Evaluation of walking activity and gait to identify physical and mental fatigue in neurodegenerative and immune disorders: preliminary insights from the IDEA-FAST feasibility study.

BACKGROUND: Many individuals with neurodegenerative (NDD) and immune-mediated inflammatory disorders (IMID) experience debilitating fatigue. Currently, assessments of fatigue rely on patient reported outcomes (PROs), which are subjective and prone to recall biases. Wearable devices, however, provide objective and reliable estimates of gait, an essential component of health, and may present objective evidence of fatigue. This study explored the relationships between gait characteristics derived from an inertial measurement unit (IMU) and patient-reported fatigue in the IDEA-FAST feasibility study. METHODS: Participants with IMIDs and NDDs (Parkinson's disease (PD), Huntington's disease (HD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjogren's syndrome (PSS), and inflammatory bowel disease (IBD)) wore a lower-back IMU continuously for up to 10 days at home. Concurrently, participants completed PROs (physical fatigue (PF) and mental fatigue (MF)) up to four times a day. Macro (volume, variability, pattern, and acceleration vector magnitude) and micro (pace, rhythm, variability, asymmetry, and postural control) gait characteristics were extracted from the accelerometer data. The associations of these measures with the PROs were evaluated using a generalised linear mixed-effects model (GLMM) and binary classification with machine learning. RESULTS: Data were recorded from 72 participants: PD = 13, HD = 9, RA = 12, SLE = 9, PSS = 14, IBD = 15. For the GLMM, the variability of the non-walking bouts length (in seconds) with PF returned the highest conditional R2, 0.165, and with MF the highest marginal R2, 0.0018. For the machine learning classifiers, the highest accuracy of the current analysis was returned by the micro gait characteristics with an intrasubject cross validation method and MF as 56.90% (precision = 43.9%, recall = 51.4%). Overall, the acceleration vector magnitude, bout length variation, postural control, and gait rhythm were the most interesting characteristics for future analysis. CONCLUSIONS: Counterintuitively, the outcomes indicate that there is a weak relationship between typical gait measures and abnormal fatigue. However, factors such as the COVID-19 pandemic may have impacted gait behaviours. Therefore, further investigations with a larger cohort are required to fully understand the relationship between gait and abnormal fatigue.

Which Comprehensive Geriatric Assessment (CGA) instruments are currently used in Germany: a survey.

BACKGROUND: The Comprehensive Geriatric Assessment (CGA) records geriatric syndromes in a standardized manner, allowing individualized treatment tailored to the patient's needs and resources. Its use has shown a beneficial effect on the functional outcome and survival of geriatric patients. A recently published German S1 guideline for level 2 CGA provides recommendations for the use of a broad variety of different assessment instruments for each geriatric syndrome. However, the actual use of assessment instruments in routine geriatric clinical practice and its consistency with the guideline and the current state of literature has not been investigated to date. METHODS: An online survey was developed by an expert group of geriatricians and sent to all licenced geriatricians (n = 569) within Germany. The survey included the following geriatric syndromes: motor function and self-help capability, cognition, depression, pain, dysphagia and nutrition, social status and comorbidity, pressure ulcers, language and speech, delirium, and frailty. Respondents were asked to report which geriatric assessment instruments are used to assess the respective syndromes. RESULTS: A total of 122 clinicians participated in the survey (response rate: 21%); after data cleaning, 76 data sets remained for analysis. All participants regularly used assessment instruments in the following categories: motor function, self-help capability, cognition, depression, and pain. The most frequently used instruments in these categories were the Timed Up and Go (TUG), the Barthel Index (BI), the Mini Mental State Examination (MMSE), the Geriatric Depression Scale (GDS), and the Visual Analogue Scale (VAS). Limited or heterogenous assessments are used in the following categories: delirium, frailty and social status. CONCLUSIONS: Our results show that the assessment of motor function, self-help capability, cognition, depression, pain, and dysphagia and nutrition is consistent with the recommendations of the S1 guideline for level 2 CGA. Instruments recommended for more frequent use include the Short Physical Performance Battery (SPPB), the Montreal Cognitive Assessment (MoCA), and the WHO-5 (depression). There is a particular need for standardized assessment of delirium, frailty and social status. The harmonization of assessment instruments throughout geriatric departments shall enable more effective treatment and prevention of age-related diseases and syndromes.

Fatigue-Related Changes of Daily Function: Most Promising Measures for the Digital Age.

Background: Fatigue is a prominent symptom in many diseases and is strongly associated with impaired daily function. The measurement of daily function is currently almost always done with questionnaires, which are subjective and imprecise. With the recent advances of digital wearable technologies, novel approaches to evaluate daily function quantitatively and objectively in real-life conditions are increasingly possible. This also creates new possibilities to measure fatigue-related changes of daily function using such technologies. Summary: This review examines which digitally assessable parameters in immune-mediated inflammatory and neurodegenerative diseases may have the greatest potential to reflect fatigue-related changes of daily function. Key Messages: Results of a standardized analysis of the literature reporting about perception-, capacity-, and performance-evaluating assessment tools indicate that changes of the following parameters: physical activity, independence of daily living, social participation, working life, mental status, cognitive and aerobic capacity, and supervised and unsupervised mobility performance have the highest potential to reflect fatigue-related changes of daily function. These parameters thus hold the greatest potential for quantitatively measuring fatigue in representative diseases in real-life conditions, e.g., with digital wearable technologies. Furthermore, to the best of our knowledge, this is a new approach to analysing evidence for the design of performance-based digital assessment protocols in human research, which may stimulate further systematic research in this area.

Identification of Fatigue and Sleepiness in Immune and Neurodegenerative Disorders from Measures of Real-World Gait Variability.

Current assessments of fatigue and sleepiness rely on patient reported outcomes (PROs), which are subjective and prone to recall bias. The current study investigated the use of gait variability in the "real world" to identify patient fatigue and daytime sleepiness. Inertial measurement units were worn on the lower backs of 159 participants (117 with six different immune and neurodegenerative disorders and 42 healthy controls) for up to 20 days, whom completed regular PROs. To address walking bouts that were short and sparse, four feature groups were considered: sequence-independent variability (SIV), sequence-dependant variability (SDV), padded SDV (PSDV), and typical gait variability (TGV) measures. These gait variability measures were extracted from step, stride, stance, and swing time, step length, and step velocity. These different approaches were compared using correlations and four machine learning classifiers to separate low/high fatigue and sleepiness.Most balanced accuracies were above 50%, the highest was 57.04% from TGV measures. The strongest correlation was 0.262 from an SDV feature against sleepiness. Overall, TGV measures had lower correlations and classification accuracies.Identifying fatigue or sleepiness from gait variability is extremely complex and requires more investigation with a larger data set, but these measures have shown performances that could contribute to a larger feature set.Clinical relevance- Gait variability has been repeatedly used to assess fatigue in the lab. The current study, however, explores gait variability for fatigue and daytime sleepiness in real-world scenarios with multiple gait-impacted disorders.

Assessing fatigue and sleep in chronic diseases using physiological signals from wearables: A pilot study.

Problems with fatigue and sleep are highly prevalent in patients with chronic diseases and often rated among the most disabling symptoms, impairing their activities of daily living and the health-related quality of life (HRQoL). Currently, they are evaluated primarily via Patient Reported Outcomes (PROs), which can suffer from recall biases and have limited sensitivity to temporal variations. Objective measurements from wearable sensors allow to reliably quantify disease state, changes in the HRQoL, and evaluate therapeutic outcomes. This work investigates the feasibility of capturing continuous physiological signals from an electrocardiography-based wearable device for remote monitoring of fatigue and sleep and quantifies the relationship of objective digital measures to self-reported fatigue and sleep disturbances. 136 individuals were followed for a total of 1,297 recording days in a longitudinal multi-site study conducted in free-living settings and registered with the German Clinical Trial Registry (DRKS00021693). Participants comprised healthy individuals (N = 39) and patients with neurodegenerative disorders (NDD, N = 31) and immune mediated inflammatory diseases (IMID, N = 66). Objective physiological measures correlated with fatigue and sleep PROs, while demonstrating reasonable signal quality. Furthermore, analysis of heart rate recovery estimated during activities of daily living showed significant differences between healthy and patient groups. This work underscores the promise and sensitivity of novel digital measures from multimodal sensor time-series to differentiate chronic patients from healthy individuals and monitor their HRQoL. The presented work provides clinicians with realistic insights of continuous at home patient monitoring and its practical value in quantitative assessment of fatigue and sleep, an area of unmet need.

Association between heart failure severity and mobility in geriatric patients: an in-clinic study with wearable sensors.

BACKGROUND: Individuals with heart failure (HF) frequently experience limitations in mobility, but specific aspects of these limitations are not well understood. This study investigated the association of HF severity, based on the New York Heart Association (NYHA) classes, with digital mobility outcomes (DMOs) and handgrip strength in older inpatients with HF. METHODS: For this explorative analysis, hospital admission and discharge data from an ongoing, prospective cohort study were used. The sample included older participants with HF and a sub-sample of heart-healthy individuals. Participants were equipped with a wearable inertial measurement unit (IMU) system during mobility performance (balancing, sit-to-stand transfer, walking). We analyzed the association between 17 DMOs and HF severity with multiple linear regression models. RESULTS: The total sample included 61 older participants (65-97 years of age, 55.7% female). Of all DMOs, only sway path in a semi-tandem stance position (m/s²) showed a relevant association with NYHA classes (admission: ß = -0.28, P = 0.09; discharge: ß = -0.39, P = 0.02). Handgrip strength showed a trend towards a significant association (admission: ß = -0.15, P = 0.10; discharge: ß = -0.15, P = 0.19). CONCLUSIONS: This is to our best knowledge the first analysis on the association of HF severity and IMU-based DMOs. Sway path and handgrip strength may be the most promising parameters for monitoring mobility aspects in treatment of HF.

Fatigue and cognitive impairment after COVID-19: A prospective multicentre study.

Background: Reliable estimates of frequency, severity and associated factors of both fatigue and cognitive impairment after COVID-19 are needed. Also, it is not clear whether the two are distinct sequelae of COVID-19 or part of the same syndrome." Methods: In this prospective multicentre study, frequency of post-COVID fatigue and cognitive impairment were assessed in n = 969 patients (535 [55%] female) ≥6 months after SARS-CoV-2 infection with the FACIT-Fatigue scale (cut-off ≤30) and Montreal Cognitive Assessment (≤25 mild, ≤17 moderate impairment) between November 15, 2020 and September 29, 2021 at University Medical Center Schleswig-Holstein, Campus Kiel and University Hospital Würzburg in Germany. 969 matched non-COVID controls were drawn from a pre-pandemic, randomised, Germany-wide population survey which also included the FACIT-Fatigue scale. Associated sociodemographic, comorbid, clinical, psychosocial factors and laboratory markers were identified with univariate and multivariable linear regression models. Findings: On average 9 months after infection, 19% of patients had clinically relevant fatigue, compared to 8% of matched non-COVID controls (p < 0.001). Factors associated with fatigue were female gender, younger age, history of depression and the number of acute COVID symptoms. Among acute COVID symptoms, altered consciousness, dizziness and myalgia were most strongly associated with long-term fatigue. Moreover, 26% of patients had mild and 1% had moderate cognitive impairment. Factors associated with cognitive impairment were older age, male gender, shorter education and a history of neuropsychiatric disease. There was no significant correlation between fatigue and cognitive impairment and only 5% of patients suffered from both conditions. Interpretation: Fatigue and cognitive impairment are two common, but distinct sequelae of COVID-19 with potentially separate pathophysiological pathways. Funding: German Federal Ministry of Education and Research (BMBF).

Does Executive Function Influence Walking in Acutely Hospitalized Patients With Advanced Parkinson's Disease: A Quantitative Analysis.

Introduction: It is well-known that, in Parkinson's disease (PD), executive function (EF) and motor deficits lead to reduced walking performance. As previous studies investigated mainly patients during the compensated phases of the disease, the aim of this study was to investigate the above associations in acutely hospitalized patients with PD. Methods: A total of seventy-four acutely hospitalized patients with PD were assessed with the delta Trail Making Test (ΔTMT, TMT-B minus TMT-A) and the Movement Disorder Society-revised version of the motor part of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS III). Walking performance was assessed with wearable sensors under single (ST; fast and normal pace) and dual-task (DT; walking and checking boxes as the motor secondary task and walking and subtracting seven consecutively from a given three-digit number as the cognitive secondary task) conditions over 20 m. Multiple linear regression and Bayes factor BF10 were performed for each walking parameter and their dual-task costs while walking (DTC) as dependent variables and also included ΔTMT, MDS-UPDRS III, age, and gender. Results: Under ST, significant negative effects of the use of a walking aid and MDS-UPDRS III on gait speed and at a fast pace on the number of steps were observed. Moreover, depending on the pace, the use of a walking aid, age, and gender affected step time variability. Under walking-cognitive DT, a resolved variance of 23% was observed in the overall model for step time variability DTC, driven mainly by age (ß = 0.26, p = 0.09). Under DT, no other significant effects could be observed. ΔTMT showed no significant associations with any of the walking conditions. Discussion: The results of this study suggest that, in acutely hospitalized patients with PD, reduced walking performance is mainly explained by the use of a walking aid, motor symptoms, age, and gender, and EF deficits surprisingly do not seem to play a significant role. However, these patients with PD should avoid walking-cognitive DT situations, as under this condition, especially step time variability, a parameter associated with the risk of falling in PD worsens.

What contributes most to the SPPB and its subscores in hospitalized geriatric patients: an ICF model-based approach.

BACKGROUND: Mobility deficits are highly prevalent among geriatric patients and have serious impact on quality of life, hospitalizations, and mortality. This study aims to capture predictors of mobility deficits in hospitalized geriatric patients using the International Classification of Functioning, Disability and Health (ICF) model as a framework. METHODS: Data were obtained from n = 397 patients (78 ± 7 years, 15 ± 7 ICD-11 diagnoses) on a geriatric ward at time of admission. Mobility was assessed using the Short Physical Performance Battery (SPPB) total score and gait, static balance and transfer subscores. Parameters from an extensive assessment including medical history, neuropsychological and motor examination, and questionnaires were assigned to the five components of the ICF model. Spearman's Correlation and multiple linear regression analyses were calculated to identify predictors for the SPPB total score and subscores. RESULTS: Use of walking aid, fear of falling (FOF, but not occurrence of previous falls), participation in society, ADL and grip strength were strongly associated with the SPPB total score and all subscores (p < .001). FOF and grip strength were significant predictors for the SPPB total score as well as for gait and transfer subscores. FOF also showed a strong association with the static balance subscore. The clinical parameters of the ICF model could only partially explain the variance in the SPPB total score (24%) and subscores (12-23%), with no parameter from the activities and participation component being significantly predictive. CONCLUSIONS: FOF and reduced grip strength are associated with mobility deficits in a hospitalized geriatric cohort. Further research should focus on interventions to reduce FOF and increase muscle strength in geriatric patients. Moreover, there is a need for ICF-based assessments instruments (especially in the activities and participation components) that allow a holistic view on mobility and further daily life-relevant health aspects in geriatric patients.

Static Balance and Chair-Rise Performance in Neurogeriatric Patients: Promising Short Physical Performance Battery-Derived Predictors of Fear of Falling.

Background: Fear of falling (FOF) negatively affects health-related quality of life and is common in neurogeriatric patients, however, related parameters are not well understood. This study investigated the relationship between FOF, physical performance (as assessed with the Short Physical Performance Battery and its subscores) and other aspects of sarcopenia in a sample of hospitalized neurogeriatric patients. Methods: In 124 neurogeriatric patients, FOF was assessed with the Falls Efficacy Scale International (FES-I). Physical performance was measured using the Short Physical Performance Battery (SPPB) including walking duration, balance and five times sit-to-stand task (5xSST) subscores. Appendicular skeletal muscle mass (ASMM) was estimated with the cross-validated Sergi equation using Bioelectrical impedance analysis measures. The Depression im Alter-Skala (DIA-S) was used to assess depressive symptoms. Multiple regression models with FES-I score as outcome variable were computed using backward selection with AICc as selection criterion, including: (i) SPPB total score, ASMM/height2, grip strength, age, gender, positive fall history, number of medications, use of a walking aid, DIA-S score and Montreal Cognitive Assessment (MoCA) score; and (ii) SPPB subscores, ASMM/height2, grip strength, age, gender, positive fall history, number of medications, DIA-S score and MoCA score, once with and once without including use of a walking aid as independent variable. Results: Lower SPPB total score, as well as lower SPPB balance and 5xSST subscores were associated with higher FES-I scores, but SPPB walking duration subscore was not. Moreover, DIA-S, number of medications and use of a walking aid were significantly associated with FOF. Conclusion: Our preliminary results suggest that -if confirmed by subsequent studies- it may be worthwhile to screen patients with low SPPB balance and 5xSST subscores for FOF, and to treat especially these mobility deficits in neurogeriatric patients with FOF. Moreover, training neurogeriatric patients to use their walking aids correctly, critical evaluation of medication and treating depressive symptoms may further help reduce FOF in this highly vulnerable cohort.

Cognitive parameters can predict change of walking performance in advanced Parkinson's disease - Chances and limits of early rehabilitation.

Introduction: Links between cognition and walking performance in patients with Parkinson's disease (PD), which both decline with disease progression, are well known. There is lack of knowledge regarding the predictive value of cognition for changes in walking performance after individualized therapy. The aim of this study is to identify relevant predictive cognitive and affective parameters, measurable in daily clinical routines, for change in quantitative walking performance after early geriatric rehabilitation. Methods: Forty-seven acutely hospitalized patients with advanced PD were assessed at baseline (T1) and at the end (T2) of a 2-week early rehabilitative geriatric complex treatment (ERGCT). Global cognitive performance (Montreal Cognitive Assessment, MoCA), EF and divided attention (Trail Making Test B minus A, delta TMT), depressive symptoms, and fear of falling were assessed at T1. Change in walking performance was determined by the difference in quantitative walking parameters extracted from a sensor-based movement analysis over 20 m straight walking in single (ST, fast and normal pace) and dual task (DT, with secondary cognitive, respectively, motor task) conditions between T1 and T2. Bayesian regression (using Bayes Factor BF10) and multiple linear regression models were used to determine the association of non-motor characteristics for change in walking performance. Results: Under ST, there was moderate evidence (BF10 = 7.8, respectively, BF10 = 4.4) that lower performance in the ∆TMT at baseline is associated with lower reduction of step time asymmetry after treatment (R 2 adj = 0.26, p ≤ 0.008, respectively, R 2 adj = 0.18, p ≤ 0.009). Under DT walking-cognitive, there was strong evidence (BF10 = 29.9, respectively, BF10 = 27.9) that lower performance in the ∆TMT is associated with more reduced stride time and double limb support (R 2 adj = 0.62, p ≤ 0.002, respectively, R 2 adj = 0.51, p ≤ 0.009). There was moderate evidence (BF10 = 5.1) that a higher MoCA total score was associated with increased gait speed after treatment (R 2 adj = 0.30, p ≤ 0.02). Discussion: Our results indicate that the effect of ERGT on change in walking performance is limited for patients with deficits in EF and divided attention. However, these patients also seem to walk more cautiously after treatment in walking situations with additional cognitive demand. Therefore, future development of individualized treatment algorithms is required, which address individual needs of these vulnerable patients.

Motor, cognitive and mobility deficits in 1000 geriatric patients: protocol of a quantitative observational study before and after routine clinical geriatric treatment - the ComOn-study.

BACKGROUND: Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative markers with clinical relevance for motor and cognitive deficits, (ii) to investigate the interaction between both motor and cognitive deficits and (iii) to assess health status as well as treatment outcome of 1000 geriatric inpatients in hospitals of Kiel (Germany), Brescia (Italy), Porto (Portugal), Curitiba (Brazil) and Bochum (Germany). METHODS: This is a prospective, explorative observational multi-center study. In addition to the comprehensive geriatric assessment, quantitative measures of reduced mobility and motor and cognitive deficits are performed before and after a two week's inpatient stay. Components of the assessment are mobile technology-based assessments of gait, balance and transfer performance, neuropsychological tests, frailty, sarcopenia, autonomic dysfunction and sensation, and questionnaires to assess behavioral deficits, activities of daily living, quality of life, fear of falling and dysphagia. Structural MRI and an unsupervised 24/7 home assessment of mobility are performed in a subgroup of participants. The study will also investigate the minimal clinically relevant change of the investigated parameters. DISCUSSION: This study will help form a better understanding of symptoms and their complex interactions and treatment effects in a large geriatric cohort.