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Chronic pain conditions pose a significant global burden of disability, with epidemiological data indicating a rising incidence. Exercise training is commonly recommended as a standalone or complementary approach for managing various chronic pain conditions like low back pain, osteoarthritis, rheumatoid arthritis, fibromyalgia syndrome, and neuropathic pain. Regardless of the specific condition or underlying cause (e.g., autoimmune disease, chronic inflammation), exercise training consistently leads to moderate to large reductions in pain. Moreover, exercise yields numerous benefits beyond pain alleviation, including small-to-moderate improvements in disability, quality of life, and physical function. Despite its efficacy, there is a lack of comprehensive research delineating the optimal intensity, duration, and type of exercise for maximal benefits; however, evidence suggests that sustained engagement in regular exercise or physical activity is necessary to achieve and maintain reductions in both clinical pain intensity ratings and the level that pain interferes with activities of daily living. Additionally, the precise mechanisms through which exercise mitigates pain remain poorly understood and likely vary based on the pathophysiological mechanisms underlying each condition.
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For neurotypical adults, a single bout of low-to-moderate intensity physical activity usually transiently improves feelings of energy. Similar bouts of exercise have the opposite effect of increased feelings of fatigue when performed by samples with chronic multisymptom illnesses (CMIs) such as Long-COVID, Gulf War Illness (GWI), or Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The short-term adoption of regular moderate intensity physical activity (typical experiments are 1 to 6 months) among neurotypical adults results in small-to-moderate improvements in self-reported feelings of fatigue, energy, and vitality. Small improvements in these feelings, or no change at all, occur for CMIs, but limited data precludes strong conclusions. The mechanisms of exercise effects on fatigue, whether acute or chronic, are poorly understood but likely involve multiple neural circuits and associated transmitters. For CMIs, the mechanisms of acute worsening of fatigue with exercise may be driven by the yet unknown pathophysiological mechanisms of the disease (perhaps involving brain, immune and autonomic system dysfunction, and their interactions). Likewise, fatigue improvements may depend on whether chronic physical activity is a disease-modifying treatment.
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Chronic multisymptom illnesses (CMI) such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Long-COVID, and Gulf War Illness (GWI) are associated with an elevated risk of post-exertional malaise (PEM), an acute exacerbation of symptoms and other related outcomes following exercise. These individuals may benefit from personalized exercise prescriptions which prioritize risk minimization, necessitating a better understanding of dose-response effects of exercise intensity on PEM. METHODS: Veterans with GWI (n = 40) completed a randomized controlled crossover experiment comparing 20 min of seated rest to light-, moderate-, and vigorous-intensity cycling conditions over four separate study visits. Symptoms, pain sensitivity, cognitive performance, inflammatory markers (C-reactive protein and plasma cytokines) were measured before and within 1 h after exercise and seated rest. Physical activity behavior was measured ≥ 7 days following each study visit via actigraphy. Linear mixed effects regression models tested the central hypothesis that higher intensity exercise would elicit greater exacerbation of negative outcomes, as indicated by a significant condition-by-time interaction for symptom, pain sensitivity, cognitive performance, and inflammatory marker models and a significant main effect of condition for physical activity models. RESULTS: Significant condition-by-time interactions were not observed for primary or secondary measures of symptoms, pain sensitivity, cognitive performance, and a majority of inflammatory markers. Similarly, a significant effect of condition was not observed for primary or secondary measures of physical activity. CONCLUSIONS: Undesirable effects such as symptom exacerbation were observed for some participants, but the group-level risk of PEM following light-, moderate-, or vigorous-intensity exercise was no greater than seated rest. These findings challenge several prior views about PEM and lend support to a broader body of literature showing that the benefits of exercise outweigh the risks.
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Estudios Cruzados , Ejercicio Físico , Síndrome del Golfo Pérsico , Veteranos , Humanos , Masculino , Persona de Mediana Edad , Ejercicio Físico/fisiología , Femenino , Adulto , Proteína C-Reactiva/metabolismo , Cognición/fisiología , Citocinas/sangreRESUMEN
ABSTRACT: Over 20 million Americans are living with a substance use disorder (SUD) and nearly 100,000 die annually from drug overdoses, with a majority involving an opioid. Many people with SUD have co-occurring chronic pain and/or a mental health disorder. Exercise is a frontline treatment for chronic pain and is an effective strategy for reducing depression and anxiety and improving overall mental health. Several studies have shown that exercise improves SUD-related outcomes including abstinence; however, there is limited large-scale randomized clinical trial evidence to inform integration of exercise into practice. In this Call to Action, we aim to raise awareness of the specific issues that should be addressed to advance exercise as medicine in people with SUD including the challenges of co-occurring chronic pain, mental illness, and cardiopulmonary health conditions. In addition, specialized training for exercise professionals and other support staff should be provided on these issues, as well as on the multiple dimensions of stigma that can impair engagement in treatment and overall recovery in people with SUD.
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Dolor Crónico , Trastornos Relacionados con Sustancias , Humanos , Estados Unidos , Dolor Crónico/terapia , Trastornos Relacionados con Sustancias/terapia , Trastornos Relacionados con Sustancias/psicología , Salud MentalRESUMEN
Research on myofascial temporomandibular disorder (mTMD) has often focused on potential dysfunction in endogenous pain modulation. However, studies on the specific inhibitory and facilitatory components of endogenous pain modulation using conditioned pain modulation (CPM) and temporal summation of second pain (TSSP) have shown mixed results. This study aimed to 1) examine whether women with mTMD demonstrated efficient CPM compared to controls; 2) explore the association between independent measures of CPM and TSSP in women with mTMD relative to controls; and 3) determine whether resulting modulatory profiles differentially predicted pain intensity among cases. All participants were recruited from dental clinics. Cases were women who met the research diagnostic criteria for mTMD. Controls did not have facial pain on exam and were selected to be sociodemographically similar to cases. CPM and TSSP were assessed via independent psychophysical protocols. CPM was examined in linear mixed models predicting pain thresholds adjusted for age and stratified by TSSP. Mean CPM was estimated at a 2.2 (SD = 2.8) degree increase in pain thresholds (P ≤ .001), similar in cases and controls (P = .67). CPM was less efficient in cases with enhanced TSSP (P = .031), but not in controls. Although the double-pronociceptive profile of both low CPM and high TSSP trended higher among cases than controls, it did not predict higher levels of pain intensity among cases. This study does not support deficient inhibitory endogenous pain modulation in mTMD, but results suggest that inhibitory and facilitatory pain modulation should be examined concomitantly in the study of endogenous pain modulation. PERSPECTIVE: This manuscript presents a novel examination of inhibitory modulation by the level of facilitatory modulation in mTMD. The findings and approach may prove useful for mechanistic researchers studying endogenous pain modulation and clinical researchers seeking to jointly examine conditioned pain modulation and temporal summation in future research on chronic pain.
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The etiology and mechanism of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are poorly understood and no biomarkers have been established. Specifically, the relationship between the immunologic, metabolic, and gastrointestinal abnormalities associated with ME/CFS and their relevance to established symptoms of the condition remain unclear. Relying on data from two independent pairs of ME/CFS and control cohorts, one at rest and one undergoing an exercise challenge, we identify a state of suppressed acute-phase innate immune response to microbial translocation in conjunction with a compromised gut epithelium in ME/CFS. This immunosuppression, along with observed enhancement of compensatory antibody responses to counter the microbial translocation, was associated with and may be mediated by alterations in glucose and citrate metabolism and an IL-10 immunoregulatory response. Our findings provide novel insights into mechanistic pathways, biomarkers, and potential therapeutic targets in ME/CFS, including in the context of exertion, with relevance to both intestinal and extra-intestinal symptoms.
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Anxiety is common in people with major depressive disorder (MDD), yet the anxiolytic effects of acute exercise in MDD are unknown. The purpose of this analysis was to determine a potentially optimal acute exercise intensity for reducing state anxiety in women with MDD, the duration of the response, and the potential influences of depression severity and preferred-intensity exercise. Using a within-subject, randomized, counter-balanced design, 24 participants completed five separate visits including 20 min of steady-state bicycling at prescribed (via RPE) light, moderate, or hard intensities, a preferred/self-selected session, or a quiet rest (QR) session. State anxiety was measured via the State-Trait Anxiety Inventory (STAI-Y1) and anxiety visual analog scale (VAS) at pre-, immediately (VAS only), 10 min, and 30 min post-exercise. Depression was measured via the Beck Depression Inventory (BDI-II) pre-exercise. Moderate exercise resulted in a moderate state anxiety reduction compared to QR 10 min (STAI-Y1: g = 0.59, padj = 0.040) and 30 min post-exercise (STAI-Y1: g = 0.61, padj = 0.032). Pairwise differences indicated each exercise session decreased state anxiety pre to 10 min and 30 min post-exercise (all padj < 0.05) for the STAI-Y1, and for moderate and hard exercise from pre to each time point post-exercise (all padj < 0.05) for the VAS. Depression severity was associated with state anxiety (p < 0.01) but did not influence the overall results. Prescribed moderate intensity exercise led to greater reductions in state anxiety compared to preferred at 30 m (STAI-Y1: g = 0.43, p = 0.04). These findings suggest steady-state prescribed moderate exercise reduces state anxiety in women with MDD for at least 30 min following exercise regardless of their depression severity.
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TOPIC IMPORTANCE: Postacute sequelae of SARS-CoV-2 (PASC) is a long-term consequence of acute infection from COVID-19. Clinical overlap between PASC and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has been observed, with shared symptoms including intractable fatigue, postexertional malaise, and orthostatic intolerance. The mechanistic underpinnings of such symptoms are poorly understood. REVIEW FINDINGS: Early studies suggest deconditioning as the primary explanation for exertional intolerance in PASC. Cardiopulmonary exercise testing reveals perturbations related to systemic blood flow and ventilatory control associated with acute exercise intolerance in PASC, which are not typical of simple detraining. Hemodynamic and gas exchange derangements in PASC have substantial overlap with those observed with ME/CFS, suggestive of shared mechanisms. SUMMARY: This review illustrates exercise pathophysiologic commonalities between PASC and ME/CFS that will help guide future diagnostics and treatment.
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COVID-19 , Síndrome de Fatiga Crónica , Humanos , Síndrome de Fatiga Crónica/etiología , SARS-CoV-2 , Ejercicio Físico/fisiología , Prueba de EsfuerzoRESUMEN
Background: Post-exertional malaise (PEM) is considered a characteristic feature of chronic multi-symptom illnesses (CMI) like Gulf War illness (GWI); however, its pathophysiology remains understudied. Previous investigations in other CMI populations (i.e., Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) have reported associations between PEM and expression of genes coding for adrenergic, metabolic, and immune function. Objectives: To investigate whether PEM is meditated by gene expression in Veterans with GWI. Methods: Veterans with GWI (n = 37) and healthy control Gulf War Veterans (n = 25) provided blood samples before and after 30-min of cycling at 70% of age-predicted heart rate reserve. Relative quantification of gene expression, symptom measurements, and select cardiopulmonary parameters were compared between groups at pre-, 30 minpost-, and 24 hpost-exercise using a doubly multivariate repeated measures analysis of variance (RM-MANOVA). Mediation analyses were used to test indirect effects of changes in gene expression on symptom responses (i.e., PEM) to the standardized exercise challenge. Results: Veterans with GWI experienced large symptom exacerbations following exercise compared to controls (Cohen's d: 1.65; p < 0.05). Expression of ß -actin (ACTB), catechol-O-methyltransferase (COMT), and toll-like receptor 4 (TLR4) decreased in Veterans with GWI at 30 min (p < 0.05) and 24 h post-exercise (p < 0.05). Changes in gene expression did not mediate post-exercise symptom exacerbation in GWI (Indirect Effect Slope Coefficient: 0.06 - 0.02; 95% CI: 0.19, 0.12). Conclusion: An acute bout of moderate intensity cycling reduced the expression of select structural, adrenergic, and immune genes in Veterans with GWI, but the pathophysiological relevance to PEM is unclear.
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Purpose: Mechanisms underlying myofascial temporomandibular disorder (mTMD) are poorly understood. One theory is dysfunction in the central mediation of pain, specifically in enhanced facilitatory pain modulation. Because mechanisms leading to central sensitization may differ for joint and muscle pain, this study of mTMD addressed phenotypic heterogeneity by temporomandibular (TM) joint pain in the examination of quantitative sensory testing (QST). Patients and Methods: The stimulus dependent increase in second pain (temporal summation (TS)) and associated aftersensations (AS) were examined across groups of women with mTMD with TM joint pain and without, and a demographically matched control group. Results: TS was slightly more evident in mTMD without joint pain vs with (p = 0.035), but AS were most robustly persistent in the group with joint pain vs without (p < 0.002). Conclusion: While both subgroups demonstrated evidence of central sensitization relative to controls on one of two measures, differences in QST results, if replicated, may point to possible differences in the mechanisms that yield central sensitization. Alternatively, it may represent methodological artifacts that need to be addressed. Therefore, greater consideration should be given to symptom-based phenotypes in studies examining TS and AS.
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Gulf War Illness (GWI) affects 25-35% of the 1991 Gulf War Veteran (GWV) population. Patients with GWI experience pain, fatigue, cognitive impairments, gastrointestinal dysfunction, skin disorders, and respiratory issues. In longitudinal studies, many patients with GWI have shown little to no improvement in symptoms since diagnosis. The gut microbiome and diet play an important role in human health and disease, and preliminary studies suggest it may play a role in GWI. To examine the relationship between the gut microbiota, diet, and GWI, we conducted an eight-week prospective cohort study collecting stool samples, medications, health history, and dietary data. Sixty-nine participants were enrolled into the study, 36 of which met the case definition for GWI. The gut microbiota of participants, determined by 16S rRNA sequencing of stool samples, was stable over the duration of the study and showed no within person (alpha diversity) differences. Between group analyses (beta diversity) identified statistically significant different between those with and without GWI. Several taxonomic lineages were identified as differentially abundant between those with and without GWI (n = 9) including a greater abundance of Lachnospiraceae and Ruminococcaceae in those without GWI. Additionally, there were taxonomic differences between those with high and low healthy eating index (HEI) scores including a greater abundance of Ruminococcaceae in those with higher HEI scores. This longitudinal cohort study of GWVs found that participants with GWI had significantly different microbiomes from those without GWI. Further studies are needed to determine the role these differences may play in the development and treatment of GWI.
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Microbioma Gastrointestinal , Síndrome del Golfo Pérsico , Veteranos , Microbioma Gastrointestinal/genética , Guerra del Golfo , Humanos , Estudios Longitudinales , Síndrome del Golfo Pérsico/diagnóstico , Estudios Prospectivos , ARN Ribosómico 16S/genéticaRESUMEN
Introduction: This study examined the relationship between cardiorespiratory fitness (CRF) and longitudinal cognitive functioning in a cohort enriched with risk factors for Alzheimer's disease (AD). Methods: A total of 155 enrollees in the Wisconsin Registry for Alzheimer's Prevention completed repeat comprehensive neuropsychological evaluations that assessed six cognitive domains. Peak oxygen consumption (VO2peak) was the primary measure of CRF. Random effects regression was used to investigate the effect of CRF on cognitive trajectories. Results: Higher CRF was associated with slower decline in the cognitive domains of verbal learning and memory (P < .01) and visual learning and memory (P < .042). Secondary analyses indicated that these effects were stronger among men than women, and for noncarriers of the apolipoprotein E ε4 allele. Discussion: Higher CRF was associated with a slower rate of the decline in episodic memory that occurs as a natural consequence of aging in a cohort enriched with risk factors for AD.
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Chronic musculoskeletal pain (CMP) is a significant burden for Persian Gulf War Veterans (GWV), yet the causes are poorly understood. Brain structure abnormalities are observed in GWV, however relationships with modifiable lifestyle factors such as physical activity (PA) are unknown. We evaluated gray matter volumes and associations with symptoms, PA, and sedentary time in GWV with and without CMP. Ninety-eight GWV (10 females) with CMP and 56 GWV (7 females) controls completed T1 weighted magnetic resonance imaging, pain and fatigue symptom questionnaires, and PA measurement via actigraphy. Regional gray matter volumes were analyzed using voxel-based morphometry and were compared across groups using analysis of covariance. Separate multiple linear regression models were used to test associations between PA intensities, sedentary time, symptoms, and gray matter volumes. Family-wise cluster error rates were used to control for multiple comparisons (α=0.05). GWV with CMP reported greater pain and fatigue symptoms, worse mood, and engaged in less moderate-to-vigorous PA and more sedentary time than healthy GWV (all p<0.05). GWV with CMP had smaller gray matter volumes in the bilateral insula and larger volumes in the frontal pole (p<0.05adjusted). Gray matter volumes in the left insula were associated with pain symptoms (rpartial=0.26, -0.29; p<0.05adjusted). No significant associations were observed for either PA or sedentary time (p>0.05adjusted). GWV with CMP had smaller gray matter volumes within a critical brain region of the descending pain processing network and larger volumes within brain regions associated with pain sensation and affective processing which may reflect pain chronification.Significance Statement:The pathophysiology of chronic pain in Gulf War Veterans is understudied and not well understood. In a large sample of Gulf War Veterans, we report Veterans with chronic musculoskeletal pain have smaller gray matter volumes in brain regions associated with pain regulation and larger volumes in regions associated with pain sensitivity compared to otherwise healthy Gulf War Veterans. Gray matter volumes in regions of pain regulation were significantly associated with pain symptoms and encompassed the observed group brain volume differences. These results are suggestive of deficient pain modulation that may contribute to pain chronification.
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BACKGROUND: Cardiopulmonary exercise testing has demonstrated clinical utility in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, to what extent exercise responses are independent of, or confounded by, aerobic fitness remains unclear. PURPOSE: To characterize and compare exercise responses in ME/CFS and controls with and without matching for aerobic fitness. METHODS: As part of the Multi-site Clinical Assessment of ME/CFS (MCAM) study, 403 participants (n = 214 ME/CFS; n = 189 controls), across six ME/CFS clinics, completed ramped cycle ergometry to volitional exhaustion. Metabolic, heart rate (HR), and ratings of perceived exertion (RPE) were measured. Ventilatory equivalent ([Formula: see text], [Formula: see text]), metrics of ventilatory efficiency, and chronotropic incompetence (CI) were calculated. Exercise variables were compared using Hedges' g effect size with 95% confidence intervals. Differences in cardiopulmonary and perceptual features during exercise were analyzed using linear mixed effects models with repeated measures for relative exercise intensity (20-100% peak [Formula: see text]). Subgroup analyses were conducted for 198 participants (99 ME/CFS; 99 controls) matched for age (±5 years) and peak [Formula: see text] (~1 ml/kg/min-1). RESULTS: Ninety percent of tests (n = 194 ME/CFS, n = 169 controls) met standard criteria for peak effort. ME/CFS responses during exercise (20-100% peak [Formula: see text]) were significantly lower for ventilation, breathing frequency, HR, measures of efficiency, and CI and significantly higher for [Formula: see text], [Formula: see text] and RPE (p<0.05adjusted). For the fitness-matched subgroup, differences remained for breathing frequency, [Formula: see text], [Formula: see text], and RPE (p<0.05adjusted), and higher tidal volumes were identified for ME/CFS (p<0.05adjusted). Exercise responses at the gas exchange threshold, peak, and for measures of ventilatory efficiency (e.g., [Formula: see text]) were generally reflective of those seen throughout exercise (i.e., 20-100%). CONCLUSION: Compared to fitness-matched controls, cardiopulmonary responses to exercise in ME/CFS are characterized by inefficient exercise ventilation and augmented perception of effort. These data highlight the importance of distinguishing confounding fitness effects to identify responses that may be more specifically associated with ME/CFS.
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Ejercicio Físico , Síndrome de Fatiga Crónica , Prueba de Esfuerzo , Frecuencia Cardíaca , Humanos , Consumo de Oxígeno/fisiología , Esfuerzo Físico , Aptitud Física , Volumen de Ventilación PulmonarRESUMEN
Introduction: An active lifestyle with regular exercise is thought to decrease or delay the onset of Alzheimer dementia through increasing blood flow to the brain. We examined the mean flow velocity (MFV) and pulsatility index (PI) in the middle cerebral arteries of individuals randomized into two groups-a Usual Physical Activity (UPA) group and an Enhanced Physical Activity (EPA) exercise intervention group-to determine if exercise training is related to changes in cerebral blood flow. Methods: We examined 23 participants, randomized into a UPA group (n=12) and an EPA group (n=11), with transcranial color-coded Doppler (TCCD) and cardiorespiratory fitness (VO2peak, mL/kg/min) testing at baseline and following a 26-week intervention. TCCD was used to measure MFV and PI. Participants in the EPA group completed supervised aerobic exercise training for 26 weeks. Kendall's tau b correlation was used to examine relationships between variables. The Wilcoxon Rank Sum tests were used to examine changes between the UPA and EPA groups. Results: There was no significant change in MFV or PI in the UPA group or the EPA group (p-values >0.05) between baseline and 26 weeks; the change between the UPA and EPA groups was also not significant (p=0.603). There was no evidence of an association between change in VO2peak and change in MFV or PI (all p-values >0.05). Participants in the EPA group significantly increased their VO2peak compared to the UPA group (p=0.027). Conclusion: This study did not demonstrate evidence of a significant change in the MFV in the middle cerebral arteries or evidence of a significant change in the PI between UPA and EPA groups. Future studies should be performed in larger cohorts and should consider use of personalized exercise programs to maximize understanding of how cerebrovascular hemodynamics change in structure and function with exercise for adults at risk for Alzheimer dementia.
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OBJECTIVE: Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are two debilitating, moderately comorbid illnesses in which chronic musculoskeletal pain symptoms are prevalent. These individuals can experience post-exertional malaise (PEM), a phenomenon in which symptom severity is worsened for 24 hours or longer after physical stress, but the pain-related component of PEM is not well characterized. DESIGN: Systematic review and meta-analysis. METHODS: Case-control studies involving adults with ME/CFS or FM and measuring pain symptoms before and after exposure to a standardized aerobic exercise test were included. Hedges' d effect sizes were aggregated with random-effects models, and potential moderators were explored with meta-regression analysis. Results were adjusted for nesting effects with three-level modeling. RESULTS: Forty-five effects were extracted from 15 studies involving 306 patients and 292 healthy controls. After adjusting for nesting effects, we observed a small to moderate effect indicating higher post-exercise pain in patients than in controls (Hedges' d = 0.42; 95% confidence interval [CI]: 0.16-0.67). The mean effect was significantly moderated by pain measurement time point (b = -0.19, z = -2.57, P = 0.01), such that studies measuring pain 8-72 hours after exercise showed larger effects (d = 0.71, 95% CI = 0.28-1.14) than did those measuring pain 0-2 hours after exercise (d = 0.32, 95% CI = 0.10-0.53). CONCLUSIONS: People with ME/CFS and FM experience small to moderate increases in pain severity after exercise, which confirms pain as a component of PEM and emphasizes its debilitating impact in ME/CFS and FM. Future directions include determining mechanisms of pain-related PEM and developing exercise prescriptions that minimize symptom exacerbation in these illnesses.
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Síndrome de Fatiga Crónica , Fibromialgia , Adulto , Ejercicio Físico , Prueba de Esfuerzo , Síndrome de Fatiga Crónica/diagnóstico , Fibromialgia/complicaciones , Humanos , DolorRESUMEN
This study examined 5-year changes in cardiorespiratory fitness, physical activity, and sedentary time in mid-to-late aged adults. Fifty-seven participants completed baseline and follow-up treadmill exercise tests and physical activity monitoring. We observed a 14% decline in fitness (p < 0.001), 12% decrease in physical activity (p = 0.010), and non-significant increase in sedentary time (p = 0.196). Age was negatively associated with 5-year change in physical activity (r = -0.31; p = 0.02) and this decline was strongest among APOE ε4 carriers (g = -0.75). Novelty: Cardiorespiratory fitness and physical activity significantly declined from mid-to-late adulthood, these findings were most pronounced among older adults and those with genetic risk for Alzheimer's disease.
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Capacidad Cardiovascular , Ejercicio Físico/tendencias , Conducta Sedentaria , Acelerometría , Anciano , Apolipoproteína E4/sangre , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
AIMS: The Gulf War Illness programs (GWI) of the United States Department of Veteran Affairs and the Department of Defense Congressionally Directed Medical Research Program collaborated with experts to develop Common Data Elements (CDEs) to standardize and systematically collect, analyze, and share data across the (GWI) research community. MAIN METHODS: A collective working group of GWI advocates, Veterans, clinicians, and researchers convened to provide consensus on instruments, case report forms, and guidelines for GWI research. A similar initiative, supported by the National Institute of Neurologic Disorders and Stroke (NINDS) was completed for a comparative illness, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and provided the foundation for this undertaking. The GWI working group divided into two sub-groups (symptoms and systems assessment). Both groups reviewed the applicability of instruments and forms recommended by the NINDS ME/CFS CDE to GWI research within specific domains and selected assessments of deployment exposures. The GWI CDE recommendations were finalized in March 2018 after soliciting public comments. KEY FINDINGS: GWI CDE recommendations are organized in 12 domains that include instruments, case report forms, and guidelines. Recommendations were categorized as core (essential), supplemental-highly recommended (essential for specified conditions, study types, or designs), supplemental (commonly collected, but not required), and exploratory (reasonable to use, but require further validation). Recommendations will continually be updated as GWI research progresses. SIGNIFICANCE: The GWI CDEs reflect the consensus recommendations of GWI research community stakeholders and will allow studies to standardize data collection, enhance data quality, and facilitate data sharing.
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Elementos de Datos Comunes/normas , Síndrome del Golfo Pérsico , Investigación Biomédica , Humanos , Difusión de la Información , National Institute of Neurological Disorders and Stroke (U.S.) , Síndrome del Golfo Pérsico/etiología , Estados Unidos , United States Department of Veterans Affairs , Salud de los VeteranosRESUMEN
INTRODUCTION: Cardiorespiratory fitness (CRF) may mitigate Alzheimer's disease (AD) progression. This study examined the longitudinal associations of CRF with brain atrophy and cognitive decline in a late-middle-aged cohort of adults at risk for AD. METHODS: One hundred ten cognitively unimpaired adults (66% female, mean age at baseline 64.2 ± 5.7 years) completed a baseline graded treadmill exercise test, two brain magnetic resonance imaging scans (over 4.67 ± 1.17 years), and two to three cognitive assessments (over 3.26 ± 1.02 years). Linear mixed effects models examined the longitudinal associations adjusted for covariates. RESULTS: Participants with higher baseline CRF had slower annual decline in total gray matter volume (P = .013) and cognitive function (P = .048), but not hippocampal volume (P = .426). Exploratory analyses suggested these effects may be stronger among apolipoprotein E ε4 carriers. DISCUSSION: CRF is a modifiable physiological attribute that may be targeted during the preclinical phase of AD in effort to delay disease progression, perhaps most effectively among those with genetic risk.
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AIMS: Chronic widespread musculoskeletal pain (CMP) is a primary condition of Veterans suffering from Gulf War illness. This study evaluated the influence of resistance exercise training (RET) on symptoms, mood, perception of improvement, fitness, and total physical activity in Gulf War Veterans (GWV) with CMP. MAIN METHODS: Fifty-four GWV with CMP were randomly assigned to 16 weeks of RET (n = 28) or wait-list control (n = 26). Supervised exercise was performed twice weekly starting at a low intensity. Outcomes, assessed at baseline, 6, 11 and 17 weeks and 6- and 12-months post-intervention, were: pain, fatigue, mood, sleep quality, perception of improvement, and physical activity via self-report and accelerometry. Muscular strength was assessed at baseline, 8 and 16 weeks. Accelerometer data yielded estimates of time spent in sedentary, light, and moderate-to-vigorous physical activities. Analyses used separate linear mixed models with group and time point as fixed effects. All models, except for perceived improvement, included baseline values as a covariate. KEY FINDINGS: Participants assigned to RET completed 87% of training sessions and exhibited strength increases between 16 and 34% for eight lifts tested (Hedges' g range: 0.47-0.78). The treatment by time interaction for perceived improvement (F1,163 = 16.94, p < 0.001) was characterized by greater perceived improvement since baseline for RET at each time point, until the 12-month follow-up. Effects were not significant for other outcomes (p > 0.05). RET caused no adverse events. SIGNIFICANCE: After 16 weeks of RET, GWV with CMP reported improvements in their condition and exhibited increases in muscular strength, without symptom exacerbation or reductions in total physical activity.