An overview of screening instruments for cognition and behavior in patients with ALS: selecting the appropriate tool for clinical practice.

Objective: Patients with amyotrophic lateral sclerosis (ALS) not only show motor deficits, but may also have cognitive and/or behavioral impairments. Recognizing these impairments is crucial as they are associated with lower quality of life, shorter survival, and increased caregiver burden. Therefore, ALS-specific neuropsychological screening instruments have been developed that can account for motor and speech difficulties. This study provides an overview and comparison of these screeners. Methods: A systematic review was conducted using Medline and Embase. Articles describing cognitive/behavioral screening instruments assessed in ALS patients were included. Screening instruments were compared on multiple factors, such as domains, adaptability, required time, and validation. Results: We included 99 articles, reporting on nine cognitive screeners (i.e. ACE-R, ALS-BCA, ALS-CBS, ECAS, FAB, MMSE, MoCA, PSSFTS, and UCSF-SB), of which five ALS-specific. Furthermore, eight behavioral screeners (i.e. ALS-FTD-Q, AES, BBI, DAS, FBI, FrSBe, MiND-B, and NPI) were reported on, of which three ALS-specific. Conclusion: Considering the broad range of cognitive domains, adaptability, and satisfying validity, the ALS-CBS and ECAS appear to be the most suitable screeners to detect cognitive and behavioral changes in ALS. The BBI appears to be the best option to screen for behavioral changes in ALS, since all relevant domains are assessed, motor-related problems are considered, and has a satisfactory validity. The MiND-B and ALS-FTD-Q are promising as well. In general, all screening instruments would benefit from additional validation research to gain greater insights into test characteristics and to aid clinicians in selecting screening tools for use in clinical practice

Feasibility and user-experience of virtual reality in neuropsychological assessment following stroke

Virtual Reality (VR) offers the possibility to assess cognitive functioning in a dynamic environment resembling daily life. In this cross-sectional study, we used two user interfaces, namely non-immersive VR by using a computer monitor (CM) and immersive VR by using a head-mounted display (HMD). We investigated (1) potential differences in feasibility, user-experience, and a potential preference for one user interface over another between stroke patients and healthy controls; (2) potential differences in feasibility, user-experience, and preference between patients referred for inpatient rehabilitation care and patients referred for outpatient rehabilitation care; and (3) potential demographic and clinical characteristics that were related to patients' preference for one user interface over another. Stroke patients (n = 88) and healthy controls (n = 66) performed a VR-task with a CM and HMD. Both user interfaces were feasible to use, irrespective of clinical referral (in- or outpatient rehabilitation care). Patients reported an enhanced feeling of engagement, transportation, flow, and presence, but more negative side effects when tested with a HMD, compared to a CM. The majority of stroke patients had no preference for one user interface over the other, yet younger patients tended to prefer a HMD. VR seems highly feasible in stroke patients

Applying machine learning to dissociate between stroke patients and healthy controls using eye movement features obtained from a virtual reality task

Conventional neuropsychological tests do not represent the complex and dynamic situations encountered in daily life. Immersive virtual reality simulations can be used to simulate dynamic and interactive situations in a controlled setting. Adding eye tracking to such simulations may provide highly detailed outcome measures, and has great potential for neuropsychological assessment. Here, participants (83 stroke patients and 103 healthy controls) we instructed to find either 3 or 7 items from a shopping list in a virtual super market environment while eye movements were being recorded. Using Logistic Regression and Support Vector Machine models, we aimed to predict the task of the participant and whether they belonged to the stroke or the control group. With a limited number of eye movement features, our models achieved an average Area Under the Curve (AUC) of .76 in predicting whether each participant was assigned a short or long shopping list (3 or 7 items). Identifying participant as either stroke patients and controls led to an AUC of .64. In both classification tasks, the frequency with which aisles were revisited was the most dissociating feature. As such, eye movement data obtained from a virtual reality simulation contain a rich set of signatures for detecting cognitive deficits, opening the door to potential clinical applications

Longitudinal Effects of Asymptomatic C9orf72 Carriership on Brain Morphology

Objective: We investigated effects of C9orf72 repeat expansion and gene expression on longitudinal cerebral changes before symptom onset. Methods: We enrolled 79 asymptomatic family members (AFMs) from 9 families with C9orf72 repeat expansion. Twenty-eight AFMs carried the mutation (C9+). Participants had up to 3 magnetic resonance imaging (MRI) scans, after which we compared motor cortex and motor tracts between C9+ and C9− AFMs using mixed effects models, incorporating kinship to correct for familial relations and lessen effects of other genetic factors. We also compared cortical, subcortical, cerebellar, and connectome structural measurements in a hypothesis-free analysis. We correlated regional C9orf72 expression in donor brains with the pattern of cortical thinning in C9+ AFMs using meta-regression. For comparison, we included 42 C9+ and 439 C9− patients with amyotrophic lateral sclerosis (ALS) in this analysis. Results: C9+ AFM motor cortex had less gyrification and was thinner than in C9− AFMs, without differences in motor tracts. Whole brain analysis revealed thinner cortex and less gyrification in parietal, occipital, and temporal regions, smaller thalami and right hippocampus, and affected frontotemporal connections. Thinning of bilateral precentral, precuneus, and left superior parietal cortex was faster in C9+ than in C9− AFMs. Higher C9orf72 expression correlated with thinner cortex in both C9+ AFMs and C9+ ALS patients. Interpretation: In asymptomatic C9orf72 repeat expansion carriers, brain MRI reveals widespread features suggestive of impaired neurodevelopment, along with faster decline of motor and parietal cortex than found in normal aging. C9orf72 expression might play a role in cortical development, and consequently explain the specific brain abnormalities of mutation carriers. ANN NEUROL 2023;93:668–680

Digital neuropsychological assessment: Feasibility and applicability in patients with acquired brain injury

INTRODUCTION: Digital neuropsychological assessment (d-NPA) has several advantages over paper-and-pencil tests in neuropsychological assessment, such as a more standardized stimulus presentation and response acquisition. We investigated (1) the feasibility and user-experience of a d-NPA in patients with acquired brain injury (ABI) and healthy controls; (2) the applicability of conventional paper-and-pencil norms on digital tests; and (3) whether familiarity with a tablet would affect test performance on a tablet. METHOD: We administered a d-NPA in stroke patients (n = 59), traumatic brain injury patients (n = 61) and healthy controls (n = 159). The neuropsychological tests were presented on a tablet and participants used a pencil stylus to respond. We examined the completion rate to assess the feasibility, and a semi-structured interview was conducted to examine the user-experience. The applicability of conventional norms was examined by the number of healthy controls performing <10th percentile, which was expected to be no more than 10%. The effect of tablet familiarity on test performance was examined with a regression-based model. RESULTS: Overall, 94% of patients completed the d-NPA. The d-NPA was considered pleasant by patients and healthy controls. Conventional norms that exist for paper-and-pencil tests were not applicable on the digital version of the tests, as up to 34% of healthy controls showed an abnormal performance on half of the tests. Tablet familiarity did not affect test performance on a tablet, indicating that participants who were more experienced with working with a tablet did not perform better on digital tests. CONCLUSIONS: The administration of a d-NPA is feasible in patients with ABI. Familiarity with a tablet did not impact test performance, which is particularly important in neuropsychological assessment. Future research should focus on developing norms in order to implement a d-NPA in clinical practice

CoCo - participation: The development and clinical use of a novel inventory measuring cognitive complaints in daily life

Cognitive difficulties can be subtle and only come to light when patients return home from inpatient care and start to participate in society. Subjective cognitive complaints often interfere with participation, hence capturing cognitive complaints systematically is important. We developed a patient- and relative-reported measure to assess cognitive complaints during daily life activities across the memory, attention and executive domain for patients with acquired brain injury (ABI). The inventory Cognitive Complaints - Participation (CoCo-P) was created based on a literature review, consultations with experts, semi-structured interviews with patients, and a quantitative study. The inventory was administered to patients with ABI (n = 46), their relatives (n = 33) and healthy controls (n = 102) to finalize the inventory. We examined the reported complaints per daily life activity and cognitive domain of patients and healthy controls, and we compared the patients’ and relatives’ reports. The majority of patients (87–96%) experienced cognitive complaints, mostly related to attention, at work/education, during leisure activities, and in contact with family/friends and community. Patients reported more cognitive complaints than relatives. The CoCo-P seems appropriate to capture cognitive complaints in daily life in patients with mild ABI. Additional research is needed in terms of reliability and validity

The journey is just as important as the destination—Digital neuropsychological assessment provides performance stability measures in patients with acquired brain injury

Background Cognitive performances on neuropsychological paper-and-pencil tests are generally evaluated quantitatively by examining a final score (e.g., total duration). Digital tests allow for a quantitative evaluation of “how” a patient attained a final score, which opens the possibility to assess more subtle cognitive impairment even when final scores are evaluated as normal. We assessed performance stability (i.e., the number of fluctuations in test performance) to investigate (1) differences in performance stability between patients with acquired brain injury (ABI) and healthy controls; (2) the added value of performance stability measures in patients with ABI; and (3) the relation between performance stability and cognitive complaints in daily life in patients with ABI. Methods We administered three digital neuropsychological tests (Rey Auditory Verbal Learning Test, Trail Making Test, Stroop Colour and Word Test) and the Cognitive Complaints—Participation (CoCo-P) inventory in patients with ABI (n = 161) and healthy controls (n = 91). Results Patients with ABI fluctuated more in their performance on all tests, when compared to healthy controls. Furthermore, 4–15% of patients who performed inside normal range on the conventional final scores were outside normal range on the performance stability measures. The performance stability measures, nor the conventional final scores, were associated with cognitive complaints in daily life

The journey is just as important as the destination—Digital neuropsychological assessment provides performance stability measures in patients with acquired brain injury

Background Cognitive performances on neuropsychological paper-and-pencil tests are generally evaluated quantitatively by examining a final score (e.g., total duration). Digital tests allow for a quantitative evaluation of “how” a patient attained a final score, which opens the possibility to assess more subtle cognitive impairment even when final scores are evaluated as normal. We assessed performance stability (i.e., the number of fluctuations in test performance) to investigate (1) differences in performance stability between patients with acquired brain injury (ABI) and healthy controls; (2) the added value of performance stability measures in patients with ABI; and (3) the relation between performance stability and cognitive complaints in daily life in patients with ABI. Methods We administered three digital neuropsychological tests (Rey Auditory Verbal Learning Test, Trail Making Test, Stroop Colour and Word Test) and the Cognitive Complaints—Participation (CoCo-P) inventory in patients with ABI (n = 161) and healthy controls (n = 91). Results Patients with ABI fluctuated more in their performance on all tests, when compared to healthy controls. Furthermore, 4–15% of patients who performed inside normal range on the conventional final scores were outside normal range on the performance stability measures. The performance stability measures, nor the conventional final scores, were associated with cognitive complaints in daily life

CoCo - participation: The development and clinical use of a novel inventory measuring cognitive complaints in daily life

Cognitive difficulties can be subtle and only come to light when patients return home from inpatient care and start to participate in society. Subjective cognitive complaints often interfere with participation, hence capturing cognitive complaints systematically is important. We developed a patient- and relative-reported measure to assess cognitive complaints during daily life activities across the memory, attention and executive domain for patients with acquired brain injury (ABI). The inventory Cognitive Complaints - Participation (CoCo-P) was created based on a literature review, consultations with experts, semi-structured interviews with patients, and a quantitative study. The inventory was administered to patients with ABI (n = 46), their relatives (n = 33) and healthy controls (n = 102) to finalize the inventory. We examined the reported complaints per daily life activity and cognitive domain of patients and healthy controls, and we compared the patients’ and relatives’ reports. The majority of patients (87–96%) experienced cognitive complaints, mostly related to attention, at work/education, during leisure activities, and in contact with family/friends and community. Patients reported more cognitive complaints than relatives. The CoCo-P seems appropriate to capture cognitive complaints in daily life in patients with mild ABI. Additional research is needed in terms of reliability and validity

Digital neuropsychological assessment: Feasibility and applicability in patients with acquired brain injury

INTRODUCTION: Digital neuropsychological assessment (d-NPA) has several advantages over paper-and-pencil tests in neuropsychological assessment, such as a more standardized stimulus presentation and response acquisition. We investigated (1) the feasibility and user-experience of a d-NPA in patients with acquired brain injury (ABI) and healthy controls; (2) the applicability of conventional paper-and-pencil norms on digital tests; and (3) whether familiarity with a tablet would affect test performance on a tablet. METHOD: We administered a d-NPA in stroke patients (n = 59), traumatic brain injury patients (n = 61) and healthy controls (n = 159). The neuropsychological tests were presented on a tablet and participants used a pencil stylus to respond. We examined the completion rate to assess the feasibility, and a semi-structured interview was conducted to examine the user-experience. The applicability of conventional norms was examined by the number of healthy controls performing <10th percentile, which was expected to be no more than 10%. The effect of tablet familiarity on test performance was examined with a regression-based model. RESULTS: Overall, 94% of patients completed the d-NPA. The d-NPA was considered pleasant by patients and healthy controls. Conventional norms that exist for paper-and-pencil tests were not applicable on the digital version of the tests, as up to 34% of healthy controls showed an abnormal performance on half of the tests. Tablet familiarity did not affect test performance on a tablet, indicating that participants who were more experienced with working with a tablet did not perform better on digital tests. CONCLUSIONS: The administration of a d-NPA is feasible in patients with ABI. Familiarity with a tablet did not impact test performance, which is particularly important in neuropsychological assessment. Future research should focus on developing norms in order to implement a d-NPA in clinical practice