The immersive virtual memory task: Assessing object-location memory in neurological patients using immersive virtual reality.

TRIAL REGISTRATION: German Clinical Trials Register identifier: DRKS00024005.

The effect of high vs. low intensity neuropsychological treatment on working memory in patients with acquired brain injury.

AIM: To evaluate the combined effect of compensation therapy and functional training on working memory (WM) in patients with acquired injury and chronic cognitive deficits by investigating the dose-response relationship and specificity of transfer effects. RESEARCH DESIGN: Double-blind randomized controlled trial. METHODS: All patients underwent 4 weeks of compensation therapy in a day-care setting. In addition, they received either 20 sessions of computer-based WM training (n = 11) or attention training (n = 9). Transfer effects on cognition and their functional relevance in daily life were assessed before treatment, after 2 weeks (10 additional training sessions), and after 4 weeks (20 additional training sessions) of therapy. RESULTS: The combined treatment led to significant improvements in WM performance, verbal memory, and self-reported changes in daily life. The amount of training was identified to modulate efficacy: Significant improvements showed only in the later training phase. We observed no differences between the two training schemes (WM vs. attentional training). CONCLUSIONS: Even in the chronic phase after brain lesion WM performance can be enhanced by the combination of compensation therapy and computerized cognitive training when applied intensely; both a more general attention and a specific WM training regimen are effective.

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.

Dissociation of amyloid biomarkers in PET and CSF in Alzheimer's disease: a case report.

BACKGROUND: Recently, biomarkers have been suggested to be incorporated into diagnostic criteria for Alzheimer's disease (AD). Regarding disease-specific brain amyloid-beta deposition these comprise low amyloid-beta 1-42 in cerebrospinal fluid (CSF) and positive positron emission tomography (PET) amyloid imaging, while neuronal degeneration is evidenced by high total and phosphorylated tau levels in CSF (t-/p-tau), regional hypometabolism ([(18)F]fluorodeoxyglucose PET, FDG-PET) and characteristic atrophy-patterns (magnetic resonance imaging, MRI). CASE PRESENTATION: Here we present a case of clinically and biomarker supported AD (CSF t-/p-tau, MRI, FDG-PET) in a 59-year-old Caucasian man in whom indicators of amyloid-beta deposition dissociated between CSF parameters and the respective PET imaging. CONCLUSIONS: Such cases highlight the necessity to better understand potential dissociations between PET and CSF data for amyloid-beta biomarkers, because they are currently considered interchangeably valid with regard to in-vivo evidence for AD pathology. This is more important since amyloid deposition markers can be considered a very first prognostic indicator of imminent AD, prior to neurodegenerative biomarkers and cognitive symptoms. The case illustrates the need for further longitudinal data on potential dissociations of AD biomarkers to devise recommendations for their better prognostic and diagnostic interpretation in the future.

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.

Application of immersive virtual reality for assessing chronic neglect in individuals with stroke: the immersive virtual road-crossing task.

BACKGROUND: Neglect can be a long-term consequence of chronic stroke that can impede an individual's ability to perform daily activities, but chronic and discrete forms can be difficult to detect. We developed and evaluated the "immersive virtual road-crossing task" (iVRoad) to identify and quantify discrete neglect symptoms in chronic stroke patients. METHOD: The iVRoad task requires crossing virtual intersections and placing a letter in a mailbox placed either on the left or right. We tested three groups using the HTC Vive Pro Eye: (1) chronic right hemisphere stroke patients with (N = 20) and (2) without (N = 20) chronic left-sided neglect, and (3) age and gender-matched healthy controls (N = 20). We analyzed temporal parameters, errors, and head rotation to identify group-specific patterns, and applied questionnaires to measure self-assessed pedestrian behavior and usability. RESULTS: Overall, the task was well-tolerated by all participants with fewer cybersickness-induced symptoms after the VR exposure than before. Reaction time, left-sided errors, and lateral head movements for traffic from left most clearly distinguished between groups. Neglect patients committed more dangerous crossings, but their self-rated pedestrian behavior did not differ from that of stroke patients without neglect. This demonstrates their reduced awareness of the risks in everyday life and highlights the clinical relevance of the task. CONCLUSIONS: Our findings suggest that a virtual road crossing task, such as iVRoad, has the potential to identify subtle symptoms of neglect by providing virtual scenarios that more closely resemble the demands and challenges of everyday life. iVRoad is an immersive, naturalistic virtual reality task that can measure clinically relevant behavioral variance and identify discrete neglect symptoms.

Rehabilitation Services for Young-Onset Dementia: Examples from High- and Low-Middle-Income Countries.

The WHO Dementia Global Action Plan states that rehabilitation services for dementia are required to promote health, reduce disability, and maintain quality of life for those living with dementia. Current services, however, are scarce, particularly for people with young-onset dementia (YOD). This article, written by an international group of multidisciplinary dementia specialists, offers a three-part overview to promote the development of rehabilitation services for YOD. Firstly, we provide a synthesis of knowledge on current evidence-based rehabilitative therapies for early-onset Alzheimer's disease (EOAD), behavioural variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), and posterior cortical atrophy (PCA). Secondly, we discuss the characteristics of rehabilitation services for YOD, providing examples across three continents for how these services can be embedded in existing settings and the different roles of the rehabilitation multidisciplinary team. Lastly, we conclude by highlighting the potential of telehealth in making rehabilitation services more accessible for people with YOD. Overall, with this paper, we aim to encourage clinical leads to begin introducing at least some rehabilitation into their services, leveraging existing resources and finding support in the collective expertise of the broader multidisciplinary dementia professional community.

CORDIAL: cognitive rehabilitation and cognitive-behavioral treatment for early dementia in Alzheimer disease: a multicenter, randomized, controlled trial.

Cognitive rehabilitation (CR) is a promising treatment approach for older adults with dementia because it aims at supporting the management of day-to-day problems. There is insufficient evidence regarding whether CR provides clinically meaningful benefits. In this study, we evaluated the feasibility, acceptance, efficacy, and usefulness of a CR intervention in a multicenter, randomized, controlled trial on 201 patients with mild dementia in Alzheimer disease and their carers. The intervention comprised 12 individual weekly sessions and combined 4 established strategies adopted from neurorehabilitation and psychotherapy. Activities of daily living were chosen as the primary outcome. The results show that the feasibility, treatment adherence, and carer commitment were excellent. However, no effect of the intervention was demonstrable on everyday functioning. There were improvements favoring the intervention on quality of life and treatment satisfaction and a significant antidepressant effect in female participants. The lack of impact on everyday activities may be due to methodological limitations including insufficient personalization, short treatment duration, poor transfer into the real-life setting, and low sensitivity of assessment instruments. The findings of this study may be helpful for designing further studies that are needed to determine the potential of CR in older adults with dementia.

Neuropsychiatric phenotype of post COVID-19 syndrome in non-hospitalized patients.

The post COVID-19 syndrome (PCS) is an emerging phenomenon worldwide with enormous socioeconomic impact. While many patients describe neuropsychiatric deficits, the symptoms are yet to be assessed and defined systematically. In this prospective cohort study, we report on the results of a neuropsychiatric consultation implemented in May 2021. A cohort of 105 consecutive patients with merely mild acute course of disease was identified by its high symptom load 6 months post infection using a standardized neurocognitive and psychiatric-psychosomatic assessment. In this cohort, we found a strong correlation between higher scores in questionnaires for fatigue (MFI-20), somatization (PHQ15) and depression (PHQ9) and worse functional outcome as measured by the post COVID functional scale (PCFS). In contrast, neurocognitive scales correlated with age, but not with PCFS. Standard laboratory and cardiopulmonary biomarkers did not differ between the group of patients with predominant neuropsychiatric symptoms and a control group of neuropsychiatrically unaffected PCS patients. Our study delineates a phenotype of PCS dominated by symptoms of fatigue, somatisation and depression. The strong association of psychiatric and psychosomatic symptoms with the PCFS warrants a systematic evaluation of psychosocial side effects of the pandemic itself and psychiatric comorbidities on the long-term outcome of patients with SARS-CoV-2 infection.

Hippocampal gray matter volume in the long-term course after transient global amnesia.

OBJECTIVE: In this retrospective, cross-sectional study we aimed to examine long-term memory deficits and gray matter volumes (GMV) in the hippocampus after transient global amnesia (TGA). METHODS: 20 patients with a history of TGA (TGA+, mean 6.5 years after TGA) and 20 age-matched healthy controls (TGA-) underwent neurocognitive assessment (i.e. Mini-Mental State Examination (MMSE), visuospatial, verbal and episodic autobiographical memory and visuospatial learning/navigation ["human water maze"]) in combination with structural cerebral MRI. Voxel-based morphometry (VBM) was used to detect GMV in the hippocampus in TGA+ versus TGA-. RESULTS: Besides slight differences in MMSE and visuo-spatial learning/navigation measured with a human water maze in TGA+ vs. TGA-, no other tests of visuo-spatial, verbal and autobiographical long-term memory differed between groups. VBM analyses yielded a statistically significant difference in bilateral hippocampal GMV with TGA+ compared to TGA- showing greater GMV in a region corresponding to bilateral CA1. However, none of the hippocampus-dependent cognitive measures correlated with hippocampal GMV. CONCLUSION: In the long-term course after TGA, only subtle neurocognitive deficits without microstructural damage of the hippocampus could be detected. Greater GMV in bilateral hippocampus in TGA+ vs. TGA- may indicate that TGA triggers hippocampal GMV increase rather than atrophy.

A mind-brain-body dataset of MRI, EEG, cognition, emotion, and peripheral physiology in young and old adults.

We present a publicly available dataset of 227 healthy participants comprising a young (N=153, 25.1±3.1 years, range 20-35 years, 45 female) and an elderly group (N=74, 67.6±4.7 years, range 59-77 years, 37 female) acquired cross-sectionally in Leipzig, Germany, between 2013 and 2015 to study mind-body-emotion interactions. During a two-day assessment, participants completed MRI at 3 Tesla (resting-state fMRI, quantitative T1 (MP2RAGE), T2-weighted, FLAIR, SWI/QSM, DWI) and a 62-channel EEG experiment at rest. During task-free resting-state fMRI, cardiovascular measures (blood pressure, heart rate, pulse, respiration) were continuously acquired. Anthropometrics, blood samples, and urine drug tests were obtained. Psychiatric symptoms were identified with Standardized Clinical Interview for DSM IV (SCID-I), Hamilton Depression Scale, and Borderline Symptoms List. Psychological assessment comprised 6 cognitive tests as well as 21 questionnaires related to emotional behavior, personality traits and tendencies, eating behavior, and addictive behavior. We provide information on study design, methods, and details of the data. This dataset is part of the larger MPI Leipzig Mind-Brain-Body database.

WOME: Theory-Based Working Memory Training - A Placebo-Controlled, Double-Blind Evaluation in Older Adults.

Background: Scientifically evaluated cognitive intervention programs are essential to meet the demands of our increasingly aging society. Currently, one of the "hottest" topics in the field is the improvement of working memory function and its potential impact on overall cognition. The present study evaluated the efficacy of WOME (WOrking MEmory), a theory-based working memory training program, in a double-blind, placebo-controlled, and randomized controlled trial (www.drks.de, DRKS00013162). Methods:N = 60 healthy older adults were allocated to (1) the WOME intervention, (2) an active low-level intervention, or (3) a passive control group. Overall, the intervention groups practiced twelve sessions of 45 min within 4 weeks of their respective training. Transfer effects were measured via an extensive battery of neuropsychological tests and questionnaires both pre-/post-training and at a 3-month follow-up. Results:WOME led to a significant improvement in working memory function, demonstrated on a non-trained near transfer task and on two different composite scores with moderate to large effect sizes. In addition, we found some indication of relevant impact on everyday life. The effects were short-term rather than stable, being substantially diminished at follow-up with only little evidence suggesting long-term maintenance. No transfer effects on other cognitive functions were observed. Conclusion:WOME is an appropriate and efficient intervention specifically targeting the working memory system in healthy older adults. Trial Registration: German Clinical Trials Register (DRKS), Identifier: DRKS00013162.

A Modified Reading the Mind in the Eyes Test Predicts Behavioral Variant Frontotemporal Dementia Better Than Executive Function Tests.

Behavioral variant frontotemporal dementia (bvFTD) is characterized by deep alterations in behavior and personality. Although revised diagnostic criteria agree for executive dysfunction as most characteristic, impairments in social cognition are also suggested. The study aimed at identifying those neuropsychological and behavioral parameters best discriminating between bvFTD and healthy controls. Eighty six patients were diagnosed with possible or probable bvFTD according to Rascovsky et al. (2011) and compared with 43 healthy age-matched controls. Neuropsychological performance was assessed with a modified Reading the Mind in the Eyes Test (RMET), Stroop task, Trail Making Test (TMT), Hamasch-Five-Point Test (H5PT), and semantic and phonemic verbal fluency tasks. Behavior was assessed with the Apathy Evaluation Scale, Frontal Systems Behavioral Scale, and Bayer Activities of Daily Living Scale. Each test's discriminatory power was investigated by Receiver Operating Characteristic curves calculating the area under the curve (AUC). bvFTD patients performed significantly worse than healthy controls in all neuropsychological tests. Discriminatory power (AUC) was highest in behavioral questionnaires, high in verbal fluency tasks and the RMET, and lower in executive function tests such as the Stroop task, TMT and H5PT. As fluency tasks depend on several cognitive functions, not only executive functions, results suggest that the RMET discriminated better between bvFTD and control subjects than other executive tests. Social cognition should be incorporated into diagnostic criteria for bvFTD in the future, such as in the International Classification of Diseases (ICD)-11, as already suggested in the Diagnostic and Statistical Manual for Mental Disorders (DSM)-5.

Neurocognition and Cerebral Lesion Burden in High-Risk Patients Before Undergoing Transcatheter Aortic Valve Replacement: Insights From the SENTINEL Trial.

OBJECTIVES: The authors sought to determine baseline neurocognition before transcatheter aortic valve replacement (TAVR) and its correlations with pre-TAVR brain imaging. BACKGROUND: TAVR studies have not shown a correlation between diffusion-weighted image changes and neurocognition. The authors wanted to determine the extent to which there was already impairment at baseline that correlated with cerebrovascular disease. METHODS: SENTINEL (Cerebral Protection in Transcatheter Aortic Valve Replacement) trial patients had cognitive assessments of attention, processing speed, executive function, and verbal and visual memory. Z-scores were based on normative means and SDs, combined into a primary composite z-score. Brain magnetic resonance images were obtained pre-TAVR on 3-T scanners with a T2 fluid-attenuated inversion recovery (FLAIR) sequence. Scores ≤-1.5 SD below the normative mean (7th percentile) were considered impairment. Paired t tests compared within-subject scores, and chi-square goodness-of-fit compared the percentage of subjects below -1.5 SD. Correlation and regression analyses assessed the relationship between neurocognitive z-scores and T2 lesion volume. RESULTS: Among 234 patients tested, the mean composite z-score was -0.65 SD below the normative mean. Domain scores ranged from -0.15 SD for attention to -1.32 SD for executive function. On the basis of the ≥1.5 SD normative reference, there were significantly greater percentages of impaired scores in the composite z-score (13.2%; p = 0.019), executive function (41.9%; p < 0.001), verbal memory (p < 0.001), and visual memory (p < 0.001). The regression model between FLAIR lesion volume and baseline cognition showed statistically significant negative correlations. CONCLUSIONS: There was a significant proportion of aortic stenosis patients with impaired cognition before TAVR, with a relationship between baseline cognitive function and lesion burden likely attributable to longstanding cerebrovascular disease. These findings underscore the importance of pre-interventional testing and magnetic resonance imaging in any research investigating post-surgical cognitive outcomes in patients with cardiovascular disease.

Can impaired working memory functioning be improved by training? A meta-analysis with a special focus on brain injured patients.

OBJECTIVE: Deficits in working memory (WM) are commonly observed after brain injuries and cause severe impairments in patients' everyday life. It is still under debate if training can enhance or rehabilitate WM in case of malfunction. The current meta-analysis investigates this issue from a clinical point of view. It addresses under which conditions and for which target group WM training may be justifiable. METHOD: Relevant WM training studies were identified by searching electronic literature databases with a comprehensive search term. In total, 103 studies, which added up to 112 independent group comparisons (N = 6,113 participants), were included in the analysis. RESULTS: Overall, WM training caused a moderate and long-lasting improvement in untrained WM tasks. Moreover, improvement of WM functioning led to sustainable better evaluation of everyday life functioning, however, effect sizes were small. Concerning transfer effects on other cognitive domains, long-lasting improvements with small effect sizes were observed in cognitive control and reasoning/intelligence. In contrast, small immediate, but no long-term effects were found for attention and long-term memory. Studies with brain injured patients demonstrated long-lasting improvements in WM functions with moderate to large effect sizes. A main moderator variable of intervention efficacy is the number of training sessions applied. CONCLUSION: WM training produces long-lasting beneficial effects which are strongly pronounced in patients with acquired brain injuries. This finding supports the application of WM training in clinical settings. To determine optimal training conditions, future studies must systematically investigate the characteristics of interventions as they are at present inevitably confounded.

Focal retrograde amnesia: voxel-based morphometry findings in a case without MRI lesions.

Focal retrograde amnesia (FRA) is a rare neurocognitive disorder presenting with an isolated loss of retrograde memory. In the absence of detectable brain lesions, a differentiation of FRA from psychogenic causes is difficult. Here we report a case study of persisting FRA after an epileptic seizure. A thorough neuropsychological assessment confirmed severe retrograde memory deficits while anterograde memory abilities were completely normal. Neurological and psychiatric examination were unremarkable and high-resolution MRI showed no neuroradiologically apparent lesion. However, voxel-based morphometry (VBM)-comparing the MRI to an education-, age-and sex-matched control group (n = 20) disclosed distinct gray matter decreases in left temporopolar cortex and a region between right posterior parahippocampal and lingual cortex. Although the results of VBM-based comparisons between a single case and a healthy control group are generally susceptible to differences unrelated to the specific symptoms of the case, we believe that our data suggest a causal role of the cortical areas detected since the retrograde memory deficit is the preeminent neuropsychological difference between patient and controls. This was paralleled by grey matter differences in central nodes of the retrograde memory network. We therefore suggest that these subtle alterations represent structural correlates of the focal retrograde amnesia in our patient. Beyond the implications for the diagnosis and etiology of FRA, our results advocate the use of VBM in conditions that do not show abnormalities in clinical radiological assessment, but show distinct neuropsychological deficits.

Reduced daytime activity in patients with acquired brain damage and apathy: a study with ambulatory actigraphy.

PRIMARY OBJECTIVE: Apathy is difficult to assess in clinical practice. Ambulatory actigraphy was used with the aim to measure locomotor activity during the daytime as a correlate of self-initiated action in brain-damaged patients with apathy. RESEARCH DESIGN: Twenty-four patients with acquired brain damage and high levels of apathy or low levels of apathy as well as 12 healthy controls were investigated using a parallel group design. METHODS AND PROCEDURES: Apathy was diagnosed after clinical observation and evaluated with the apathy evaluation scale. Locomotor activity was measured with a wrist-worn actigraph over 3 days. RESULTS: High apathy patients showed significantly reduced locomotor activity and more episodes of inactivity (naps) during the daytime. Self-rated apathy correlated with daytime activity, nap frequency and cognitive (executive) deficits. CONCLUSIONS: Ambulatory actigraphy is a promising method to evaluate self-initiated action in patients with apathy.

Planning and realization of complex intentions in traumatic brain injury and normal aging.

The realization of delayed intentions (i.e., prospective memory) is a highly complex process composed of four phases: intention formation, retention, re-instantiation, and execution. The aim of this study was to investigate if executive functioning impairments are related to problems in the formation, re-instantiation, and execution of a delayed complex intention. In this context, it was another aim of the study to investigate the executive functioning hypothesis of cognitive aging in prospective memory performance. It was, therefore, explored if age-related prospective memory decline leads to similar decrements in the process of prospective remembering as executive functioning-related decline in young patients with traumatic brain injury. A group of patients with traumatic brain injury with retrospective memory within normal limits but impaired executive functions, a group of healthy older and a group of healthy younger adults completed a complex prospective memory task that allows for the separate assessment of the four phases of the prospective memory process. All groups showed a similarly high performance in the intention retention phase, whereas the patients with deficits in executive functioning and the older participants performed worse than the healthy young participants in the intention formation, re-instantiation and execution phases. The importance of executive functioning for prospective remembering in traumatic brain injury and normal aging is discussed.