Data-driven analysis shows robust links between fatigue and depression in early multiple sclerosis

Fatigue is common and disabling in multiple sclerosis, yet its mechanisms are poorly understood. In particular, overlap in measures of fatigue and depression complicates interpretation. A clearer understanding of relationships between fatigue and key clinical, neuropsychiatric and imaging variables including depression could yield clinically relevant mechanistic insight. We applied a data-driven multivariate network approach to quantify relationships between fatigue and other variables in early multiple sclerosis. Data were collected from Scottish patients with newly diagnosed, immunotherapy-naive, relapsing-remitting multiple sclerosis at baseline and month 12 follow-up in FutureMS, a nationally representative multicentre cohort. Subjective fatigue was assessed using the validated Fatigue Severity Scale. Detailed phenotyping included measures assessing physical disability, affective disorders, objective cognitive performance, subjective sleep quality, and structural brain imaging. Bivariate correlations between fatigue and other variables were calculated. Network analysis was then conducted to estimate partial correlations between variables, after accounting for all other included variables. Secondary networks included individual depressive symptoms, to control for overlapping symptom items in measures of fatigue and depression. Data from 322 participants at baseline, and 323 at month 12, were included. At baseline, 49.5% of the cohort reported clinically significant fatigue. Bivariate correlations confirmed that fatigue severity was significantly correlated with all included measures of physical disability, affective disturbance (anxiety and depression), cognitive performance (processing speed and memory/attention), and sleep quality, but not with structural brain imaging variables including normalized lesion and grey matter volumes. In the network analysis, fatigue showed strong correlations with depression, followed by Expanded Disability Status Scale. Weak connections with walking speed, subjective sleep quality and anxiety were identified. After separately controlling for measurement of tiredness in our measure of depression, some key depressive symptoms (anhedonia, subjective concentration deficits, subjectively altered speed of movement, and appetite) remained linked to fatigue. Conversely, fatigue was not linked to objective cognitive performance, white matter lesion volume, or grey matter volumes (cortical, subcortical or thalamic). Results were consistent at baseline and month 12. Depression was identified as the most central variable in the networks. Correlation stability coefficients and bootstrapped confidence intervals of the edge weights supported stability of the estimated networks. Our findings support robust links between subjective fatigue and depression in early relapsing-remitting multiple sclerosis, despite absence of links between fatigue and either objective cognitive performance, or structural brain imaging variables. Depression, including specific depressive symptoms, could be a key target of treatment and research in multiple sclerosis-related fatigue.

Poor Diet, Long Sleep, and Lack of Physical Activity Are Associated with Inflammation among Non-Demented Community-Dwelling Elderly

Inflammation in elderly is associated with physical and cognitive morbidity and mortality. We aimed to explore the association of modifiable lifestyle parameters with inflammation among non-demented, community-dwelling elderly. A sub-sample of 117 patients with mild cognitive impairment (MCI, n = 63) and cognitively non-impaired controls (CNI, n = 54) were recruited from a large, population-based cohort in Crete, Greece, of 3140 elders (> 60 years old). All participants underwent assessment of medical history/physical examination, extensive neuropsychiatric/neuropsychological evaluation, diet, three-day 24-h actigraphy, subjective sleep, physical activity, and measurement of IL-6 and TNFα plasma levels. Associations between inflammatory markers and diet, objective sleep duration, subjective sleep quality, and lack of physical activity were assessed using multivariate models. Regression analyses in the total group revealed significant associations between TNF-α and low vegetable consumption (p = 0.003), and marginally with objective long nighttime sleep duration (p = 0.04). In addition, IL-6 was associated with low vegetable consumption (p = 0.001) and lack of physical activity (p = 0.001). Poor diet and lack of physical activity appear to be modifiable risk factors of inflammation, whereas long sleep appears to be a marker of increased inflammatory response in elderly. Our findings may have clinical implications given the association of inflammatory response with morbidity, including cognitive decline, and mortality in elderly.

The effect of orthodontic treatment with fixed appliances on sleep quality in adults and adolescents in Saudi Arabia using Pittsburgh sleep quality index

Objectives: The aim of this study was to investigate the effect of pain caused by orthodontic fixed appliances on sleep quality of participants using the Pittsburgh Sleep Quality Index (PSQI). Materials and Methods: A previously validated Arabic version of PSQI was electronically distributed through different social media platforms and in waiting areas of orthodontic offices. Eligibility criteria included healthy adults and adolescents with orthodontic fixed appliances and with no systemic conditions that may affect sleep. The cut-off point used to determine poor sleep quality was (>5). Results: Three hundred and eighteen participants were included in the final analysis (28.9% males and 71.1% females). Both males and females with orthodontic fixed appliances had poor sleep quality with (Mean = 6.48, SD = 2.85, P = 0.000) for males, and (Mean = 7.18, SD = 2.87, P = 0.000) for females. Comparing males and females, we found that females scored higher than males in both subjective sleep quality and PSQI global score. Conclusion: Individuals undergoing orthodontic treatment with fixed appliances have poor sleep quality. Females undergoing orthodontic treatment tend to have poorer sleep quality compared to males.

The Association Between Dry Eye Disease With Depression, Anxiety and Sleep Disturbance During COVID-19

Objective: This study aimed to investigate the relationship between dry eye disease (DED) with anxiety and depression. Additionally, the mediating effect of sleep quality on this relationship was explored.Methods: 321 patients with DED were recruited from Tianjin Medical University Eye Hospital clinic and surveyed using demographic questionnaires, the Ocular Surface Disease Index (OSDI), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index (PSQI). Regression analysis and the bootstrap method were used to investigate the influence of sleep on the relationship between DED, anxiety and depression.Results: Among the patients with DED, 86 (26.79%), 85 (26.48%), and 54 (16.82%) patients presented with anxiety, depression, and both anxiety and depression respectively. The OSDI and PSQI score were positively correlated with depression and anxiety (all p < 0.01). The direct effects of OSDI on depression and anxiety were significant (P < 0.01). Additionally, the bootstrap test showed significant mediating effects of subjective sleep quality [95% CI [0.003–0.016] (depression); [0.001–0.011] (anxiety)] and sleep latency [95% CI [0.001–0.010] (depression); [0.001–0.008] (anxiety)]. These results indicated that the severity of DED symptoms, as measured by the OSDI score, affected anxiety and depression through a direct and an indirect pathway mediated by subjective sleep quality and sleep latency.Conclusions: The results indicated that there was a significant correlation between DED and anxiety and depression. Moreover, subjective sleep quality and sleep latency were a mediator of the relationship between DED symptoms and anxiety and depression.

Sleep disturbances in early clinical stages of psychotic and bipolar disorders: A meta-analysis

Objective: To provide a qualitative view and quantitative measure of sleep disturbances across and between early stages – clinical ultra high-risk and first episode – of psychotic and bipolar disorders. Methods: Electronic databases (PubMed, Cochrane, Embase, PsychINFO) were searched up to March 2021 for studies comparing sleep measures between individuals with an early stage and controls. Standard mean deviations (Cohen’s d effect sizes) were calculated for all comparisons and pooled with random-effects models. Chi-square tests were used for direct between-subgroups (ultra high-risk vs first episode) comparisons of standard mean deviations. The effects of age, sex ratio, symptoms and treatment were examined in meta-regression analyses. Results: A database search identified 13 studies that contrasted sleep measures between individuals with an early stage ( N = 537) and controls ( N = 360). We observed poorer subjective sleep quality (standard mean deviation = 1.32; 95% confidence interval, [1.01, 1.62]), shorter total sleep time (standard mean deviation =−0.44; 95% confidence interval, [−0.67, −0.21]), lower sleep efficiency (standard mean deviation = −0.72; 95% confidence interval, [−1.08, −0.36]), longer sleep onset latency (standard mean deviation = 0.75; 95% confidence interval, [0.45, 1.06]) and longer duration of wake after sleep onset (standard mean deviation = 0.49; 95% confidence interval, [0.21, 0.77]) were observed in early stages compared to controls. No significant differences were observed for any of the reported electroencephalographic parameters of sleep architecture. No significant between-subgroups differences were observed. Meta-regressions revealed a significant effect of the age and the antipsychotic status on subjective measures of sleep. Conclusion: The early stage population presents with significant impairments of subjective sleep quality continuity, duration and initiation. Systematic assessments of sleep in early intervention settings may allow early identification and treatment of sleep disturbances in this population.

Depressive Symptoms, Subjective Cognitive Decline, and Subjective Sleep Quality Are Associated with Slips and Falls: Data from the Community Health Survey in Korean Adults

<b><i>Background:</i></b> Identifying the risk factors for falls among the elderly population is arguably one of the most imperative public health issues in the current aging society. <b><i>Objectives:</i></b> This study aimed to determine the associations between depressive symptoms, subjective cognitive decline (SCD), and poor subjective sleep quality and the risk of slips/falls in a Korean older population. <b><i>Methods:</i></b> This cross-sectional study involved 228,340 elderly individuals living in Korea. Measurements included self-reported depressive symptoms, SCD, and self-reported sleep quality. The risk of slips/falls was dichotomized depending on whether slips/falls had occurred during the past year, and the associations between different risk factors and slips/falls were explored. Multiple logistic regression was used to obtain the odds ratios (ORs) and 95% confidence intervals (CIs). Complex sampling methods were used to estimate the weighted value of each participant. <b><i>Results:</i></b> The risk of slips/falls was significantly associated with high levels of depressive symptoms (adjusted OR 1.06, 95% CI: 1.05–1.07) and SCD (adjusted OR 1.33, 95% CI: 1.19–1.50). Regarding each sleep quality component, the adjusted ORs for slips/falls were 1.85 for very poor sleep quality, 1.49 for long sleep latency, 1.04 for &#x3c;5 h of sleep duration, 1.32 for low sleep efficiency, 2.78 for high sleep disturbance, 1.52 for the use of sleep medication ≥3 times a week, and 1.82 for high daytime dysfunction due to sleep problems compared to the respective good sleep conditions. <b><i>Conclusions:</i></b> Our results demonstrated that depressive symptoms, SCD, and poor subjective sleep quality are independent factors affecting the occurrence of slips/falls. Thus, efforts to manage depressive symptoms and cognitive decline early and to improve sleep quality can be an alternative strategy to decrease the likelihood of falls.

The Effect of Uncoupled Sleep and Dysfunctional Sleep Beliefs on Sleep Outcomes in Older Adults following Online Cognitive Behavioral Therapy for Insomnia: A Single-Group Non-randomized Trial (Preprint)

BACKGROUND The current Covid-19 pandemic has brought about a marked interest in sleep health, as well as an increased demand for telehealth services, such as online Cognitive Behavioral Therapy for insomnia (CBT-I). Older adults in particular report a high rate of sleep problems. Recent studies have suggested that dysfunctional sleep beliefs could contribute to the high rates of self-reported insomnia in this age group. In addition, older adults have an increased rate of uncoupled sleep, e.g. displaying an insomnia complaint in the absence of objectively measured poor sleep. It is essential to determine the prevalence of coupled and uncoupled sleep in older adults and to examine the efficacy of online CBT-I to improve sleep outcomes. OBJECTIVE This study aims to assess objective and subjective sleep quality and dysfunctional sleep beliefs in a sample of community-dwelling older adults aged 60-80 years with and without uncoupled sleep in Western Australia following digitally delivered CBT-I. METHODS Objective sleep was measured using wrist actigraphy, and subjective sleep quality via sleep diaries and the Pittsburgh Sleep Quality Index (PSQI). Dysfunctional sleep beliefs were assessed by the Dysfunctional Beliefs and Attitudes about Sleep scale (DBAS-16) prior to and following a four-week online CBT-I programme. Linear mixed model and generalised linear mixed model analyses were conducted to examine objective and subjective sleep onset latency, total sleep time, wake after sleep onset and number of awakenings as well as PSQI and DBAS16 scores, respectively. RESULTS 62 participants (55 females; 88.7%) completed the study. CBT-I effectively reduced dysfunctional sleep beliefs and PSQI scores across all sleep classifications, even in good sleepers without a sleep complaint. Objective and self-reported changes in sleep parameters were mainly demonstrated in complaining poor sleepers. Complaining good sleepers reported a decrease in the number of subjective sleep awakenings only. CONCLUSIONS Online CBT-I was effective in improving the sleep outcomes of individuals who had both subjective and objective poor sleep. However, as the online CBT-I reduced dysfunctional sleep beliefs in all sleep groups, further examination of dysfunctional sleep beliefs and whether they mediate the outcomes of digital CBT-I in older adults will need to be conducted. CLINICALTRIAL Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN 12619001509156; http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378451 INTERNATIONAL REGISTERED REPORT RR2-32705

Too Jittery to Sleep? Temporal Associations of Actigraphic Sleep and Caffeine in Adolescents

Caffeine consumption has been linked to poor sleep health in adolescents, but it is unknown whether poor sleep predicts caffeine consumption, and/or whether caffeine consumption predicts poor sleep, particularly when sleep is measured objectively. Data were collected from a micro-longitudinal sub-study of the age 15 wave of the Fragile Families and Child Wellbeing Study (n = 589). Adolescents wore an actigraphy device and completed daily surveys for ~1 week. Daily surveys assessed subjective sleep quality and caffeinated beverage consumption (0 = no caffeine, 1 = any caffeine). Separate mixed models assessed whether actigraphy-measured sleep duration, timing, maintenance efficiency, and subjective quality predicted next-day caffeinated beverage consumption within and between adolescents. Variability (standard deviation) of sleep duration and timing, sleep regularity index, and social jetlag were tested as additional between-person predictors. Lagged models tested whether daily caffeinated beverage consumption predicted sleep that night (n = 458). Adolescents with more variable sleep duration and midpoint had higher average odds of consuming caffeinated beverages compared to others. After adolescents consumed ≥1 caffeinated beverage, they had later sleep onset that night and wake time the next morning than usual versus when they did not consume caffeine. Curbing caffeinated beverage consumption may aid in the maintenance of regular sleep schedules and advance sleep timing in adolescents.

Association of Subjective Quality and Quantity of Sleep with Quality of Life among a General Population

This study aimed to determine whether both subjective sleep quality and sleep duration are directly associated with quality of life (QOL), as well as indirectly associated with QOL through insomnia symptoms. Individuals aged 20–69 years without mental illness (n = 9305) were enrolled in this web-based cross-sectional survey. The Short Form-8 was used to assess physical and mental QOL. We used the Pittsburgh Sleep Quality Index (PSQI) and extracted items related to subjective sleep quality and sleep duration. Insomnia symptoms were also extracted from the PSQI. The hypothesized models were tested using structural equation modeling. Worse sleep quality, but not shorter sleep duration, was related to worse physical QOL. Both worse sleep quality and shorter sleep duration were related to worse mental QOL. Insomnia symptoms mediated these relationships. Subgroup analyses revealed a U-shaped relationship between sleep duration and physical/mental QOL. However, the relationship between sleep quality and physical/mental QOL was consistent regardless of sleep duration. The results suggest that subjective sleep quality has a more coherent association with QOL than subjective sleep duration. Because of its high feasibility, a questionnaire on overall sleep quality could be a useful indicator in future epidemiological studies of strategies for improving QOL.