Neuromuscular electrical stimulation to combat cognitive aging in people with spinal cord injury: protocol for a single case experimental design study.

INTRODUCTION: Individuals with spinal cord injury (SCI) can experience accelerated cognitive aging. Myokines (factors released from muscle cells during contractions), such as brain-derived neurotrophic factor (BDNF), are thought to have beneficial effects on cognition. Neuromuscular electrical stimulation (NMES) was shown to elicit a large release of myokines. However, the effects of NMES on cognitive function have not been studied. OBJECTIVE: To present the study protocol for a clinical trial evaluating the effects of NMES aimed at improving cognition and BDNF. METHODS: A replicated randomized three-phases single-case experimental design (SCED) with sequential multiple baseline time series and a single-armed prospective trial will be conducted with 15 adults with chronic SCI (> 12 months after injury) above L1 neurological level undergoing 30-min quadriceps NMES, 3 days per week for 12 weeks. MAIN STUDY ENDPOINTS: Primary endpoint is cognitive performance (assessed by a smartphone test) conducted three times per week during the baseline phase with random duration of 3 to 8 weeks, the intervention phase of 12 weeks, and the follow-up phase of 3 weeks after a no measurement rest period of 12 weeks. Secondary endpoints are changes in BDNF levels and cognitive performance measured before the baseline period, before and after intervention and after a 12 weeks follow-up. CONCLUSION: This will be the first study investigating the effects of 12 weeks NMES on both cognition and BDNF levels in individuals with SCI. The SCED results provide information on individual treatment effect courses which may direct future research. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05822297, 12/01/2023).

Psychometric properties of two instruments assessing catastrophizing and fear-avoidance behavior in mild traumatic brain injury.

OBJECTIVE: Psychometrically sound measures of catastrophizing about symptoms and fear avoidance behavior are needed to further applications of the fear-avoidance model in mild traumatic brain injury (mTBI) for research and clinical purposes. To this end, two questionnaires were adapted (minor), the Postconcussion Symptom Catastrophizing Scale (PCS-CS) and the Fear of Mental Activity Scale (FMA). This study aimed to investigate the factor structure, internal consistency, test-retest reliability, and concurrent and construct validity of two adapted questionnaires in a sample of participants with mTBI compared to participants with orthopedic injury and healthy adults. METHOD: One hundred eighty-five mTBI participants (40% female), 180 participants with orthopedic injury (55% female), and 116 healthy adults (55% female) participated in the study. All participants were assessed at two time points (2 weeks postinjury and 3 months) using self-reported questionnaires. Data were collected using online questionnaires. RESULTS: Findings indicated a three-factor model (magnification, rumination, helplessness) with a higher order factor (catastrophizing) for the PCS-CS and a two-factor model (activity avoidance and somatic focus) for the FMA. The results showed strong internal consistency, good test-retest reliability, and good concurrent and convergent validity for the PCS-CS and FMA across all samples. CONCLUSIONS: This study has shown that the PCS-CS and FMA are psychometrically sound instruments and can be considered for valid and reliable assessment of catastrophizing about postconcussion like symptoms and fear-avoidance beliefs about mental activities. These instruments can be used in research and clinical practice applications of the fear-avoidance model and add to explanations of prolonged recovery after mTBI. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Resistance training's impact on blood biomarkers and cognitive function in older adults with low and high risk of mild cognitive impairment: a randomized controlled trial.

BACKGROUND: The aging brain exhibits a neuroinflammatory state, driven partly by peripheral pro-inflammatory stimuli, that accelerates cognitive deterioration. A growing body of evidence clearly indicates that physical exercise partly alleviates neuroinflammation and positively affects the aging process and cognition. In this randomized controlled trial, we aimed to observe the effect of 12 weeks of resistance training (RT) on peripheral biomarker levels, cognitive function changes and their interrelationship, and explore differences in those exercise-induced changes in older adults with high risk of mild cognitive impairment (MCI) compared to older adults with low risk of MCI. METHODS: Fifty-two participants (aged 60-85 years old, 28 female) were randomly allocated to a 12 week lower limb RT program consisting of two training sessions per week or waiting list control group. The Montreal Cognitive Assessment (MoCA) was used to stratify participants screened as high (< 26/30) or low risk (≥ 26/30) of MCI. We assessed serum Interleukin 6 (IL-6), Insulin-like Growth Factor-1 (IGF-1), and Kynurenine (KYN) levels. Cognitive measurement consisted of and four subtests of Automated Neuropsychological Assessment Metrics (ANAM), the two-choice reaction time, go/no-go, mathematical processing, and memory search test. RESULTS: Twelve weeks of RT improved Go/No-go test results in older adults with high MCI risk. RT did not significantly affect blood biomarkers. However, IGF-1 level increases were associated with improvements in response time on the mathematical processing test in the exercise group, and IL-6 level increases were associated with improvements in response time on the memory search test in the total group of participants. Finally, KYN levels significantly differed between older adults with low and high MCI risk but no significant associations with performance were found. CONCLUSION: Our study results suggest a different effect of RT on inhibitory control between older adults with low compared to high MCI risk. IGF-1 may play a role in the mechanism behind the cognitive benefit of RT and KYN may be a surrogate biomarker for neurodegeneration and cognitive decline.

Resistance exercise effects on hippocampus subfield volumes and biomarkers of neuroplasticity and neuroinflammation in older adults with low and high risk of mild cognitive impairment: a randomized controlled trial.

Physical exercise is suggested to promote hippocampal neuroplasticity by increasing circulating neurotrophic and anti-inflammatory factors. Our aim was to explore the interplay between the effect of progressive resistance exercise on blood biomarker levels, hippocampal neurometabolite levels and hippocampal volume in older adults with a low compared to a high risk of mild cognitive impairment (MCI). Seventy apparently healthy male/female older adults (aged 60-85 years old) were randomly allocated to a 12 week lower limb progressive resistance or no intervention, stratified for low (< 26/30) or high (≥ 26/30) Montreal Cognitive Assessment (MoCA) score, indicating MCI risk. Outcome measures were blood levels of insulin-like growth factor-1 (IGF-1), interleukin-6 (IL-6) or kynurenine (KYN); hippocampal total and subfield volumes of the cornu ammonis 1 (CA1) and 4 (CA4), subiculum, presubiculum, and dentate gyrus measured with magnetic resonance imaging (MRI); and hippocampus neurometabolites including total N-acetylaspartate (NAA), myo-inositol (mIns), and total creatine (Cr) measured with proton magnetic resonance spectroscopy (1H-MRS). We evaluated the intervention effect, cognitive status effect, their interaction and the bivariate relationship between exercise-induced changes between the outcome measures. Higher kynurenine levels (p = 0.015) and lower subiculum volumes (p = 0.043) were found in older adults with high MCI risk compared to older adults with low MCI risk. Exercise-induced CA1 volume changes were negatively correlated with hippocampal tNAA/mIns level changes (r = -0.605, p = 0.006). This study provides valuable insight in the multifactorial processes related to resistance training in older adults with low or high MCI risk.

Hippocampal neurometabolic and structural changes from pre-to post-COVID-19: A case-series study.

BACKGROUND: Neurological complications of the COVID-19 infection may be caused in part by local neurochemical and structural abnormalities that could not be detected during routine medical examinations. We examined within subject neurometabolic and structural brain alterations from pre-to post-COVID-19 in the hippocampal region of three elderly individuals (aged 63-68 years) who had a COVID-19 infection with mild symptoms. Patients were participating in an interventional study in which they were closely monitored at the time they were diagnosed with COVID-19. Patients 1 and 2 just completed 18-20 resistance training sessions prior to their diagnosis. Patient 3 was assigned to a non-training condition in the same study. METHODS: Whole brain magnetic resonance imaging (MRI) images and proton magnetic resonance spectroscopy (1H-MRS) of the left hippocampus were collected before and after infection. Structural and spectroscopic imaging measures post-COVID-19 were contrasted to the pre-COVID-19 measures and were compared with values for Minimal Detectable Change at 95% (MDC95) and 90% (MDC90) confidence from a group of six elderly (aged 60-79 years) without COVID-19 that participated in the same study. RESULTS: After SARS-COV-2 infection, we observed a reduction of glutamate-glutamine (Glx) in Patients 1 and 2 (≥ 42.0%) and elevation of myo-inositol (mIns) and N-acetyl-aspartate (NAA) in Patient 3 (≥ 36.4%); all > MDC90. MRI findings showed increased (Patients 1 and 2) or unchanged (Patient 3) hippocampal volume. CONCLUSIONS: Overall, findings from this exploratory study suggest that mild COVID-19 infection could be associated with development of local neuroinflammation and reduced glutamate levels in the hippocampus. Our 1H-MRS findings may have clinical value for explaining chronic neurological and psychological complaints in COVID-19 long-haulers.

Caregiver burden and impact on COVID-19 patient participation and quality of life one year after ICU discharge - A prospective cohort study.

OBJECTIVES: to investigate changes in caregiver strain, mental health complaints and QoL in caregivers of COVID-19 ICU survivors in the first year after discharge, and their associations with patients' participation and quality of life. METHODS: Post-ICU COVID-19 survivors, needing inpatient rehabilitation and their informal caregivers were included. Caregiver self-administered questionnaires included quality of life, self-rated health, caregiver strain, anxiety and depression symptoms, post-traumatic stress and coping style. Patients' participation in society was assessed and quality of life. RESULTS: 67 patients (78% male) and 57 caregivers (23.6% male) were included. Three months post-ICU, caregivers experienced caregiver strain (32%), anxiety (41%), depressive symptoms (16%) and PTSD (24%). One year post-ICU, rates decreased, still being 11%, 26%, 10% and 5%, respectively. Caregiver anxiety symptoms and self-rated health at three months were associated with worse patient levels of participation and quality of life one year after ICU discharge (p < 0.05). CONCLUSIONS: COVID-19 caregivers experience high levels of mental health complaints one year after a patient's ICU discharge. Furthermore, our results indicate that patient participation levels and quality of life one year after ICU discharge may be negatively associated by caregiver complaints. PRACTICAL IMPLICATIONS: Counselling and routine assessment of emotional complaints and unmet needs of the informal caregiver should be incorporated and addressed in the rehabilitation treatment of (COVID-19) post-ICU patients.

Acceptability, usability and feasibility of experienced sampling method in chronic secondary pain syndromes.

Background: In chronic pain syndromes, symptoms can fluctuate and change over time. Standard questionnaires cannot register these fluctuations. Nonetheless, the experience sampling method (ESM) is developed to collect momentary measurements of everyday complaints, tracing fluctuations in symptoms and disabling factors over time. Although valuable information can be collected in this way, assessment may also be a burden. This study aimed to investigate the acceptability, usability, and feasibility of ESM in chronic secondary pain syndromes, in a single-center study in the Netherlands. Methods: A prospective observational study with repeated measurements was conducted in patients with chronic secondary neuropathic and musculoskeletal pain syndromes, including small fiber neuropathy, spinal cord injury, and rheumatoid disorder. Results: Thirty-four participants were included and filled in the ESM, of whom 19 were diagnosed with small fiber neuropathy, 11 with spinal cord injury, and 4 with a rheumatoid disorder. The mean age was 54.7 ± 13.9 years (range: 23-77) of whom 52.9% were female. In total, 19 participants filled in the general and user-friendliness evaluation about the acceptability and usability of the ESM. The general evaluation showed no influence of ESM on participants' social contacts (mean 1.47, SD 1.12), activities (mean 1.74, SD 1.44), and mood (mean 1.89, SD 1.59). The answers options of ESM were a good representation of the experiences of participants (mean 4.58, SD 1.77). Regarding feasibility, the overall response rate for answering the beep signals of ESM was 44.5% in total. The missing rate per person varied from 13% to 97% with a median of 54.1%. Conclusion: The general evaluation and the user-friendliness revealed sufficient outcomes in favor of the ESM application. ESM seems a promising measurement tool to use in secondary chronic pain syndromes.

Task-oriented arm training for stroke patients based on remote handling technology concepts: A feasibility study.

BACKGROUND: Improving arm-hand skill performance is a major therapeutic target in stroke rehabilitation. Arm-hand rehabilitation may be enriched in content and variation by using technology-assisted training. Especially for people with a severely affected arm, technology-assisted training offers more challenging training possibilities. OBJECTIVE: The aim of this study was to explore the feasibility of ReHab-TOAT, a "Remote Handling Based Task-Oriented Arm Training" approach featuring enriched haptic feedback aimed at improving daily activities and participation. METHODS: Five subacute or chronic stroke patients suffering moderate to severe arm-hand impairments and five rehabilitation therapists participated. All participants received 2 ReHab-TOAT sessions. Outcome measure was a bespoke feasibility questionnaire on user experiences and satisfaction regarding 'motivation', 'individualization of training', 'potential training effects', and 'implementation in rehabilitation' of patients and therapists. RESULTS: Both patients and therapists experienced ReHab-TOAT as being feasible. They found ReHab-TOAT very motivating and challenging. All patients perceived an added value of ReHab-TOAT and would continue the training. Small improvements regarding exercise variability were suggested. CONCLUSION: ReHab-TOAT seems to be a feasible and very promising training approach for arm-hand rehabilitation of stroke patients with a moderately or severely affected arm. Further research is necessary to investigate potential training effects of ReHab-TOAT.

Body fat and components of sarcopenia relate to inflammation, brain volume, and neurometabolism in older adults.

Obesity and sarcopenia are associated with cognitive impairments at older age. Current research suggests that blood biomarkers may mediate this body-brain crosstalk, altering neurometabolism and brain structure eventually resulting in cognitive performance changes. Seventy-four older adults (60-85 years old) underwent bio-impedance body composition analysis, handgrip strength measurements, 8-Foot Up-and-Go (8UG) test, Montreal Cognitive Assessment (MoCA), blood analysis of interleukin-6 (IL-6), kynurenine, and insulin-like growth factor-1 (IGF-1), as well as brain magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS), estimating neurodegeneration and neuroinflammation. Normal fat% or overweight was associated with larger total gray matter volume compared to underweight or obesity in older adults and obesity was associated with higher N-acetylaspartate/Creatine levels in the sensorimotor and dorsolateral prefrontal cortex. Muscle strength, not muscle mass/physical performance, corresponded to lower kynurenine and higher N-acetylaspartate/Creatine levels in the dorsal posterior cingulate and dorsolateral prefrontal cortex. The inflammatory and neurotrophic blood biomarkers did not significantly mediate these body-brain associations. This study used a multimodal approach to comprehensively assess the proposed mechanism of body-brain crosstalk.

Effects of a remote-handling-concept-based task-oriented arm training (ReHab-TOAT) on arm-hand skill performance in chronic stroke: a study protocol for a two-armed randomized controlled trial.

BACKGROUND: Improving arm-hand skill performance is a major therapeutic target in stroke rehabilitation and needs intensive and varied training. However, guided treatment time is limited. Technology can assist in the training of patients, offering a higher intensity and more variety in content. A new task-oriented arm training approach was developed, using a 'Remote Handling concept based' device to provide haptic feedback during the performance of daily living activities (ReHab-TOAT). This study aims to investigate the effects of ReHab-TOAT on patients' arm-hand function and arm-hand skill performance, quality of life of both patients in the chronic phase after stroke and their caregivers and the patients' perception regarding the usability of the intervention. METHODS: A randomized clinical trial was designed. Adult chronic stroke patients suffering from hemiparesis and arm-hand problems, with an Utrechtse Arm-hand Test score of 1-3, will be invited to participate. Participants in the experimental group receive ReHab-TOAT additional to care as usual. ReHab-TOAT contains task-oriented arm training for stroke patients in combination with haptic feedback, generated by a remote handling device. They will train for 4 weeks, 3× per week, 1.5h per day. Participants in the control group will receive no additional therapy apart from care as usual. The Fugl-Meyer Assessment (FMA), measuring participants' motor performance of the affected arm, is used as the primary outcome measure. Secondary outcome measures are arm-hand capacity of the patient (ARAT), perceived arm-hand skill performance (MAL), actual arm-hand skill performance (accelerometry), patients' quality of life (EuoQol-5D) and caregivers' quality of life (CarerQoL). Participants' perception regarding the usability of the intervention, including both the developed approach and technology used, will be evaluated by the System Usability Scale and a questionnaire on the user experience of technology. Measurements will be performed at 1, 2, 3 and 4 weeks pre-intervention (baseline); immediately post-intervention; and 3, 6 and 9 months post-intervention. Statistical analysis includes linear mixed model analysis. DISCUSSION: This study is designed to investigate the evidence regarding the effects of ReHab-TOAT on patients' performance at different levels of the International Classification of Functioning, disability and health (ICF) model, i.e. a framework measuring functioning and disability in relation to a health condition, and to provide insights on a successful development and research process regarding technology-assisted training in co-creation. TRIAL REGISTRATION: Netherlands Trial Register NL9541. Registered on June 22, 2021.

High intensity training improves symptoms of central sensitization at six-month follow-up in persons with chronic nonspecific low back pain: Secondary analysis of a randomized controlled trial.

BACKGROUND: High intensity training (HIT) improves disability and physical fitness in persons with chronic nonspecific low back pain (CNSLBP). However, it remains unclear if HIT affects pain processing and psychosocial factors. OBJECTIVE: To evaluate 1) the effects of HIT on symptoms of central sensitization and perceived stress and 2) the relationship of symptoms of central sensitization and perceived stress with therapy success, at six-month follow-up, in persons with CNSLBP. METHODS: This is a secondary analysis of a previously published randomized controlled trial. Persons with CNSLBP (n = 51, age=43.6y) completed the Central Sensitization Inventory (CSI) and Perceived Stress Scale (PSS) at baseline (PRE) and six months after 12-week of HIT consisting of concurrent exercise therapy (FU). Two groups were formed based on CSI scores (low-CSI/high-CSI). First, linear mixed models were fitted for each outcome, with time and groups as covariates. Multiple comparisons were executed to evaluate group (baseline), time (within-group), and interaction (between-group) effects. Second, correlation and regression analyses were performed to evaluate if baseline and changes in CSI/PSS scores were related to therapy success, operationalized as improvements on disability (Modified Oswestry Disability Index), and pain intensity (Numeric Pain Rating Scale). RESULTS: Total sample analyses showed a decrease in both CSI and PSS. Within-group analyses showed a decrease of CSI only in the high-CSI group and a decrease of PSS only in the low-CSI group. Between-group analyses showed a pronounced decrease favouring high-CSI (mean difference: 7.9; 95%CI: 2.1, 12.7) and no differences in PSS (mean difference: 0.1; 95%CI: -3.0, 3.2). CSI, but not PSS, was weakly related to therapy success. CONCLUSION: HIT improves symptoms of central sensitization in persons with CNSLBP. This effect is the largest in persons with clinically relevant baseline CSI scores. HIT also decreases perceived stress.

Predicting Long-Term Cognitive Impairments in Survivors after Cardiac Arrest: A Systematic Review.

OBJECTIVE: International guidelines recommend early screening for identification of patients who are at risk of long-term cognitive impairments after cardiac arrest. However, information about predictors is not provided. A systematic review of the literature was performed to identify early predictors of long-term cognitive outcome after cardiac arrest. METHODS: Scopus and PubMed were systematically searched to identify studies on early predictors of long-term cognitive outcome in patients after cardiac arrest. The population included adult cardiac arrest survivors and potential early predictors were demographics, early cognitive screening scores, imaging measures, electroencephalographic measures, and levels of blood biomarkers. Two investigators reviewed studies for relevance, extracted data and assessed risk of bias. RESULTS: Five articles were included. Risk of bias was assessed as low or moderate. Most detected longterm cognitive impairments were in the domain of memory. Coma duration (2 studies), early cognitive impairments by the self-developed clinical Bedside Neuropsychological Test Battery (BNTB) screener (2 studies), and high S-100B levels on day 3 (2 studies) were the most prominent identified determinants of cognitive impairment on the group level. On the individual patient level, a score on the BNTB of ≤ 94.5 predicted cognitive impairments at 6 months after cardiac arrest (1 study without external validation). Studies on brain imaging and electroencephalography are lacking. CONCLUSION: Early bedside cognitive screening can contribute to prediction of long-term cognitive impairment after cardiac arrest. Evidence is scarce for S-100B levels and coma duration and absent for measures derived from brain imaging and electroencephalography.

Myokines may target accelerated cognitive aging in people with spinal cord injury: A systematic and topical review.

Persons with spinal cord injury (SCI) can suffer accelerated cognitive aging, even when correcting for mood and concomitant traumatic brain injury. Studies in healthy older adults have shown that myokines (i.e. factors released from muscle tissue during exercise) may improve brain health and cognitive function. Myokines may target chronic neuroinflammation, which is considered part of the mechanism of cognitive decline both in healthy older adults and SCI. An empty systematic review, registered in PROSPERO (CRD42022335873), was conducted as proof of the lack of current research on this topic in people with SCI. Pubmed, Embase, Cochrane and Web of Science were searched, resulting in 387 articles. None were considered eligible for full text screening. Hence, the effect of myokines on cognitive function following SCI warrants further investigation. An in-depth narrative review on the mechanism of SCI-related cognitive aging and the myokine-cognition link was added to substantiate our hypothetical framework. Readers are fully updated on the potential role of exercise as a treatment strategy against cognitive aging in persons with SCI.

Life after COVID-19: the road from intensive care back to living - a prospective cohort study.

OBJECTIVES: The aim of the study was to evaluate recovery of participation in post-COVID-19 patients during the first year after intensive care unit (ICU) discharge. The secondary aim was to identify the early determinants associated with recovery of participation. DESIGN: Prospective cohort study. SETTING: COVID-19 post-ICU inpatient rehabilitation in the Netherlands, during the first epidemic wave between April and July 2020, with 1-year follow-up. PARTICIPANTS: COVID-19 ICU survivors ≥18 years of age needing inpatient rehabilitation. MAIN OUTCOME MEASURES: Participation in society was assessed by the 'Utrecht Scale for Evaluation of Rehabilitation-Participation' (USER-P) restrictions scale. Secondary measures of body function impairments (muscle force, pulmonary function, fatigue (Multidimensional Fatigue Inventory), breathlessness (Medical Research Council (MRC) breathlessness scale), pain (Numerical Rating Scale)), activity limitations (6-minute walking test, Patient reported outcomes measurement information system (PROMIS) 8b), personal factors (coping (Utrecht Proactive Coping Scale), anxiety and depression (Hospital Anxiety and Depression Scale), post-traumatic stress (Global Psychotrauma Screen-Post Traumatic Stress Disorder), cognitive functioning (Checklist for Cognitive Consequences after an ICU-admission)) and social factors were used. STATISTICAL ANALYSES: linear mixed-effects model, with recovery of participation levels as dependent variable. Patient characteristics in domains of body function, activity limitations, personal and social factors were added as independent variables. RESULTS: This study included 67 COVID-19 ICU survivors (mean age 62 years, 78% male). Mean USER-P restrictions scores increased over time; mean participation levels increasing from 62.0, 76.5 to 86.1 at 1, 3 and 12 months, respectively. After 1 year, 50% had not fully resumed work and restrictions were reported in physical exercise (51%), household duties (46%) and leisure activities (29%). Self-reported complaints of breathlessness and fatigue, more perceived limitations in daily life, as well as personal factors (less proactive coping style and anxiety/depression complaints) were associated with delayed recovery of participation (all p value <0.05). CONCLUSIONS: This study supports the view that an integral vision of health is important when looking at the long-term consequence of post-ICU COVID-19. Personal factors such as having a less proactive coping style or mental impairments early on contribute to delayed recovery.

Living with small fiber neuropathy: insights from qualitative focus group interviews.

OBJECTIVE: Small fiber neuropathy (SFN) is characterized by chronic neuropathic pain and autonomic dysfunction. Currently, symptomatic pharmacological treatment is often insufficient and frequently causes side effects. SFN patients have a reduced quality of life. However, little is known regarding whether psycho-social variables influence the development and maintenance of SFN-related disability and complaints. Additional knowledge may have consequences for the treatment of SFN. For example, factors such as thinking, feeling, and behavior are known to play roles in other chronic pain conditions. The aim of this study was to obtain further in-depth information about the experience of living with SFN and related chronic pain. METHODS: Fifteen participants with idiopathic SFN participated in a prospective, semi-structured, qualitative, focus group interview study. The focus groups were audio-recorded, transcribed, and analyzed cyclically after each interview. RESULTS: The following main themes were identified: "pain appraisal", "coping", "social, work, and health environment", and "change in identity". Catastrophic thoughts and negative emotions were observed. Living with SFN resulted in daily limitations and reduced quality of life. CONCLUSIONS: Given the results, it can be concluded that an optimal treatment should include biological, psychological, and social components.

A change of perspective? An explorative study on why patients may not subjectively report cognitive impairments after a cardiac arrest.

AIM: Cardiac arrest survivors are at risk of long-term cognitive impairment. Patients with cognitive impairments do not always have cognitive complaints and vice versa. Not reporting cognitive complaints could be caused by a lack of awareness. We hypothesized that caregivers report more cognitive failures than patients, indicating patients' lack of insight into cognitive functioning. METHODS: This is a secondary analysis of the Activity and Life After Survival of Cardiac Arrest study on survivors of cardiac arrest and their caregivers. They were assessed at two weeks, three months, and one year after cardiac arrest. At each time point, the patient and the caregiver filled out the cognitive failure questionnaire (CFQ) regarding the patient. We analysed the correlation, intraclass correlation, and self-proxy discrepancy between patients and caregivers on the CFQ over time. RESULTS: One-hundred-and-nineteen cardiac arrest survivors (mean age = 60, 85 % male) and their caregivers were included. The CFQ scores of the patients and caregivers were equally low. The correlation (T1 r = 0.31; T2 r = 0.40; T3 r = 0.55) and intraclass correlation (T1 r = 0.48; T2 r = 0.56; T3 r = 0.71) between patient and caregiver increased over time. CONCLUSION: This study does not support a lack of awareness of cognitive impairments by long-term cardiac arrest survivors. Future research may focus on alternative explanations for why patients have less cognitive complaints than expected based on the frequency of cognitive impairments. Possible explanations include a response shift.

Exploring the feasibility of a network of organizations for pain rehabilitation: What are the lessons learned?

BACKGROUND AND AIMS: Integration of care is lacking for chronic musculoskeletal pain patients. Network Pain Rehabilitation Limburg, a transmural health care network, has been designed to provide integrated rehabilitation care from a biopsychosocial perspective to improve patients' levels of functioning. This feasibility study aims to provide insight into barriers and facilitators for the development, implementation, and transferability. METHODS: This study was conducted with a three-phase iterative and incremental design from October 2017 to October 2018. The network comprises two rehabilitation practices, and three local primary care networks, with a general practitioner together with, a mental health practice nurse, and a physiotherapist or exercise therapist. These stakeholders with a random sample of participating patients took part in evaluations, consisting of interviews, focus groups, and observations. Field notes and observations were recorded during meetings. The Consolidated Framework for Implementation Research guided data collection and analysis. Results were used to refine the next phase. RESULTS: According to health care professionals, guidelines and treatment protocols facilitate consistency and transparency in collaboration, biopsychosocial language, and treatment. One mentioned barrier is the stigmatization of chronic pain by the general population. In regular care, approaches are often more biomedical than biopsychosocial, causing patients to resist participating. The current organization of health care acts as a barrier, complicating implementation between and within practices. Health care professionals were enthusiastic about the iterative, bottom-up development. A critical mass of participating organizations is needed for proper implementation. CONCLUSION: Network Pain Rehabilitation Limburg is feasible in daily practice if barriers are overcome and facilitators of development, implementation, and transferability are promoted. These findings will be used to refine Network Pain Rehabilitation Limburg. A large-scale process and effect evaluation will be performed. Our implementation strategies and results may assist other health care organizations aspiring to implement a transmural network using a similar model. TRAIL REGISTRATION: Registration number: NTR6654 or https://trialsearch.who.int/Trial2.aspx?TrialID=NTR6654.

Inflammatory Blood Biomarker Kynurenine Is Linked With Elevated Neuroinflammation and Neurodegeneration in Older Adults: Evidence From Two 1H-MRS Post-Processing Analysis Methods.

Rationale and Objectives: Pro-inflammatory processes have been argued to play a role in conditions associated with cognitive decline and neurodegeneration, like aging and obesity. Only a limited number of studies have tried to measure both peripheral and central biomarkers of inflammation and examined their interrelationship. The primary aim of this study was to examine the hypothesis that chronic peripheral inflammation would be associated with neurometabolic changes that indicate neuroinflammation (the combined elevation of myoinositol and choline), brain gray matter volume decrease, and lower cognitive functioning in older adults. Materials and Methods: Seventy-four older adults underwent bio-impedance body composition analysis, cognitive testing with the Montreal Cognitive Assessment (MoCA), blood serum analysis of inflammatory markers interleukin-6 (IL-6) and kynurenine, magnetic resonance imaging (MRI), and proton magnetic resonance spectroscopy (1H-MRS) of the brain. Neurometabolic findings from both Tarquin and LCModel 1H-MRS post-processing software packages were compared. The regions of interest for MRI and 1H-MRS measurements were dorsal posterior cingulate cortex (DPCC), left hippocampal cortex (HPC), left medial temporal cortex (MTC), left primary sensorimotor cortex (SM1), and right dorsolateral prefrontal cortex (DLPFC). Results: Elevated serum kynurenine levels were associated with signs of neuroinflammation, specifically in the DPCC, left SM1 and right DLPFC, and signs of neurodegeneration, specifically in the left HPC, left MTC and left SM1, after adjusting for age, sex and fat percentage (fat%). Elevated serum IL-6 levels were associated with increased Glx levels in left HPC, left MTC, and right DLPFC, after processing the 1H-MRS data with Tarquin. Overall, the agreement between Tarquin and LCModel results was moderate-to-strong for tNAA, tCho, mIns, and tCr, but weak to very weak for Glx. Peripheral inflammatory markers (IL-6 and kynurenine) were not associated with older age, higher fat%, decreased brain gray matter volume loss or decreased cognitive functioning within a cohort of older adults. Conclusion: Our results suggest that serum kynurenine may be used as a peripheral inflammatory marker that is associated with neuroinflammation and neurodegeneration, although not linked to cognition. Future studies should consider longitudinal analysis to assess the causal inferences between chronic peripheral and neuroinflammation, brain structural and neurometabolic changes, and cognitive decline in aging.

The Influence of Exercise Intensity on Psychosocial Outcomes in Musculoskeletal Disorders: A Systematic Review.

CONTEXT: Psychosocial parameters play an important role in the onset and persistence of chronic musculoskeletal disorders (CMSDs). Exercise therapy is a valuable therapeutic modality as part of CMSD rehabilitation. Hereby, exercise intensity is an important factor regarding changes in pain and disability in multiple CMSDs. However, the impact of exercise intensity on psychosocial outcomes remains poorly explored. OBJECTIVE: To identify the effects of different modes of exercise intensity on psychosocial outcomes in persons with CMSDs. DATA SOURCES: A systematic search was conducted up to November 2020 using the following databases: PubMed/MEDline, PEDro, Cochrane Library, and Web of Science. STUDY SELECTION: Studies reporting exercise therapy in CMSDs with a predefined display of exercise intensity and an evaluation of at least 1 psychosocial outcome were included. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 2a. DATA EXTRACTION: Data regarding demographics, exercise intensity, and psychosocial outcomes were included in a descriptive analysis. Methodological quality was assessed using the PEDro scale and Critical Appraisal Skills Programme (CASP) checklist. RESULTS: A total of 22 studies, involving 985 participants (with fibromyalgia, chronic low back pain, knee osteoarthritis, psoriatic arthritis, and axial spondyloarthritis) were included (mean PEDro score = 5.77/10). The most common psychosocial outcomes were quality of life (QoL) (n = 15), depression (n = 10), and anxiety (n = 9). QoL improved at any exercise intensity in persons with fibromyalgia. However, persons with fibromyalgia benefit more from exercising at low to moderate intensity regarding anxiety and depression. In contrast, persons with chronic low back pain benefit more from exercising at a higher intensity regarding QoL, anxiety, and depression. Other CMSDs only showed limited or conflicting results regarding the value of certain exercise intensities. CONCLUSION: Psychosocial outcomes are influenced by the intensity of exercise therapy in fibromyalgia and chronic low back pain, but effects differ across other CMSDs. Future research is necessary to determine the exercise intensity that yields optimal exercise therapy outcomes in specific CMSDs.

Exerkines and long-term synaptic potentiation: Mechanisms of exercise-induced neuroplasticity.

Physical exercise may improve cognitive function by modulating molecular and cellular mechanisms within the brain. We propose that the facilitation of long-term synaptic potentiation (LTP)-related pathways, by products induced by physical exercise (i.e., exerkines), is a crucial aspect of the exercise-effect on the brain. This review summarizes synaptic pathways that are activated by exerkines and may potentiate LTP. For a total of 16 exerkines, we indicated how blood and brain exerkine levels are altered depending on the type of physical exercise (i.e., cardiovascular or resistance exercise) and how they respond to a single bout (i.e., acute exercise) or multiple bouts of physical exercise (i.e., chronic exercise). This information may be used for designing individualized physical exercise programs. Finally, this review may serve to direct future research towards fundamental gaps in our current knowledge regarding the biophysical interactions between muscle activity and the brain at both cellular and system levels.