day associated with 50% of the optimal dose) of daily steps was between 4000 and 4500 steps/day across sedentary time groups for all-cause mortality and incident CVD. CONCLUSIONS: Any amount of daily steps above the referent 2200 steps/day was associated with lower mortality and incident CVD risk, for low and high sedentary time. Accruing 9000-10 500 steps/day was associated with the lowest mortality risk independent of sedentary time. For a roughly equivalent number of steps/day, the risk of incident CVD was lower for low sedentary time compared with high sedentary time.

Associations of the 'weekend warrior' physical activity pattern with all-cause, cardiovascular disease and cancer mortality: the Mexico City Prospective Study.

OBJECTIVES: The objective was to investigate the benefits of the 'weekend warrior' physical activity pattern in Latin America, where many people take part in high levels of non-exercise physical activity. METHODS: Participants in the Mexico City Prospective Study were surveyed from 1998 to 2004 and resurveyed from 2015 to 2019. Those who exercised up to once or twice per week were termed weekend warriors. Those who exercised more often were termed regularly active. Analyses were adjusted for potential confounders. RESULTS: The main analysis included 26 006 deaths in 154 882 adults (67% female) aged 52±13 years followed for 18±4 years (mean±SD). Compared with those who reported no exercise, the HR (95% CI) was 0.88 (0.83 to 0.93) in the weekend warriors and 0.88 (0.84 to 0.91) in the regularly active. Similar results were observed for cardiovascular disease and cancer mortality, but associations were weaker. Stratified analyses showed that substantial reductions in all-cause mortality risk only occurred when the duration of exercise sessions was at least 30-60 min. The repeated-measures analysis included 843 deaths in 10 023 adults followed for 20±2 years. Compared with being inactive or becoming inactive, the HR was 0.86 (95% CI 0.65 to 1.12) when being a weekend warrior or becoming a weekend warrior and 0.85 (95% CI 0.70 to 1.03) when being regularly active or becoming regularly active. CONCLUSIONS: This is the first prospective study to investigate the benefits of the weekend warrior physical activity pattern in Latin America. The results suggest that even busy adults could benefit from taking part in one or two sessions of exercise per week.

Structural disconnectivity in postoperative delirium: A perioperative two-center cohort study in older patients.

BACKGROUND: Structural disconnectivity was found to precede dementia. Global white matter abnormalities might also be associated with postoperative delirium (POD). METHODS: We recruited older patients (≥65 years) without dementia that were scheduled for major surgery. Diffusion kurtosis imaging metrics were obtained preoperatively, after 3 and 12 months postoperatively. We calculated fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), and free water (FW). A structured and validated delirium assessment was performed twice daily. RESULTS: Of 325 patients, 53 patients developed POD (16.3%). Preoperative global MD (standardized beta 0.27 [95% confidence interval [CI] 0.21-0.32] p < 0.001) was higher in patients with POD. Preoperative global MK (-0.07 [95% CI -0.11 to (-0.04)] p < 0.001) and FA (0.07 [95% CI -0.10 to (-0.04)] p < 0.001) were lower. When correcting for baseline diffusion, postoperative MD was lower after 3 months (0.05 [95% CI -0.08 to (-0.03)] p < 0.001; n = 183) and higher after 12 months (0.28 [95% CI 0.20-0.35] p < 0.001; n = 45) among patients with POD. DISCUSSION: Preoperative structural disconnectivity was associated with POD. POD might lead to white matter depletion 3 and 12 months after surgery.

Reduced emergent character of neural dynamics in patients with a disrupted connectome.

High-level brain functions are widely believed to emerge from the orchestrated activity of multiple neural systems. However, lacking a formal definition and practical quantification of emergence for experimental data, neuroscientists have been unable to empirically test this long-standing conjecture. Here we investigate this fundamental question by leveraging a recently proposed framework known as "Integrated Information Decomposition," which establishes a principled information-theoretic approach to operationalise and quantify emergence in dynamical systems - including the human brain. By analysing functional MRI data, our results show that the emergent and hierarchical character of neural dynamics is significantly diminished in chronically unresponsive patients suffering from severe brain injury. At a functional level, we demonstrate that emergence capacity is positively correlated with the extent of hierarchical organisation in brain activity. Furthermore, by combining computational approaches from network control theory and whole-brain biophysical modelling, we show that the reduced capacity for emergent and hierarchical dynamics in severely brain-injured patients can be mechanistically explained by disruptions in the patients' structural connectome. Overall, our results suggest that chronic unresponsiveness resulting from severe brain injury may be related to structural impairment of the fundamental neural infrastructures required for brain dynamics to support emergence.

Influence of poor sleep on cardiovascular disease-free life expectancy: a multi-resource-based population cohort study.

BACKGROUND: The complexity of sleep hinders the formulation of sleep guidelines. Recent studies suggest that different unhealthy sleep characteristics jointly increase the risks for cardiovascular disease (CVD). This study aimed to estimate the differences in CVD-free life expectancy between people with different sleep profiles. METHODS: We included 308,683 middle-aged adults from the UK Biobank among whom 140,181 had primary care data linkage. We used an established composite sleep score comprising self-reported chronotype, duration, insomnia complaints, snoring, and daytime sleepiness to derive three sleep categories: poor, intermediate, and healthy. We also identified three clinical sleep disorders captured by primary care and inpatient records within 2 years before enrollment in the cohort: insomnia, sleep-related breathing disorders, and other sleep disorders. We estimated sex-specific CVD-free life expectancy with three-state Markov models conditioning on survival at age 40 across different sleep profiles and clinical disorders. RESULTS: We observed a gradual loss in CVD-free life expectancy toward poor sleep such as, compared with healthy sleepers, poor sleepers lost 1.80 [95% CI 0.96-2.75] and 2.31 [1.46-3.29] CVD-free years in females and males, respectively, while intermediate sleepers lost 0.48 [0.41-0.55] and 0.55 [0.49-0.61] years. Among men, those with clinical insomnia or sleep-related breathing disorders lost CVD-free life by 3.84 [0.61-8.59] or 6.73 [5.31-8.48] years, respectively. Among women, sleep-related breathing disorders or other sleep disorders were associated with 7.32 [5.33-10.34] or 1.43 [0.20-3.29] years lost, respectively. CONCLUSIONS: Both self-reported and doctor-diagnosed poor sleep are negatively associated with CVD-free life, especially pronounced in participants with sleep-related breathing disorders.

Depressive symptoms following traumatic brain injury are associated with resting-state functional connectivity.

BACKGROUND: To determine whether depressive symptoms in traumatic brain injury (TBI) patients were associated with altered resting-state functional connectivity (rs-fc) or voxel-based morphology in brain regions involved in emotional regulation and associated with depression. METHODS: In the present study, we examined 79 patients (57 males; age range = 17-70 years, M ± s.d. = 38 ± 16.13; BDI-II, M ± s.d. = 9.84 ± 8.67) with TBI. We used structural MRI and resting-state fMRI to examine whether there was a relationship between depression, as measured with the Beck Depression Inventory (BDI-II), and the voxel-based morphology or functional connectivity in regions previously identified as involved in emotional regulation in patients following TBI. Patients were at least 4 months post-TBI (M ± s.d. = 15.13 ± 11.67 months) and the severity of the injury included mild to severe cases [Glasgow Coma Scale (GCS), M ± s.d. = 6.87 ± 3.31]. RESULTS: Our results showed that BDI-II scores were unrelated to voxel-based morphology in the examined regions. We found a positive association between depression scores and rs-fc between limbic regions and cognitive control regions. Conversely, there was a negative association between depression scores and rs-fc between limbic and frontal regions involved in emotion regulation. CONCLUSION: These findings lead to a better understanding of the exact mechanisms that contribute to depression following TBI and better inform treatment decisions.

Bidirectional associations of sleep and discretionary screen time in adults: Longitudinal analysis of the UK biobank.

The direction of the association between discretionary screen time (DST) and sleep in the adult population is largely unknown. We examined the bidirectional associations of DST and sleep patterns in a longitudinal sample of adults in the general population. A total of 31,361 UK Biobank study participants (52% female, 56.1 ± 7.5 years) had two repeated measurements of discretionary screen time (TV viewing and leisure-time computer use) and self-reported sleep patterns (five sleep health characteristics) between 2012 and 2018 (follow-up period of 6.9 ± 2.2 years). We categorised daily DST into three groups (low, <3 h/day; medium, 3-4 h/day; and high, >4 h/day), and calculated a sleep pattern composite score comprising morning chronotype, adequate sleep duration (7-8 h/day), never or rare insomnia, never or rare snoring, and infrequent daytime sleepiness. The overall sleep pattern was categorised into three groups (healthy: ≥ 4; intermediate: 2-3; and poor: ≤ 1 healthy sleep characteristic). Multiple logistic regression analyses were applied to assess associations between DST and sleep with adjustments for potential confounders. Participants with either an intermediate (OR: 1.40; 95% CI: 1.15, 1.71) or a poor (OR: 1.16; 95% CI: 1.10, 1.24) sleep pattern at baseline showed higher odds for high DST at follow-up, compared with those with a healthy baseline sleep pattern. Participants with medium (OR: 1.40; 95% CI: 1.14, 1.71) or high DST (OR: 1.62; 95% CI: 1.30, 2.00) at baseline showed higher odds for poor sleep at follow-up, compared with participants with a low DST. In conclusion, our findings provide consistent evidence that a high DST at baseline is associated with poor sleep over a nearly 7 year follow-up period, and vice versa.

Development and performance of a sleep estimation algorithm using a single accelerometer placed on the thigh: an evaluation against polysomnography.

Accelerometers placed on the thigh provide accurate measures of daily physical activity types, postures and sedentary behaviours, over 24 h and across consecutive days. However, the ability to estimate sleep duration or quality from thigh-worn accelerometers is uncertain and has not been evaluated in comparison with the 'gold-standard' measurement of sleep polysomnography. This study aimed to develop an algorithm for sleep estimation using the raw data from a thigh-worn accelerometer and to evaluate it in comparison with polysomnography. The algorithm was developed and optimised on a dataset consisting of 23 single-night polysomnography recordings, collected in a laboratory, from 15 asymptomatic adults. This optimised algorithm was then applied to a separate evaluation dataset, in which, 71 adult males (mean [SD] age 57 [11] years, height 181 [6] cm, weight 82 [13] kg) wore ambulatory polysomnography equipment and a thigh-worn accelerometer, simultaneously, whilst sleeping at home. Compared with polysomnography, the algorithm had a sensitivity of 0.84 and a specificity of 0.55 when estimating sleep periods. Sleep intervals were underestimated by 21 min (130 min, Limits of Agreement Range [LoAR]). Total sleep time was underestimated by 32 min (233 min LoAR). Our results evaluate the performance of a new algorithm for estimating sleep and outline the limitations. Based on these results, we conclude that a single device can provide estimates of the sleep interval and total sleep time with sufficient accuracy for the measurement of daily physical activity, sedentary behaviour, and sleep, on a group level in free-living settings.

The impact of selected methodological factors on data collection outcomes in observational studies of device-measured physical behaviour in adults: A systematic review.

BACKGROUND: Accelerometer measures of physical behaviours (physical activity, sedentary behaviour and sleep) in observational studies offer detailed insight into associations with health and disease. Maximising recruitment and accelerometer wear, and minimising data loss remain key challenges. How varying methods used to collect accelerometer data influence data collection outcomes is poorly understood. We examined the influence of accelerometer placement and other methodological factors on participant recruitment, adherence and data loss in observational studies of adult physical behaviours. METHODS: The review was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA). Observational studies of adults including accelerometer measurement of physical behaviours were identified using database (MEDLINE (Ovid), Embase, PsychINFO, Health Management Information Consortium, Web of Science, SPORTDiscus and Cumulative Index to Nursing & Allied Health Literature) and supplementary searches to May 2022. Information regarding study design, accelerometer data collection methods and outcomes were extracted for each accelerometer measurement (study wave). Random effects meta-analyses and narrative syntheses were used to examine associations of methodological factors with participant recruitment, adherence and data loss. RESULTS: 123 accelerometer data collection waves were identified from 95 studies (92.5% from high-income countries). In-person distribution of accelerometers was associated with a greater proportion of invited participants consenting to wear an accelerometer (+ 30% [95% CI 18%, 42%] compared to postal distribution), and adhering to minimum wear criteria (+ 15% [4%, 25%]). The proportion of participants meeting minimum wear criteria was higher when accelerometers were worn at the wrist (+ 14% [ 5%, 23%]) compared to waist. Daily wear-time tended to be higher in studies using wrist-worn accelerometers compared to other wear locations. Reporting of information regarding data collection was inconsistent. CONCLUSION: Methodological decisions including accelerometer wear-location and method of distribution may influence important data collection outcomes including recruitment and accelerometer wear-time. Consistent and comprehensive reporting of accelerometer data collection methods and outcomes is needed to support development of future studies and international consortia. Review supported by the British Heart Foundation (SP/F/20/150002) and registered (Prospero CRD42020213465).