Pathways between multiple sclerosis, sleep disorders, and cognitive function: Longitudinal findings from The Nurses' Health Study.

BACKGROUND: The potential mediating and moderating effects of sleep disorders on cognitive outcomes in multiple sclerosis (MS) have been insufficiently studied. OBJECTIVES: To determine direct and indirect longitudinal associations between sleep disorders and perceived cognitive dysfunction in women with MS. METHODS: The 2013 and 2017 waves of the Nurses' Health Study (n = 63,866) were utilized. All diagnoses and symptoms including MS (n = 524) were self-reported. Subjective cognitive function was measured using a composite score of four memory items and three binary outcomes that assessed difficulty following instructions, conversations/plots, and street navigation. Moderating and mediating effects of diagnosed/suspected obstructive sleep apnea (OSA), sleepiness, and insomnia between MS and cognition were estimated using the four-way decomposition method. RESULTS: Prevalence of diagnosed/suspected OSA, sleepiness, and insomnia in 2013 were higher for nurses with MS (NwMS). NwMS were more likely to report cognitive difficulties in 2017. Insomnia mediated 5.4%-15.1% of the total effect between MS and following instructions, conversations/plots, and memory impairment, while sleepiness mediated 8.6%-12.3% of the total effect for these outcomes. In interaction analyses, OSA significantly accounted for 34% of the total effect between MS and following instructions. CONCLUSION: Prevalent OSA, insomnia, and sleepiness could differentially moderate or mediate the effect of MS on cognition in women with MS.

Sleep-disordered breathing and neurocognitive function in multiple sclerosis: Differential associations across cognitive domains.

BACKGROUND: Sleep disorders are common in people with multiple sclerosis (PwMS) and could contribute to cognitive dysfunction. However, effects of pathological sleep on cognitive domains are insufficiently characterized. OBJECTIVE: To evaluate associations between cognitive performance and polysomnographic (PSG)-based sleep disturbances in PwMS. METHODS: PwMS with known/suspected untreated obstructive sleep apnea (OSA, N = 131) underwent PSG and cognitive tests: Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), California Verbal Learning Test-II (CVLT-II), Brief Visuospatial Memory Test-Revised (BVMT-R Total and Delayed), Judgment of Line Orientation (JLO), Controlled Oral Word Association Test (COWAT), Trail Making Test, Go/No-Go, and Nine-Hole Peg Test (NHPT). RESULTS: Apnea severity measures were associated with worse processing speed, attention, and working memory (SDMT); immediate and delayed visual memory (BVMT-R Total and Delayed); attention, psychomotor speed, and cognitive flexibility (Trails); and manual dexterity and visuomotor coordination (NHPT) (ps ⩽ 0.011). Sleep macrostructure measures showed stronger associations with verbal memory and response inhibition (CVLT-II Total Recognition Discriminability Index), and immediate visual memory (BVMT-R Total) (ps ⩽ 0.011). CONCLUSIONS: Pathological sleep, including hypoxia, sleep fragmentation, and disturbances in sleep/wake states, are differentially associated with worse cognitive performance in PwMS. These findings could inform future personalized approaches to cognitive impairment in PwMS with sleep disorders. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02544373 (https://clinicaltrials.gov/ct2/show/NCT02544373).

Well-being at midlife: Correlates of mental health in ambulatory menopausal women with multiple sclerosis.

BACKGROUND: A majority of women with multiple sclerosis (MS) are diagnosed prior to menopause, yet their experiences during this transition are not well characterized. OBJECTIVES: To explore associations between mental health, sleep, and other quality of life metrics, and vasomotor symptoms (VMSs) in ambulatory, menopausal women with MS. METHODS: A secondary analysis was performed of baseline data from two trials enrolling ambulatory peri/postmenopausal women with MS: NCT02710214 (N = 24, bothersome VMS) and NCT04002934 (ongoing, N = 35, myelin repair). Measures analyzed were 36-Item Short-Form Survey (SF-36) (primary scale: general mental health), subjective sleep quality (Pittsburg Sleep Quality Index), VMS (daily diary, interference), mood (Center for Epidemiologist Studies-Depression Scale (CES-D)), walking impairment (timed 25-foot walk (T25FW)), and global disability (Expanded Disability Status Scale (EDSS)). RESULTS: Participants' characteristics (N = 59) were: mean age 51.8 years (SD = 3.4), mean disease duration 11.3 years (SD = 7.6), median EDSS 3.0 (IQR = 2.0-4.0). Mental health was associated with better sleep quality (rho = -0.41, p = 0.019) and better mood (rho = -0.75, p < 0.001), but not with EDSS or T25FW (rho < 0.20, p > 0.10). Worse sleep quality also correlated with more frequent VMS (rho = 0.41, p = 0.02) and VMS interference (rho = 0.59, p < 0.001). CONCLUSIONS: Findings suggest that optimizing sleep quality, mood, and hot flash quantity/interference could substantially improve mental health in menopausal women with MS-and highlight an important care gap in this population.

Validation of an obstructive sleep apnea symptom inventory in persons with multiple sclerosis.

BACKGROUND: Improved screening for obstructive sleep apnea (OSA) could enhance multiple sclerosis (MS) clinical care; yet the utility of current screening tools for OSA have yet to be evaluated in persons with multiple sclerosis (PwMS). OBJECTIVES: The STOP-Bang Questionnnaire is an 8-item screening tool for OSA that is commonly used in non-MS samples. The aim of this study was to assess the validity of the STOP-Bang in PwMS. METHODS: STOP-Bang and polysomnography data were analyzed from n = 200 PwMS. Sensitivity, specificity, positive-, and negative-predictive value (PPV and NPV) were calculated, with receiving operating characteristic (ROC) curves, for each STOP-Bang threshold score, against polysomnography-confirmed OSA diagnosis at three apnea severity thresholds (mild, moderate, and severe). RESULTS: Nearly 70% had a STOP-Bang score of ⩾3% and 78% had OSA. The STOP-Bang at a threshold score of 3 provided sensitivities of 87% and 91% to detect moderate and severe OSA, respectively; and NPV of 84% and 95% to identify PwMS without moderate or severe OSA, respectively. Sensitivity to detect milder forms of OSA was 76%. The NPV to identify persons without milder forms of OSA was 40%. CONCLUSION: The STOP-Bang Questionnaire is an effective tool to screen for moderate and severe OSA in PwMS, but may be insufficient to exclude mild OSA.

Multiple sclerosis relapse risk in the postoperative period: Effects of invasive surgery and anesthesia.

BACKGROUND: Postoperative multiple sclerosis (MS) relapses are a concern among patients and providers. OBJECTIVE: To determine whether MS relapse risk is higher postoperatively. METHODS: Data were extracted from medical records of MS patients undergoing surgery at a tertiary center (2000-2016). Conditional logistic regression estimated within-patient unadjusted and age-adjusted odds of postoperative versus preoperative relapse. RESULTS: Among 281 patients and 609 surgeries, 12 postoperative relapses were identified. The odds of postoperative versus preoperative relapse in unadjusted (odds ratio (OR) = 0.56, 95% confidence interval (CI) = 0.18-1.79; p = 0.33) or age-adjusted models (OR = 0.66, 95% CI = 0.20-2.16; p = 0.49) were not increased. CONCLUSIONS: Surgery/anesthesia exposure did not increase postoperative relapse risk. These findings require confirmation in larger studies.

Restless legs syndrome and health-related quality of life in adults with multiple sclerosis.

Restless legs syndrome (RLS) is a sleep disorder that may exacerbate many of the symptoms and consequences of multiple sclerosis (MS), and may have further implications for health-related quality of life (HRQOL). The present study examined the relationships among RLS, symptoms and HRQOL in people with MS. Participants with MS (n = 275) completed the Cambridge-Hopkins Restless Legs Syndrome Questionnaire, the International Restless Legs Syndrome Study Group Scale, the Multiple Sclerosis Impact Scale, the Pittsburgh Sleep Quality Index, the Fatigue Severity Scale, the Hospital Anxiety and Depression Scale and the Patient Determined Disease Steps. There were 74 (26.9%) persons with MS who had RLS (MS + RLS). The MS + RLS group reported worse physical and psychological HRQOL (p = 0.020 and p = 0.017, respectively) and greater perceived fatigue (p = 0.006) and anxiety symptoms (p = 0.042) than the MS-only group. Within the MS + RLS group, RLS severity was associated with physical (r = 0.43) and psychological (r = 0.46) HRQOL, sleep quality (r = 0.38), perceived fatigue (r = 0.28), depression (r = 0.38) and anxiety (r = 0.28). The relationships between RLS severity and the domains of HRQOL were attenuated when accounting for fatigue, depression and/or anxiety. Worse RLS severity was associated with reduced HRQOL, which was accounted for by fatigue, depression and anxiety.

Daily Temporal Associations Between Physical Activity and Symptoms in Multiple Sclerosis.

Background: Symptom severity is negatively associated with physical activity in multiple sclerosis (MS). However, it is unclear how physical activity and symptoms correlate on a day-to-day basis in persons with MS. Purpose: To determine the temporal within-person associations of pain, fatigue, depressed mood, and perceived cognitive function with physical activity in MS. Methods: Ambulatory adults with MS (N = 107) completed 7 days of home monitoring. Continuous physical activity data (assessed via wrist-worn accelerometer) and concurrent ecological momentary assessment (5X/day) of pain, fatigue, depressed mood, and perceived cognitive function were collected. Data were analyzed using multilevel mixed modeling. Results: Fatigue and depressed mood demonstrated bidirectional associations with physical activity, whereas pain and cognitive function did not. Higher than usual fatigue (B = -5.83, p = .001) and depressed mood (B = -4.12, p = .03) were followed by decreased physical activity. In contrast, higher than usual physical activity was associated with subsequent decline in fatigue (B = -0.001, p = .02) and depressed mood (B = -0.0007, p = .02); however, the association between physical activity and fatigue varied across the day. Conclusions: Physical activity is dynamically related to fatigue and mood on a moment-to-moment basis in MS. Efforts to increase physical activity in MS must incorporate a focus on how symptoms affect and are affected by activity.

Development of a person-centered conceptual model of perceived fatigability.

PURPOSE: Perceived fatigability, reflective of changes in fatigue intensity in the context of activity, has emerged as a potentially important clinical outcome and quality of life indicator. Unfortunately, the nature of perceived fatigability is not well characterized. The aim of this study is to define the characteristics of fatigability through the development of a conceptual model informed by input from key stakeholders who experience fatigability, including the general population, individuals with multiple sclerosis (MS), and individuals with fibromyalgia (FM). METHODS: Thirteen focus groups were conducted with 101 participants; five groups with n = 44 individuals representing the general population, four groups with n = 26 individuals with MS, and four groups with n = 31 individuals with FM. Focus group data were qualitatively analyzed to identify major themes in the participants' characterizations of perceived fatigability. RESULTS: Seven major themes were identified: general fatigability, physical fatigability, mental fatigability, emotional fatigability, moderators of fatigability, proactive and reactive behaviors, and temporal aspects of fatigability. Relative to those in the general sample, FM or MS groups more often described experiencing fatigue as a result of cognitive activity, use of proactive behaviors to manage fatigability, and sensory stimulation as exacerbating fatigability. CONCLUSIONS: Fatigability is the complex and dynamic process of the development of physical, mental, and/or emotional fatigue. Trait- and state-like biological, psychological, social, and environmental moderators contribute to tremendous variability in fatigability (both between and within-person variability). Future research to further characterize fatigability across populations, test treatments for fatigability, and develop new measures of this construct are greatly needed.

Pain, Fatigue, and Cognitive Symptoms Are Temporally Associated Within but Not Across Days in Multiple Sclerosis.

OBJECTIVE: To examine the temporal associations, within day and day to day, between pain, fatigue, depressed mood, and cognitive function in multiple sclerosis (MS). DESIGN: Repeated-measures study involving 7 days of ecological momentary assessment (EMA) of symptoms 5 times a day; multilevel mixed models were used to analyze data. SETTING: Community. PARTICIPANTS: Ambulatory adults (N=107) with MS. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: EMA of pain, fatigue, depressed mood, and cognitive function rated on a 0 to 10 scale. RESULTS: Fatigue and pain were linked within day such that higher pain was associated with higher subsequent fatigue (B=.09, P=.04); likewise, higher fatigue was associated with higher pain in the following time frame (B=.05, P=.04). Poorer perceived cognitive function preceded increased subsequent pain (B=.08, P=.007) and fatigue (B=.10, P=.01) within day. Depressed mood was not temporally linked with other symptoms. In terms of day-to-day effects, a day of higher fatigue related to decreased next day fatigue (B=-.16, P=.01), and a day of higher depressed mood related to increased depressed mood the next day (B=.17, P=.01). There were no cross-symptom associations from one day to the next. CONCLUSIONS: Findings provide new insights on how common symptoms in MS relate to each other and vary within and over days. Pain and fatigue show evidence of a dynamic bidirectional relation over the course of a day, and worsening of perceived cognitive function preceded worsening of both pain and fatigue. Most temporal associations between symptoms occur within the course of a day, with relatively little carryover from one day to the next.

Ecological Momentary Assessment of Pain, Fatigue, Depressive, and Cognitive Symptoms Reveals Significant Daily Variability in Multiple Sclerosis.

OBJECTIVE: To describe the daily variability and patterns of pain, fatigue, depressed mood, and cognitive function in persons with multiple sclerosis (MS). DESIGN: Repeated-measures observational study of 7 consecutive days of home monitoring, including ecological momentary assessment (EMA) of symptoms. Multilevel mixed models were used to analyze data. SETTING: General community. PARTICIPANTS: Ambulatory adults (N=107) with MS recruited through the University of Michigan and surrounding community. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: EMA measures of pain, fatigue, depressed mood, and cognitive function rated on a 0 to 10 scale, collected 5 times a day for 7 days. RESULTS: Cognitive function and depressed mood exhibited more stable within-person patterns than pain and fatigue, which varied considerably within person. All symptoms increased in intensity across the day (all P<.02), with fatigue showing the most substantial increase. Notably, this diurnal increase varied by sex and age; women showed a continuous increase from wake to bedtime, whereas fatigue plateaued after 7 pm for men (wake-bed B=1.04, P=.004). For the oldest subgroup, diurnal increases were concentrated to the middle of the day compared with younger subgroups, which showed an earlier onset of fatigue increase and sustained increases until bed time (wake-3 pm B=.04, P=.01; wake-7 pm B=.03, P=.02). Diurnal patterns of cognitive function varied by education; those with advanced college degrees showed a more stable pattern across the day, with significant differences compared with those with bachelor-level degrees in the evening (wake-7 pm B=-.47, P=.02; wake-bed B=-.45, P=.04). CONCLUSIONS: Findings suggest that chronic symptoms in MS are not static, even over a short time frame; rather, symptoms-fatigue and pain in particular-vary dynamically across and within days. Incorporation of EMA methods should be considered in the assessment of these chronic MS symptoms to enhance assessment and treatment strategies.

How Do Pain, Fatigue, Depressive, and Cognitive Symptoms Relate to Well-Being and Social and Physical Functioning in the Daily Lives of Individuals With Multiple Sclerosis?

OBJECTIVE: To examine the relative association between daily change in pain, fatigue, depressed mood, and cognitive function and 4 outcomes-positive affect and well-being, ability to participate in social roles and activities, upper extremity (UE) functioning, and lower extremity (LE) functioning. DESIGN: Data analysis, multilevel mixed modeling. SETTING: General community. PARTICIPANTS: Ambulatory adults (N=102) with multiple sclerosis. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Customized short-forms of the Quality of Life in Neurological Disorders positive affect and well-being, UE functioning, and LE functioning item banks and the Patient-Reported Outcomes Measurement Information System ability to participate in social roles and activities item bank adapted for daily use and administered as end-of-day diaries. RESULTS: Above and beyond the effects of demographic and clinical covariates, daily pain was associated with 3 of the 4 outcomes; days of higher than usual pain were related to lower same-day social participation (unstandardized ß, B=-1.00; P=.002), UE functioning (B=-1.04; P=.01), and LE functioning (B=-.71; P=.04). Daily fatigue and depressed mood were independently related to daily positive affect and well-being; days of worse fatigue (B=-.54; P=.006) and depressed mood (B=-1.17; P<.0001) were related to lower same-day well-being. CONCLUSIONS: The results indicate the role of fluctuations in symptoms in daily functioning and quality of life of individuals with multiple sclerosis. Daily increases in pain intensity are related to social and physical functioning, whereas increases in fatigue and depressed mood are related to lower daily well-being. Findings implicate a person-centered approach to monitoring and treating symptoms.

Sleep Disorders in Multiple Sclerosis.

Recent studies suggest that individuals with multiple sclerosis (MS) are at increased risk for sleep disturbances and that sleep disturbances contribute to fatigue and other chronic symptoms in MS. Although fatigue occurs commonly in people with MS, this symptom is often attributed to MS-specific pathology. Consequently, sleep disorders are often unrecognized and untreated in this population. Timely diagnosis and treatment of sleep problems in MS offer a new opportunity to ameliorate some of the daytime fatigue experienced by patients with MS. To increase this opportunity, the practitioner should be comfortable performing basic screening for common sleep complaints among patients with MS. The objectives of this review are to summarize the latest relevant data on sleep disorders in MS and offer a helpful approach to the identification and workup of the most common sleep problems in this population. Unexplored research avenues and opportunities to address important questions at the interface of sleep and MS are also discussed.

Investigating disparities in smoking cessation treatment for veterans with multiple sclerosis: A national analysis.

BACKGROUND AND AIMS: Smoking is a risk factor for multiple sclerosis (MS) development, symptom burden, decreased medication efficacy, and increased disease-related mortality. Veterans with MS (VwMS) smoke at critically high rates; however, treatment rates and possible disparities are unknown. To promote equitable treatment, we aim to investigate smoking cessation prescription practices for VwMS across social determinant factors. METHODS: We extracted data from the national Veterans Health Administration electronic health records between October 1, 2017, and September 30, 2018. To derive marginal estimates of the association of MS with receipt of smoking-cessation pharmacotherapy, we used propensity score matching through the extreme gradient boosting machine learning model. VwMS who smoke were matched with veterans without MS who smoke on factors including age, race, depression, and healthcare visits. To assess the marginal association of MS with different cessation treatments, we used logistic regression and conducted stratified analyses by sex, race, and ethnicity. RESULTS: The matched sample achieved a good balance across most covariates, compared to the pre-match sample. VwMS (n = 3320) had decreased odds of receiving prescriptions for nicotine patches ([Odds Ratio]OR = 0.86, p < .01), non-patch nicotine replacement therapy (NRT; OR = 0.81, p < .001), and standard practice dual NRT (OR = 0.77, p < .01), compared to matches without MS (n = 13,280). Men with MS had lower odds of receiving prescriptions for nicotine patches (OR = 0.88, p = .05), non-patch NRT (OR = 0.77, p < .001), and dual NRT (OR = 0.72, p < .001). Similarly, Black VwMS had lower odds of receiving prescriptions for patches (OR = 0.62, p < .001), non-patch NRT (OR = 0.75, p < .05), and dual NRT (OR = 0.52, p < .01). The odds of receiving prescriptions for bupropion or varenicline did not differ between VwMS and matches without MS. CONCLUSION: VwMS received significantly less smoking cessation treatment, compared to matched controls without MS, showing a critical gap in health services as VwMS are not receiving dual NRT as the standard of care. Prescription rates were especially lower for male and Black VwMS, suggesting that under-represented demographic groups outside of the white female category, most often considered as the "traditional MS" group, could be under-treated regarding smoking cessation support. This foundational work will help inform future work to promote equitable treatment and implementation of cessation interventions for people living with MS.

Resilience, mental health, sleep, and smoking mediate pathways between lifetime stressors and Multiple Sclerosis severity.

Intro: Lifetime stressors (e.g., poverty, violence, discrimination) have been linked to Multiple Sclerosis (MS) features; yet mechanistic pathways and relationships with cumulative disease severity remain nebulous. Further, protective factors like resilience, that may attenuate the effects of stressors on outcomes, are seldom evaluated. Aim: To deconstruct pathways between lifetime stressors and cumulative severity on MS outcomes, accounting for resilience. Methods: Adults with MS (N=924) participated in an online survey through the National MS Society listserv. Structural Equation Modeling was used to examine the direct and indirect effect of lifetime stressors (count/severity) on MS severity (self-reported disability, relapse burden, fatigue, pain intensity and interference), via resilience, mental health (anxiety and depression), sleep disturbance, and smoking. Results: The final analytic model had excellent fit (GFI=0.998). Lifetime stressors had a direct relationship with MS severity (ß=0.27, p<.001). Resilience, mental health, sleep disturbance, and smoking significantly mediated the relationship between lifetime stressors and MS severity. The total effect of mediation was significant (ß=0.45). Conclusions: This work provides foundational evidence to inform conceptualization of pathways by which stress could influence MS disease burden. Resilience may attenuate effects of stressors, while poor mental health, smoking, and sleep disturbances may exacerbate their impact. Parallel with usual care, these mediators could be targets for early multimodal therapies to improve disease course.

The Interplay Among Natural Menopause, Insomnia, and Cognitive Health: A Population-Based Study.

Purpose: The interrelationships among age at menopause, sleep, and brain health have been insufficiently studied. This study sought to examine the influence of age at natural menopause and insomnia symptoms on long-term cognitive function among US women. Patients and Methods: Our study included a nationally representative cohort of US adults age 50+ from the Health and Retirement Study (2008-2018). We restricted this cohort to 5880 women age 50+, from a diverse racial and ethnic groups. Age at menopause was retrieved from baseline (2008) for women having natural menopause. Five questions were used to identify women with insomnia symptoms (2010 and 2012): trouble falling asleep, nighttime awakenings, early morning awakenings, feelings of nonrestorative sleep, and use of sleep aids. A battery of four neuropsychological tests was conducted biennially (years) to evaluate cognitive function. Longitudinal associations between age at natural menopause and cognitive function were estimated with mixed effects models with a random intercept. Insomnia symptoms were examined as potential mediators or modifiers in the pathway between age at menopause and cognition. Results: One year earlier in age at menopause was associated with a 0.49 lower mean in composite cognitive score, in any given survey year (adjusted p = 0.002). Earlier age at menopause was associated with higher risk of developing insomnia symptoms (eg, trouble falling asleep OR = 0.97; 95% CI: 0.96, 0.99), and insomnia symptoms were associated with worse cognitive performance (eg, trouble falling asleep, beta = -0.5, p-value = 0.02). Therefore, insomnia symptoms could potentially mediate the association between age at natural menopause and cognition. Conclusion: Earlier age at menopause is associated with a lower score in cognitive performance. This association may be mediated by insomnia symptoms. Our findings spotlight that among women who experience early menopause, there is the need for studies of sleep-based interventions to mitigate cognitive decline.

Respiratory infection risk in positive airway pressure therapy users: a retrospective cohort study.

STUDY OBJECTIVES: Concerns regarding the risk of positive airway pressure (PAP)-associated respiratory infection (RI) have shaped consumer views toward PAP device use and maintenance. However, data regarding temporal associations between PAP use and risk for RIs are limited. The purpose of the present study was to examine longitudinal associations between PAP use and risk of clinically significant RIs in a cohort of patients with obstructive sleep apnea. METHODS: The frequency of clinically reported respiratory RIs pre- and post-PAP use were compared in a sample of 482 adult patients with obstructive sleep apnea who underwent PAP titration at a large academic sleep center between 2011 and 2014. RIs were identified by clinical record review beginning two years before and ending two years after the participants' PAP titration. Presence of longitudinal standard PAP data download reports identified PAP users from nonusers. PAP adherence was defined as at least 4 hours of use per day, five days per week for at least 70% of days. Poisson regression models, adjusted for age, sex, body mass index, and the number of pre-PAP use RIs were utilized to examine associations between PAP use and subsequent RIs. RESULTS: Poisson regression models adjusted for age, sex, body mass index, and the number of pre-PAP use RIs did not show associations between PAP therapy use and rate of post-PAP use RIs (rate ratio = 1.27, 95% confidence interval: 0.86-1.86). A sensitivity analysis that included only PAP users with difference in PAP adherence showed similar results (rate ratio = 0.65, 95% confidence interval: 0.32-1.30). CONCLUSIONS: Among adults with obstructive sleep apnea, we did not find evidence for association between PAP use/adherence and increased RI frequency. These data offer new information that could assuage patients with obstructive sleep apnea who are considering PAP deferral based on RI concerns. CITATION: Gavidia R, Shieu MM, Dunietz GL, Braley TJ. Respiratory infection risk in positive airway pressure therapy users: a retrospective cohort study. J Clin Sleep Med. 2023;19(10):1769-1773.

The Impact of Sustained Ownership of a Pet on Cognitive Health: A Population-Based Study.

Objectives: To examine associations between sustained ownership of a pet and cognitive outcomes among a national sample of U.S. adults. Methods: Weighted linear mixed models were estimated using the Health and Retirement Study (2010-2016, n = 1369) to compare repeated measures of cognitive function between respondents who endorsed owning a pet in a sustained manner (>5 years), versus those who owned a pet ≤5 years, and non-pet owners. Results: Respondents aged 65+ who owned a pet >5 years demonstrated higher composite cognitive scores, compared to non-pet owners (ß = .76, p = .03). Sustained pet ownership was associated with higher immediate (ß = .3, p = .02) and delayed (ß = .4, p = .007) word recall scores. There were no significant differences in cognitive scores between pet owners and non-owners aged < 65. Discussion: Sustained ownership of a pet could mitigate cognitive disparities in older adults. Further studies are needed to examine potential causal pathways, including physical activity and stress buffering, versus selection effects.

Associations among stressors across the lifespan, disability, and relapses in adults with multiple sclerosis.

INTRODUCTION: Stress and adversity during childhood, adolescence, and adulthood could impact the present and future health and well-being of people with multiple sclerosis (PwMS); however, a lifespan approach and nuanced stressor data are scarce in this nascent area of research. Our aim was to examine relationships among comprehensively measured lifetime stressors and two self-reported MS outcomes: (1) disability and (2) relapse burden changes since COVID-19 onset. METHODS: Cross-sectional data were collected from a nationally distributed survey of U.S.-based adults with MS. Hierarchical block regressions were used to sequentially evaluate contributions to both outcomes independently. Likelihood ratio (LR) tests and Akaike information criterion (AIC) were used to evaluate additional predictive variance and model fit. RESULTS: A total of 713 participants informed either outcome. Most respondents (84%) were female, 79% had relapsing remitting multiple sclerosis (MS), and mean (SD) age was 49 (12.7) years. Childhood (R2  = .261, p < .001; AIC = 1063, LR p < .05) and adulthood stressors (R2  = .2725, p < .001, AIC = 1051, LR p < .001) contributed significantly to disability, above and beyond prior nested models. Only adulthood stressors (R2  = .0534, p < .001; AIC = 1572, LR p < .01) significantly contributed above the nested model for relapse burden changes since COVID-19. CONCLUSIONS: Stressors across the lifespan are commonly reported in PwMS and could contribute to disease burden. Incorporating this perspective into the "lived experience with MS" could facilitate personalized health care by addressing key stress-related exposures and inform intervention research to improve well-being.

Fatigue, pain interference, and psychiatric morbidity in multiple sclerosis: The role of childhood stress.

BACKGROUND: Multiple sclerosis (MS) is a progressive, autoimmune disease of the central nervous system that affects nearly one million Americans. Despite the existence of immunomodulatory therapies to slow physical and cognitive disability progression, interventions to ameliorate common symptoms of MS, including fatigue and pain, remain limited. Poor understanding of risk factors for these symptoms may contribute to treatment challenges. In recent years, childhood stress has been investigated as a risk factor for chronic autoimmune conditions including MS; yet remarkably few studies have investigated the relationship between childhood stressors and chronic MS symptoms. Our aim was to examine clusters of stressors and three key features of MS: fatigue, pain interference, and psychiatric morbidity. METHODS: Cross-sectional data were collected from a sample of People with MS (PwMS) via a national web-based survey that assessed the presence and type of childhood stressors and MS clinical features. Hierarchical block regression was used to assess associations among emotional, physical, and environmental childhood stressors and three clinical features commonly experienced by PwMS. RESULTS: N = 719 adults with MS (aged 21-85) completed the survey. Childhood emotional and physical stressors were significantly associated with overall presence of fatigue (p = 0.02; p<0.03) and pain interference (p<0.001; p<0.001) in adulthood, as well as the magnitude of both outcomes. Environmental stressors (p<0.001), in addition to emotional (p<0.001) and physical (p<0.001) stressors were significantly associated with psychiatric morbidity in PwMS. CONCLUSION: Childhood stress may predict fatigue, psychiatric morbidity, and pain in adults with MS. Further research is needed to show cause and effect; however, if an association exists, strategies to mitigate the impact of childhood stress could offer new pathways to reduce the severity of these symptoms. Broadly, this work adds to the body of evidence supporting upstream preventive measures to help address the stress on children and families.

Differences in diffusion tensor imaging-derived metrics in the corpus callosum of patients with multiple sclerosis without and with gadolinium-enhancing cerebral lesions.

OBJECTIVE: To analyze differences in corpus callosum diffusion tensor imaging metrics among patients with relapsing-remitting multiple sclerosis (MS) (RRMS) and secondary progressive MS (SPMS) with enhancing and nonenhancing cerebral lesions. METHODS: One-way analysis of variance and multiple linear regression models were used to assess the relationship between MS subtype, the presence of enhancing lesions, and fractional anisotropy (FA)/mean diffusivity (MD) values of the genu, body, and splenium of the corpus callosum from 22 patients with RRMS and 25 patients with SPMS. RESULTS: Analyses of variance: The subjects with SPMS with enhancing lesions had significantly lower genu and body FA values than those with nonenhancing SPMS and significantly lower genu, body, and splenium FA values than those with RRMS. Regression models: Enhancement was associated with decreased genu FA (P = 0.014). Secondary progressive MS was associated with decreased genu (P = 0.002) and splenium FA (P < 0.001) and significantly increased MD values. CONCLUSION: Patients with SPMS with enhancing lesions may be at increased risk for neuronal damage compared to nonenhancing SPMS and RRMS subtypes.