Nivel Corona Cohort: A description of the cohort and methodology used for combining general practice electronic records with patient reported outcomes to study impact of a COVID-19 infection.

AIM: A population-based COVID-19 cohort was set up in the Netherlands to gain comprehensive insight in the short- and long-term effects of COVID-19 in the general population. The present study aims to describe the methodology and infrastructure used to recruit individuals with COVID-19, and the representativeness of the population-based cohort. The second aim was to characterize the population by description of their symptoms and health care usage during the acute COVID-19 phase. METHOD: The starting point of the set-up of the cohort was to recruit participants in routinely recorded, general practice electronic health records (EHR) data, which are sent to the Netherlands Institute for Health Services Research Primary Care Database (Nivel-PCD) on a weekly basis. Patients registered with COVID-19 were flagged in the Nivel-PCD based on their COVID-19 diagnoses. Flagged patients were invited for participation by their general practitioner via a trusted third party. Participating patients received a series of four questionnaires over the duration of one year allowing for a combination of data from patient reported outcomes and EHRs. RESULTS: In this study, results from the first questionnaire are used. The Nivel Corona Cohort consists of 442 participants and is population-based, containing a complete image of severity of symptoms from patients with none or hardly any symptoms to those who were hospitalized due to the COVID-19. The five most prevalent symptoms during the acute COVID-19 phase were fatigue (90.5%), reduced condition (88.2%), coughing/sneezing/stuffy nose (79.3%), headache (75.4%), and myalgia (66.7%). CONCLUSION: The population-based Nivel Corona Cohort provides ample opportunities for future studies to gain comprehensive insight in the short- and long-term effects of COVID-19 by combining patients' perspectives and clinical parameters via the EHRs within a long-term follow-up of the cohort.

Patient-Reported Outcome Measures for Assessing Dual-Task Performance in Daily Life: A Review of Current Instruments, Use, and Measurement Properties.

The patient perspective of dual-task (DT) impairment in real life is unclear. This review aimed (i) to identify patient-reported outcome measures (PROMs) on DT and evaluate their measurement properties and (ii) to investigate the usage of PROMs for the evaluation of DT difficulties. A systematic literature search was conducted using PubMed and Web of Science from inception to March 2022. Methodological quality was evaluated using the COSMIN checklist. Six studies examined the measurement properties of DT PROMs. Nine studies used DT PROMs as the outcome measure. Five PROMs were identified, including the Divided Attention Questionnaire (DAQ), Dual-Task-Impact on Daily-life Activities Questionnaire (DIDA-Q), a Questionnaire by Cock et al. (QOC), Dual-Tasking Questionnaire (DTQ), and Dual-Task Screening-List (DTSL). Fourteen measurement properties were documented: five (35.7%) rated quality as "sufficient", six (42.8%) "insufficient", and three (21.4%) "indeterminate". The quality of evidence for each measurement property ranged from very low to high. While DT performance is investigated in many populations, the use of PROMs is still limited, although five instruments are available. Currently, due to insufficient data, it is not possible to recommend a specific DT PROM in a specific population. An exception is DIDA-Q, which has the highest quality of measurement properties in people with multiple sclerosis.

Embodied learning in multiple sclerosis using melodic, sound, and visual feedback: a potential rehabilitation approach.

Given the prevalence of motor and cognitive functions in persons with multiple sclerosis (PwMS), we proposed that the theoretical framework of embodiment could provide a rehabilitation avenue to train these functions as one functional unit. PwMS (n = 31) and age- and gender-matched healthy controls (n = 30) underwent an embodied learning protocol. This involved learning a cognitive sequence while performing it through bodily stepping movement under three feedback conditions (melody, sound, and visual). Cognitive and movement performance was assessed by a delayed recall 15 min after undergoing the embodied learning protocol. Half of participants correctly recalled the sequence in all three conditions, while 70% of healthy controls achieved correct recall within the melody condition. Balance impairment predicted the speed of executing the sequence irrespective of learning, most apparent in the melody condition. Information processing speed predicted the speed of executing the sequence in the melody and sound conditions between participants as well as over time. Those who learned performed the sequence faster in the melody condition only and overall were faster over time. We propose how embodied learning could expand the current context of rehabilitation of cognitive and motor control in PwMS.

Changes in Gait Characteristics During and Immediately After the 6-Minute Walk Test in Persons With Multiple Sclerosis: A Systematic Review.

OBJECTIVE: There is limited information about gait patterns during prolonged walking in people with multiple sclerosis (PwMS). The aim of this review was to report on gait metrics during and immediately after the 6-Minute Walk Test (6MWT) in PwMS with different levels of disability. METHODS: The systematic search was performed in 3 databases (PubMed, Web of Science, and SCOPUS) using keywords related to multiple sclerosis and 6MWT. Studies that reported on quantitative gait outcomes before and after the 6MWT or multiple time points during the 6MWT were included. The Hedges g effect size (ES) was calculated to determine the magnitude of change in each gait parameter. RESULTS: Fourteen studies (n = 534 PwMS; n = 166 healthy controls) were eligible. Five studies investigated gait parameters prior to and immediately after the 6MWT. Nine studies collected gait measures during the 6MWT. Speed (ES = -0.43 to 0.19), cadence (ES = -0.46 to 0.16), step length (ES = -0.46 to 0.14), stability (ES = -0.35 to 0.33), and regularity (ES = -0.25 to -0.15) decreased in most studies. In the majority of included studies, step time (ES = 0 to 0.35), stance period (ES = 0.12 to 0.58), double support phase (ES = 0.03 to 0.62), variability (ES = -0.19 to 1.13), and asymmetry (ES = -0.79 to 0.62) increased following the 6MWT. The kinetic and kinematic (mainly in dorsiflexion angle [ES = -0.08 to -0.36]) features of gait were also negatively changed after 6 minutes of walking. Walking speed, cadence, step length, stride length, and stride time after 6MWT at a comfortable speed all increased. Changes in the majority of spatiotemporal parameters were more pronounced in PwMS with moderate-to-severe disability compared with PwMS with mild disability. CONCLUSION: Most quantitative gait parameters deteriorated during the 6MWT, especially in PwMS with moderate-to-severe disability. IMPACT: The deterioration of gait patterns should be considered when designing therapeutic interventions to increase sustained walking capacity.

Motor sequence learning in a goal-directed stepping task in persons with multiple sclerosis: a pilot study.

Motor sequence learning in persons with multiple sclerosis (pwMS) and healthy controls (HC) under implicit or explicit learning conditions has not yet been investigated in a stepping task. Given the prevalent cognitive and mobility impairments in pwMS, this is important in order to understand motor learning processes and optimize rehabilitation strategies. Nineteen pwMS (the Expanded Disability Status Scale = 3.4 ± 1.2) and 18 HC performed a modified serial reaction time task by stepping as fast as possible on a stepping tile when it lit up, either with (explicit) or without (implicit) knowledge of the presence of a sequence beforehand. Motor sequence learning was studied by examining response time changes and differences between sequence and random blocks during the learning session (acquisition), 24 h later (retention), and in three dual-task (DT) conditions at baseline and retention (automaticity) using subtracting sevens, verbal fluency, and vigilance as concurrent cognitive DTs. Response times improved and were lower for the sequenced compared with the random blocks at the post- and retention tests (P's < 0.001). Response times during DT conditions improved after learning, but DT cost improved only for the subtracting sevens DT condition. No differences in learning were observed between learning conditions or groups. This study showed motor sequence learning, by acquisition and retention, in a stepping task in pwMS with motor impairments, to a similar degree as HC and regardless of learning conditions. Whether automaticity increased remains unclear.

Cognitive-motor Interference in Individuals With a Neurologic Disorder: A Systematic Review of Neural Correlates.

BACKGROUND: Performing a cognitive task and a motor task simultaneously is an everyday act that can lead to decreased performance on both tasks. OBJECTIVE: To provide insight into the neural correlates associated with cognitive-motor dual tasking in individuals with a neurologic disorder. METHOD: We searched the PubMed and Web of Science databases for studies that had been published up to January 16th, 2019. Studies investigating the neural correlates of cognitive-motor dual task performance in individuals with a variety of neurologic disorders were included, independently from whether the study included healthy controls. Clinical and imaging data were abstracted for the comparison between single tasks and a dual task in the individuals with a neurologic disorder and for the comparison between the healthy controls and the individuals with a neurologic disorder. RESULTS: Eighteen studies met the inclusion criteria. Study populations included individuals with Parkinson disease, multiple sclerosis, mild cognitive impairment, Alzheimer disease, traumatic brain injury, and stroke. Neuroimaging types used to study the neural correlates of cognitive-motor dual tasking during upper limb or gait tasks included fMRI, functional near-infrared spectroscopy, EEG, and PET. CONCLUSION: Despite large heterogeneity in study methodologies, some recurrent patterns were noted. Particularly, in neurologic patients, an already higher brain activation during single tasks was seen compared with healthy controls, perhaps compromising the patients' ability to further adapt brain activation with increasing load during dual tasking and resulting in reduced behavioral dual task performance.

Differential effects and discriminative validity of motor and cognitive tasks varying in difficulty on cognitive-motor interference in persons with multiple sclerosis.

BACKGROUND: Cognitive-motor interference (CMI) has been well recognized in persons with multiple sclerosis (pwMS); however, there are limited data on effects of task difficulty. OBJECTIVE: Examine (1) the effects of motor and cognitive tasks varying in difficulty on the magnitude of CMI and (2) the discriminative validity of CMI between pwMS and healthy controls (HC). METHODS: Nine cognitive-motor dual-task (DT) conditions (combinations of three cognitive and three walking tasks) were examined. Outcome measures were DT-performance and dual-task cost (DTC) of gait parameters and correct answers. Task differences and overall group-effects were analysed by mixed model analysis, plus the Wilcoxon signed-rank tests or multivariate analysis of variances (MANOVAs), respectively. RESULTS: Task effects were examined in 82 pwMS (Expanded Disability Status Scale (EDSS): 3.3 ± 1.0) and discriminative validity in a subsample (35 pwMS and 33 HC). Motor-DTC and DT-performance were affected by difficulty of both the cognitive task (p < 0.001) and the walking condition (p ⩽ 0.002), while cognitive-DTC only varied between cognitive tasks with a large difference in difficulty (p ⩽ 0.005) and not between walking conditions (p ⩾ 0.125). None of the DTCs differed between groups. CONCLUSION: CMI, and especially motor performance, is affected by difficulty of the DT. Although pwMS performed worse on the tasks than HC, none of the DT-conditions showed a discriminative DTC.

Comparing 16 Different Dual-Tasking Paradigms in Individuals With Multiple Sclerosis and Healthy Controls: Working Memory Tasks Indicate Cognitive-Motor Interference.

Background: Cognitive-motor interference (CMI) is measured by dual-tasking (DT), which involves motor and cognitive tasks. There is no consensus as to whether CMI is present in multiple sclerosis (MS). Objectives: We investigated the effects of 16 DT conditions by measuring motor complexity, cognitive domain, and task difficulty. Method: In total, 40 persons with MS (pwMSs) with Expanded Disease Status Scale (EDSS) 3.2 ± 1.7 and 31 age- and sex-matched healthy controls (HCs) completed 2 single walking, 8 single cognitive, and 2 complex walking tasks and 16 cognitive-motor DT. The main outcomes were mean values of gait velocity and the percentage change from single to DT (motor DT costs, mDTCs) and mean values of cognitive task accuracy and the percentage changes (cognitive DTC, cDTC). Results: Two-way analyses of variance showed the main effect of cognitive task yielded an F ratio of F (4, 268) = 72.35, p < 0.01, for mean gait velocity, and an F ratio of F (4, 304) = 17.12, p < 0.001, for mDTC, indicating that the mean velocity was significantly lower and the mDTC significantly higher for DS_B (mean = 1.27, SD = 0.03, and mean = 13.52, SD = 1.28, respectively). The main effect of cognitive task yielded an F ratio of F (4, 116) = 84.32, p < 0.001, with the lowest average accuracy for DS_B (mean = 43.95, SD = 3.33); no effect was found for cDTC. In pwMSs, the EDSS accounted for 28% (F = 13.65, p = 0.001) of variance in a model predicting the highest mDTC. Conclusions: Overall, among different cognitive tasks added, the Digit Span backward was the most interfering cognitive task over gait velocity and accuracy. The effect was similar independently from the motor complexity and the group. PwMSs and HCs behaved in a similar manner at all motor complexity levels and during all cognitive task.

Effects of a 10-week multimodal dance and art intervention program leading to a public performance in persons with multiple sclerosis - A controlled pilot-trial.

BACKGROUND: Dance therapy is increasingly reported in neurological diseases for improving several motor and cognitive functions, but was mostly studied in partner dance. No individual choreo-based dance program has ever been reported in MS. OBJECTIVES: The aim of this pilot study is to investigate effects of a ten-week choreo-based dance intervention on different impairments in MS. PARTICIPANTS: Seventeen participants with MS were allocated to a dance group (DG) or an art group (AG) for a ten-week intervention program, with a public live performance at the end of the intervention. METHODS: The DG received choreo-based dance courses twice a week for 90 min, while the active control AG weekly contributed to the production by painting, music, spoken word and photo- or videography. Measurements for fatigue and fatigability, physical capacity and coordination, sensory function, cognitive capacity, quality of life and dual task performance took place before and after the intervention. Differences were analysed with Wilcoxon Signed Rank test. RESULTS: Both groups improved significantly on executive cognitive performance during dual task and fatigue. Only the DG improved significantly on functional lower limb strength, hand function, coordination, self-reported balance and walking, and showed a trend towards improving on cognition (PASAT). The AG showed significant improvements in on cognitive function (SDMT). CONCLUSION: A ten-week multimodal dance intervention has positive effects on impact of fatigue, physical capacity and coordination, and cognitive performance during a dual task. Larger samples, follow-up measurements and research in different disability groups is recommended.

Design, Development, and Testing of an App for Dual-Task Assessment and Training Regarding Cognitive-Motor Interference (CMI-APP) in People With Multiple Sclerosis: Multicenter Pilot Study.

BACKGROUND: Dual tasking constitutes a large portion of most activities of daily living; in real-life situations, people need to not only maintain balance and mobility skills, but also perform other cognitive or motor tasks at the same time. Interest toward dual-task training (DTT) is increasing as traditional interventions may not prepare patients to adequately face the challenges of most activities of daily living. These usually involve simultaneous cognitive and motor tasks, and they often show a decline in performance. Cognitive-motor interference (CMI) has been investigated in different neurological populations, but limited evidence is present for people with multiple sclerosis (MS). The use of computerized tools is mandatory to allow the application of more standardized assessment and rehabilitation intervention protocols and easier implementation of multicenter and multilanguage studies. OBJECTIVE: To describe the design and development of CMI-APP, an adaptive and interactive technology tablet-based app, and to present the preliminary results of a multicenter pilot study involving people with MS performed in several European centers for evaluating the feasibility of and adherence to a rehabilitation program based on CMI-APP. METHODS: CMI-APP includes user-friendly interfaces for personal data input and management, assessment of CMI, and DTT. A dedicated team developed CMI-APP for Android tablets above API level 14 (version 4.0), using C# as the programming language and Unity and Visual Studio as development tools. Three cognitive assessment tests for working memory, information processing speed, and sustained attention and four motor assessment tests for walking at different difficulty levels were implemented. Dual cognitive-motor tasks were performed by combining single cognitive and motor tasks. CMI-APP implements exercises for DTT involving the following 12 cognitive functions: sustained attention, text comprehension, verbal fluency, auditory discrimination, visual discrimination, working memory, information processing speed, auditory memory, visual memory, verbal analog reasoning, visual analog reasoning, and visual spatial planning, which can be performed during walking or stepping on the spot. Fifteen people with MS (mean age 52.6, SD 8.6 years; mean disease duration 9.4, SD 8.4 years; mean Expanded Disability Status Scale score 3.6, SD 1.1) underwent DTT (20 sessions). Adherence to the rehabilitation program was evaluated according to the percentage of performed sessions, perceived exertion during the training (Borg 15-point Ratings of Perceived Exertion [RPE] Scale), and subjective experience of the training (Intrinsic Motivation Inventory [IMI]). RESULTS: The adherence rate was 91%. DTT was perceived as "somewhat difficult" (mean RPE Scale score 12.6, SD 1.9). IMI revealed that participants enjoyed the training and felt that it was valuable and, to some extent, important, without feelings of pressure. They felt competent, although they did not always feel they could choose the exercises, probably because the therapist chose the exercises and many exercises had few difficulty levels. CONCLUSIONS: CMI-APP is safe, highly usable, motivating, and well accepted for DTT by people with MS. The findings are fundamental for the preparation of future large-sample studies examining CMI and the effectiveness of DTT interventions with CMI-APP in people with MS.

Day-to-day reliability, agreement and discriminative validity of measuring walking-related performance fatigability in persons with multiple sclerosis.

BACKGROUND: Day-to-day reliability and cut-off values to detect abnormal walking fatigability (WF) remain to be investigated in persons with multiple sclerosis (pwMS). METHODS: In all, 49 pwMS (mean Expanded Disability Status Scale (EDSS) ± standard deviation (SD): 3.3 ± 1.9) and 28 matched healthy controls (HC) performed the six-minute walking test (6MWT) on two different days to determine day-to-day reliability (intraclass correlation coefficient (ICC)) and limits of agreement (LOA) for five different equations of WF. OBJECTIVE: To examine day-to-day reliability, agreement and discriminative validity for measuring WF. RESULTS AND CONCLUSION: WF expressed as the ratio between the first and sixth minute had the best day-to-day reliability (ICC's range of 0.76-0.95 and 0.60-0.86, respectively) in both pwMS and HC, while LOA were 15% and 7%, respectively. Ecological validity and clinical importance should be further investigated.

Structured Cognitive-Motor Dual Task Training Compared to Single Mobility Training in Persons with Multiple Sclerosis, a Multicenter RCT.

The aim was to compare the effectiveness of dual-task training (DTT) compared to single mobility training (SMT) on dual-task walking, mobility and cognition, in persons with Multiple Sclerosis (pwMS). Forty pwMS were randomly assigned to the DTT or SMT groups. The DTT-group performed dual-task exercises using an interactive tablet-based application, while the SMT-group received conventional walking and balance exercises. Both interventions were supervised and identical in weeks (8) and sessions (20). Nine cognitive-motor dual-task conditions were assessed at baseline, after intervention and at 4-weeks follow-up (FU). The dual-task cost (DTC), percentage change of dual-task performance compared to single-task performance, was the primary outcome. Mobility and cognition were secondarily assessed. Mixed model analyses were done with group, time and the interaction between group and time as fixed factors and participants as random factors. Significant time by group interactions were found for the digit-span walk and subtraction walk dual-task conditions, with a reduction in DTC (gait speed) for the DTT maintained at FU. Further, absolute dual-task gait speed during walking over obstacles only improved after the DTT. Significant improvements were found for both groups in various motor and cognitive measures. However, the DTT led to better dual-task walking compared to the SMT.

Test-Retest Reliability of Cognitive-Motor Interference Assessments in Walking With Various Task Complexities in Persons With Multiple Sclerosis.

Background. Simultaneous execution of motor and cognitive tasks can result in worsened performance on one or both tasks, indicating cognitive-motor interference (CMI). A growing amount of research on CMI in persons with multiple sclerosis (pwMS) is observed. However, psychometric properties of dual-task outcomes have been scarcely reported. Objective. To investigate the between-day test-retest reliability of the motor and cognitive dual-task costs (DTCs) during multiple CMI test conditions with various task complexities in pwMS and matched healthy controls (HCs). Methods. A total of 34 pwMS (Expanded Disability Status Scale score 3.0 ± 0.8) and 31 HCs were tested and retested on 3 single cognitive, 4 single motor, and 12 cognitive-motor dual tasks. Cognitive tasks included serial subtraction by 7, titrated digit span backward, and auditory vigilance. Motor tasks were walking at self-selected speed, over obstacles, crisscross, and while carrying a water-filled cup. Outcome measures were cognitive and motor DTC, calculated as percentage change of dual-task performance compared with single-task performance. Intraclass correlations (ICCs) and Spearman correlation coefficients were calculated as appropriate. Results. For DTCmotor of gait speed, ICCs ranged from 0.45 to 0.81 and Spearman correlations from 0.74 to 0.82. For DTCcognitive, ICCs ranged from -0.18 to 0.49 and Spearman correlations from -0.28 to 0.26. Reliability depended on the type of motor and cognitive task. Conclusion. Reliability of the DTCmotor was, overall, good, whereas that of the DTCcognitive was poor. The "walking" and "cup" dual-task conditions were the most reliable regardless of the integrated cognitive task.

Cognitive-motor interference in persons with multiple sclerosis during five upper limb motor tasks with different complexity.

BACKGROUND: Cognitive-motor interference in multiple sclerosis has been well examined during walking, but not during upper limb (UL) performance. OBJECTIVES: To examine the dual-task cost (DTC) in persons with multiple sclerosis (pwMS) and healthy controls (HC) in various type and complexity of UL motor tasks. METHOD: In total, 30 pwMS without major UL impairment and 30 HC performed five different UL tasks, in single condition and combined with the phonemic word list generation task. The percent change in performances was evaluated by the motor, cognitive, and combined DTC. The motor tasks consisted of four unimanual (sustained hand grip strength, box-and-block test, Purdue pegboard test, finger tapping task) and one bimanual task (Purdue pegboard test). Group and task differences were analyzed with unpaired and paired t-tests, respectively, and overall effect with a multivariate analysis of variance. RESULTS: The motor DTC ranged between 10% (Purdue pegboard bimanual) and 35% (box-and-block test). The cognitive DTC ranged between -8% (finger tapping test) and +21% (bimanual Purdue pegboard). The magnitude of the combined DTC did not differ significantly between pwMS and HC in any task. CONCLUSION: DTC is influenced by the complexity of the UL task, but was not significantly different between HC and cognitive intact, but mildly motor disabled pwMS.

Implicit and Explicit Learning of a Sequential Postural Weight-Shifting Task in Young and Older Adults.

Sequence-specific postural motor learning in a target-directed weight-shifting task in 12 older and 12 young participants was assessed. In the implicit sequence learning condition participants performed a concurrent spatial cognitive task and in the two explicit conditions participants were required to discover the sequence order either with or without the concurrent cognitive task. Participants moved a cursor on the screen from the center location to one of the target locations projected in a semi-circle and back by shifting their center of pressure (CoP) on force plates. During the training the targets appeared in a simple fixed 5-target sequence. Plan-based control (i.e., direction of the CoP displacement in the first part of the target-directed movement) improved by anticipating the sequence order in the implicit condition but not in the explicit dual task condition. Only the young participants were able to use the explicit knowledge of the sequence structure to improve the directional error as indicated by a significant decrease in directional error over practice and an increase in directional error with sequence removal in the explicit single task condition. Time spent in the second part of the movement trajectory to stabilize the cursor on the target location improved over training in both the implicit and explicit sequence learning conditions, for both age groups. These results might indicate that an implicit motor learning method, which holds back explicit awareness of task relevant features, may be desirable for improving plan-based motor control in older adults.