Effectiveness of a mobile application for independent computerized cognitive training in patients with mild cognitive impairment: study protocol for the NeNaE Study, a randomized controlled trial.

BACKGROUND: Mild cognitive impairment (MCI) involves cognitive decline beyond typical age-related changes, but without significant daily activity disruption. It can encompass various cognitive domains as the causes of MCI are diverse. MCI as well as frequent comorbid neuropsychiatric conditions like depression and anxiety affect individuals' quality of life. Early interventions are essential, and computerized cognitive training (cCT) is an established treatment method. This paper presents the protocol for the NeuroNation MED Effectiveness Study, evaluating the self-administered mobile cCT intervention ("NeuroNation MED") in individuals with MCI to assess training effects on cognitive domains, health competence, neuropsychiatric symptoms, psychological well-being, and the general application usability. METHODS: This study protocol presents a single-blinded multicenter randomized controlled trial that will be carried out in six study centers in Germany and Luxembourg. We included adults with MCI (existing F06.7 ICD-10-GM diagnosis and TICS ≥ 21 and ≤ 32). The intervention group will use a mobile, multi-domain cCT ("NeuroNation MED") for 12 weeks. Meanwhile, the wait list control group will receive standard medical care or no care. The eligibility of volunteers will be determined through a telephone screening. After completion of the baseline examination, patients will be randomly assigned to one of the experimental conditions in a 2:1 ratio. In total, 286 participants will be included in this study. The primary outcome is the change of cognitive performance measured by the index score of the screening module of the Neuropsychological Assessment Battery. Secondary outcomes are changes in the Cognitive Failures Questionnaire, Hospital Anxiety and Depression Scale, Health-49, Health Literacy Questionnaire, among others. All of the primary and secondary outcomes will be assessed at baseline and after the 12-week post-allocation period. Furthermore, the intervention group will undergo an assessment of the System Usability Scale, and the training data of the NeuroNation MED application will be analyzed. DISCUSSION: This study aims to assess the effectiveness of a mobile self-administered cCT in enhancing cognitive abilities among individuals diagnosed with MCI. Should the findings confirm the effectiveness of the NeuroNation MED app, it may confer possible benefits for the care management of patients with MCI, owing to the accessibility, cost-effectiveness, and home-based setting it provides. Specifically, the cCT program could provide patients with personalized cognitive training, educational resources, and relaxation techniques, enabling participants to independently engage in cognitive training sessions at home without further supervision. TRIAL REGISTRATION: German Clinical Trials Register DRKS00025133. Registered on November 5, 2021.

Neuropsychiatric symptoms and metamemory across the life span: psychometric properties of the German Multifactorial Memory Questionnaire (MMQ).

OBJECTIVE: We assessed the psychometric properties, established normative data for the German Multifactorial Memory Questionnaire (MMQ), and analyzed its association with neuropsychiatric factors across the life span to provide a validated metamemory assessment for a German-speaking population. METHODS: The three MMQ scales (memory satisfaction, self-rated ability, and strategy application) were translated into German, considering cultural, linguistic, and conceptual aspects. To validate the MMQ and assess associations with neuropsychiatric factors, the Complainer Profile Identification, Geriatric Depression Scale, Beck Anxiety Inventory, Pittsburgh Sleep Quality Index, and Short-Form-Health Survey were applied in an online study in 336 healthy participants with follow-up after 8 months. RESULTS: Psychometric evaluation of the German MMQ showed normal distribution of all scales and good to excellent validity, internal consistency, and retest reliability. We provide percentiles and normative data for z-score conversion. Importantly, even subclinically elevated scores in depressiveness and anxiety were associated with decreased memory satisfaction and self-rated ability. Furthermore, although the influence of age on the German MMQ scales was minimal, effects of neuropsychiatric factors such as sleep quality, anxiety, and depressiveness on MMQ Satisfaction and Ability varied across the life span. CONCLUSIONS: Our study provides a validated German translation of the MMQ with normative data and reliability measures, including reliable change scores. We show the impact of neuropsychiatric factors on the MMQ scales across the life span and emphasize the relevance of a multifactorial approach to metamemory as a measure of individualized everyday functionality and the importance of including neuropsychiatric factors into both research and clinical assessments of metamemory.

Translating spatial navigation evaluation from experimental to clinical settings: The virtual environments navigation assessment (VIENNA).

Spatial navigation abilities are frequently impaired in neurological disorders and they also decline with normal aging. Researchers and clinicians therefore need valid and easy-to-use spatial navigation assessment tools to study the impact of different neuropathologies and prevent relevant cognitive impairments from going undetected. However, current experimental paradigms rarely address which cognitive processes they recruit, often have resource-intensive setups, and usually require active navigation, e.g., using a joystick or keyboard, thus confounding cognitive performance with fine motor skills. Yet, for clinical feasibility, time-efficient paradigms are needed that are informative and easy to administer in participants with limited technical experience and diverging impairments. Here, we introduce the virtual environments navigation assessment (VIENNA), a virtual adaptation of a brief, standardized, and intuitive spatial navigation paradigm ( https://osf.io/kp4c5/ ). VIENNA is designed to assess spatial navigation without episodic memory demands, requires no interface device, and takes about 16 min to complete. We evaluated VIENNA in 79 healthy middle-aged to older participants (50-85 years) and provide evidence for its feasibility and construct validity. Tests of visuospatial and executive functions, but not episodic memory or selective attention, were identified as cognitive correlates of VIENNA, even when controlling for participant age and overall cognitive performance. Furthermore, VIENNA scores correlated with subjective navigation ability and age, but not with depressiveness, cognitive complaints, or education. The straightforward administration of VIENNA allows for its integration into routine neuropsychological assessments and enables differentiated evaluation of spatial navigation performance in patients with motor impairments and episodic memory deficits.

Structural brain changes in patients with post-COVID fatigue: a prospective observational study.

Background: Post-COVID syndrome is a severe long-term complication of COVID-19. Although fatigue and cognitive complaints are the most prominent symptoms, it is unclear whether they have structural correlates in the brain. We therefore explored the clinical characteristics of post-COVID fatigue, describe associated structural imaging changes, and determine what influences fatigue severity. Methods: We prospectively recruited 50 patients from neurological post-COVID outpatient clinics (age 18-69 years, 39f/8m) and matched non-COVID healthy controls between April 15 and December 31, 2021. Assessments included diffusion and volumetric MR imaging, neuropsychiatric, and cognitive testing. At 7.5 months (median, IQR 6.5-9.2) after the acute SARS-CoV-2 infection, moderate or severe fatigue was identified in 47/50 patients with post-COVID syndrome who were included in the analyses. As a clinical control group, we included 47 matched multiple sclerosis patients with fatigue. Findings: Our diffusion imaging analyses revealed aberrant fractional anisotropy of the thalamus. Diffusion markers correlated with fatigue severity, such as physical fatigue, fatigue-related impairment in everyday life (Bell score) and daytime sleepiness. Moreover, we observed shape deformations and decreased volumes of the left thalamus, putamen, and pallidum. These overlapped with the more extensive subcortical changes in MS and were associated with impaired short-term memory. While fatigue severity was not related to COVID-19 disease courses (6/47 hospitalised, 2/47 with ICU treatment), post-acute sleep quality and depressiveness emerged as associated factors and were accompanied by increased levels of anxiety and daytime sleepiness. Interpretation: Characteristic structural imaging changes of the thalamus and basal ganglia underlie the persistent fatigue experienced by patients with post-COVID syndrome. Evidence for pathological changes to these subcortical motor and cognitive hubs provides a key to the understanding of post-COVID fatigue and related neuropsychiatric complications. Funding: Deutsche Forschungsgemeinschaft (DFG) and German Ministry of Education and Research (BMBF).

Berlin Registry of Neuroimmunological entities (BERLimmun): protocol of a prospective observational study.

BACKGROUND: Large-scale disease overarching longitudinal data are rare in the field of neuroimmunology. However, such data could aid early disease stratification, understanding disease etiology and ultimately improve treatment decisions. The Berlin Registry of Neuroimmunological Entities (BERLimmun) is a longitudinal prospective observational study, which aims to identify diagnostic, disease activity and prognostic markers and to elucidate the underlying pathobiology of neuroimmunological diseases. METHODS: BERLimmun is a single-center prospective observational study of planned 650 patients with neuroimmunological disease entity (e.g. but not confined to: multiple sclerosis, isolated syndromes, neuromyelitis optica spectrum disorders) and 85 healthy participants with 15 years of follow-up. The protocol comprises annual in-person visits with multimodal standardized assessments of medical history, rater-based disability staging, patient-report of lifestyle, diet, general health and disease specific symptoms, tests of motor, cognitive and visual functions, structural imaging of the neuroaxis and retina and extensive sampling of biological specimen. DISCUSSION: The BERLimmun database allows to investigate multiple key aspects of neuroimmunological diseases, such as immunological differences between diagnoses or compared to healthy participants, interrelations between findings of functional impairment and structural change, trajectories of change for different biomarkers over time and, importantly, to study determinants of the long-term disease course. BERLimmun opens an opportunity to a better understanding and distinction of neuroimmunological diseases.

RGB-Depth Camera-Based Assessment of Motor Capacity: Normative Data for Six Standardized Motor Tasks.

BACKGROUND: Instrumental motion analysis constitutes a promising development in the assessment of motor function in clinical populations affected by movement disorders. To foster implementation and facilitate interpretation of respective outcomes, we aimed to establish normative data of healthy subjects for a markerless RGB-Depth camera-based motion analysis system and to illustrate their use. METHODS: We recorded 133 healthy adults (56% female) aged 20 to 60 years with an RGB-Depth camera-based motion analysis system. Forty-three spatiotemporal parameters were extracted from six short, standardized motor tasks-including three gait tasks, stepping in place, standing-up and sitting down, and a postural control task. Associations with confounding factors, height, weight, age, and sex were modelled using a predictive linear regression approach. A z-score normalization approach was provided to improve usability of the data. RESULTS: We reported descriptive statistics for each spatiotemporal parameter (mean, standard deviation, coefficient of variation, quartiles). Robust confounding associations emerged for step length and step width in comfortable speed gait only. Accessible normative data usage was lastly exemplified with recordings from one randomly selected individual with multiple sclerosis. CONCLUSION: We provided normative data for an RGB depth camera-based motion analysis system covering broad aspects of motor capacity.

Intuitive assessment of spatial navigation beyond episodic memory: Feasibility and proof of concept in middle-aged and elderly individuals.

Deficits in spatial navigation in three-dimensional space are prevalent in various neurological disorders and are a sensitive cognitive marker for prodromal Alzheimer's disease, but are also associated with non-pathological aging. However, standard neuropsychological tests used in clinical settings lack ecological validity to adequately assess spatial navigation. Experimental paradigms, on the other hand, are often too difficult for seniors or patients with cognitive or motor impairments since most require operating a human interface device (HID) or use complex episodic memory tasks. Here, we introduce an intuitive navigation assessment, which is conceptualized using cognitive models of spatial navigation and designed to account for the limited technical experience and diverging impairments of elderly participants and neurological patients. The brief computer paradigm uses videos of hallways filmed with eye tracking glasses, without employing an episodic memory task or requiring participants to operate a HID. Proof of concept data from 34 healthy, middle-aged and elderly participants (56-78 years) provide evidence for the assessment's feasibility and construct validity as a navigation paradigm. Test performance showed normal distribution and was sensitive to age and education, which needs to be considered when investigating the assessment's psychometric properties in larger samples and clinical populations. Correlations of the navigation assessment with other neuropsychological tests confirmed its dependence on visuospatial skills rather than visual episodic memory, with age driving the association with working memory. The novel paradigm is suitable for a differentiated investigation of spatial navigation in elderly individuals and promising for experimental research in clinical settings.

Multidimensional Evaluation of Virtual Reality Paradigms in Clinical Neuropsychology: Application of the VR-Check Framework.

Virtual reality (VR) represents a key technology of the 21st century, attracting substantial interest from a wide range of scientific disciplines. With regard to clinical neuropsychology, a multitude of new VR applications are being developed to overcome the limitations of classical paradigms. Consequently, researchers increasingly face the challenge of systematically evaluating the characteristics and quality of VR applications to design the optimal paradigm for their specific research question and study population. However, the multifaceted character of contemporary VR is not adequately captured by the traditional quality criteria (ie, objectivity, reliability, validity), highlighting the need for an extended paradigm evaluation framework. To address this gap, we propose a multidimensional evaluation framework for VR applications in clinical neuropsychology, summarized as an easy-to-use checklist (VR-Check). This framework rests on 10 main evaluation dimensions encompassing cognitive domain specificity, ecological relevance, technical feasibility, user feasibility, user motivation, task adaptability, performance quantification, immersive capacities, training feasibility, and predictable pitfalls. We show how VR-Check enables systematic and comparative paradigm optimization by illustrating its application in an exemplary research project on the assessment of spatial cognition and executive functions with immersive VR. This application furthermore demonstrates how the framework allows researchers to identify across-domain trade-offs, makes deliberate design decisions explicit, and optimizes the allocation of study resources. Complementing recent approaches to standardize clinical VR studies, the VR-Check framework enables systematic and project-specific paradigm optimization for behavioral and cognitive research in neuropsychology.