Lost in spatial translation - A novel tool to objectively assess spatial disorientation in Alzheimer's disease and frontotemporal dementia

Spatial disorientation is a prominent feature of early Alzheimer's disease (AD) attributed to degeneration of medial temporal and parietal brain regions, including the retrosplenial cortex (RSC). By contrast, frontotemporal dementia (FTD) syndromes show generally intact spatial orientation at presentation. However, currently no clinical tasks are routinely administered to objectively assess spatial orientation in these neurodegenerative conditions. In this study we investigated spatial orientation in 58 dementia patients and 23 healthy controls using a novel virtual supermarket task as well as voxel-based morphometry (VBM). We compared performance on this task with visual and verbal memory function, which has traditionally been used to discriminate between AD and FTD. Participants viewed a series of videos from a first person perspective travelling through a virtual supermarket and were required to maintain orientation to a starting location. Analyses revealed significantly impaired spatial orientation in AD, compared to FTD patient groups. Spatial orientation performance was found to discriminate AD and FTD patient groups to a very high degree at presentation. More importantly, integrity of the RSC was identified as a key neural correlate of orientation performance. These findings confirm the notion that i) it is feasible to assess spatial orientation objectively via our novel Supermarket task; ii) impaired orientation is a prominent feature that can be applied clinically to discriminate between AD and FTD and iii) the RSC emerges as a critical biomarker to assess spatial orientation deficits in these neurodegenerative conditions

Testing Spatial Cognition in Mild Cognitive Impairment Using Immersive Virtual Reality

The prodromal stage of dementia is known as mild cognitive impairment (MCI). Currently, cognitive tests are unable to correctly characterize the MCI type, and specifically, whether it will develop into Alzheimer's disease (AD). This means that cognitive deficits are detected long after the onset of pathological changes. More sensitive and specific tests, which can non-invasively detect the subtle, early signs of AD in MCI, would facilitate investigation of its early development and potentially permit early treatments. This thesis aims to develop a diagnostic tool to target the cognitive functions – and engage the corresponding brain regions – typically affected during the prodromal stages of AD. Pathological changes start in the hippocampal formation, a critical area for episodic memory and navigation. The tasks are developed from previous work demonstrating hippocampal dependence and make use of recent advances in immersive virtual reality, providing an ecologically valid improvement on standard tests of cognitive function. The first experimental chapter presents a test of navigation by path integration, a function specifically associated with processing by grid cells in the medial entorhinal cortex (mEC). The second experiment presents a test of object-location memory, believed to involve place cells in the hippocampus proper, combining inputs from mEC and object-identity information from the lateral entorhinal cortex (lEC). The third experiment tests object-location memory in a way that enables the contribution of self-motion to be assessed. Results show that the immersive virtual reality paradigms developed to test spatial cognition in prodromal AD are able to differentiate MCI patients from healthy age-matched older controls. Additionally, in combination with CSF biomarkers, navigation testing has proven the ability to stratify between MCI with different levels of biomarkers, identifying the patients who are most likely going to develop the disease. Finally, the last experiment, in an attempt to summarize different aspects of spatial cognition tested in the previous experiments, can detect subtle changes starting from ageing that may further decline with the onset of cognitive decline due to AD neuropathology. In conclusion within this thesis, we demonstrated the use of immersive virtual reality tests as an ecological valid tool for assessing the behavioural changes associated with the early progression of AD

Path Integration Changes as a Cognitive Marker for Vascular Cognitive Impairment?—A Pilot Study

Path integration spatial navigation processes are emerging as promising cognitive markers for prodromal and clinical Alzheimer’s disease (AD). However, such path integration changes have been less explored in Vascular Cognitive Impairment (VCI), despite neurovascular change being a major contributing factor to dementia and potentially AD. In particular, the sensitivity and specificity of path integration impairments in VCI compared to AD is unclear. In the current pilot study, we explore path integration performance in early-stage AD and VCI patient groups and hypothesize that: (i) medial parietal mediated egocentric processes will be more affected in VCI; and (ii) medial temporal mediated allocentric processes will be more affected in AD. This cross-sectional study included early-stage VCI patients (n = 9), AD patients (n = 10) and healthy age-matched controls (n = 20). All participants underwent extensive neuropsychological testing, as well as spatial navigation testing. The spatial navigation tests included the virtual reality “Supermarket” task assessing egocentric (body-based) and allocentric (map-based) navigation as well as the “Clock Orientation” test assessing egocentric and path integration processes. Results showed that egocentric integration processes are only impaired in VCI, potentially distinguishing it from AD. However, in contrast to our prediction, allocentric integration was not more impaired in AD compared to VCI. These preliminary findings suggest limited specificity of allocentric integration deficits between VCI and AD. By contrast, egocentric path integration deficits emerge as more specific to VCI, potentially allowing for more specific diagnostic and treatment outcome measures for vascular impairment in dementia

"Enriching 360-degree technologies through human-computer interaction: psychometric validation of two memory tasks"

This doctoral dissertation explores the domain of neuropsychological assessment, with the objective of gaining a comprehensive understanding of an individual's cognitive functioning and detecting possible impairments. Traditional assessment tools, while possessing inherent value, frequently exhibit a deficiency in ecological validity when evaluating memory, as they predominantly concentrate on short-term, regulated tasks. To overcome this constraint, immersive technologies, specifically virtual reality and 360° videos, have surfaced as promising instruments for augmenting the ecological validity of cognitive assessments. This work examines the potential advantages of immersive technologies, particularly 360° videos, in enhancing memory evaluation. First, a comprehensive overview of contemporary virtual reality tools employed in the assessment of memory, as well as their convergence with conventional assessment measures has been provided. Then, the present study utilizes cluster and network analysis techniques to categorize 360° videos according to their content and applications, thereby offering significant insights into the potential of this nascent medium. The study introduces then a novel platform, Mindscape, that aims to address the existing technological disparity, thereby enhancing the accessibility of clinicians and researchers in developing cognitive tasks within immersive environments. The conclusion of the thesis encompasses the psychometric validation of two memory tasks, which have been specifically developed with Mindscape to assess episodic and spatial memory. The findings demonstrate disparities in cognitive performance between individuals diagnosed with Mild Cognitive Impairment and those without cognitive impairments, underscoring the interrelated nature of cognitive processes and the promising prospects of virtual reality technology in improving the authenticity of real-world experiences. Overall, this dissertation aims to respond to the demand for practical and ecologically valid neuropsychological assessments within the dynamic field of neuropsychology. It achieves this by integrating user-friendly platforms and immersive cognitive tasks into its methodology. By highlighting a shift in the field of neuropsychology towards prioritizing functional and practical assessments over theoretical frameworks, this work indicates a changing perspective within the discipline. This study highlights the potential of comprehensive and purpose-oriented assessment methods in cognitive evaluations, emphasizing the ongoing significance of research in fully comprehending the capabilities of immersive technologies

Being in the Past and Perform the Future in a Virtual World: VR Applications to Assess and Enhance Episodic and Prospective Memory in Normal and Pathological Aging

The process of aging commonly features a gradual deterioration in cognitive performance and, in particular, the decline of memory. Despite the increased longevity of the world's population, the prevalence of neurodegenerative conditions, such as dementia, continues to be a major burden on public health, and consequently, the latest research has been focused on memory and aging. Currently, the failure of episodic and Prospective memory (PM) is one of the main complaints in the elderly, considered among the early symptoms of dementia. It is therefore increasingly important to define more clearly the boundaries between normal and pathological aging. Recently, researchers have begun to build and apply Virtual Environments (VE) to the explicit purpose of better understanding the performance of episodic and PM in complex and realistic contexts, with the perspective of further developing effective training procedures that depend on reliable cognitive assessment methods. Virtual technology offers higher levels of realism than "pen and paper" testing and at the same time more experimental control than naturalistic settings. In this mini-review article, we examine the outcomes of recently available studies on virtual reality technology applications developed for the assessment and improvement of episodic and/or PM. To consider the latest technology, we selected 29 articles that have been published in the last 10 years. These documents show that VR-based technologies can provide a valid basis for screening and treatment and, through increased sensory stimulation and enriched environments reproducing the scenarios of everyday life, could represent effective stimulating experiences even in pathological aging

Validation of the Virtual Reality Everyday Assessment Lab (VR-EAL):An immersive virtual reality neuropsychological battery with enhanced ecological validity

International audienceObjective: The assessment of cognitive functions such as prospective memory, episodic memory, attention, and executive functions benefits from an ecologically valid approach to better understand how performance outcomes generalize to everyday life. Immersive virtual reality (VR) is considered capable of simulating real-life situations to enhance ecological validity. The present study attempted to validate the Virtual Reality Everyday Assessment Lab (VR-EAL), an immersive VR neuropsychological battery, against an extensive paper-andpencil neuropsychological battery. Methods: Forty-one participants (21 females) were recruited: 18 gamers and 23 non-gamers who attended both an immersive VR and a paper-and-pencil testing session. Bayesian Pearson correlation analyses were conducted to assess construct and convergent validity of the VR-EAL. Bayesian t-tests were performed to compare VR and paper-and-pencil testing in terms of administration time, similarity to real life tasks (i.e., ecological validity), and pleasantness. Results: VR-EAL scores were significantly correlated with their equivalent scores on the paper-and-pencil tests. The participants' reports indicated that the VR-EAL tasks were significantly more ecologically valid and pleasant than the paper-and-pencil neuropsychological battery. The VR-EAL battery also had a shorter administration time. Conclusion: The VR-EAL appears as an effective neuropsychological tool for the assessment of everyday cognitive functions, which has enhanced ecological validity, a highly pleasant testing experience, and does not induce cybersickness

Spatial navigation deficits — overlooked cognitive marker for preclinical Alzheimer disease?

Detection of incipient Alzheimer disease (AD) pathophysiology is critical to identify preclinical individuals and target potentially disease-modifying therapies towards them. Current neuroimaging and biomarker research is strongly focused in this direction, with the aim of establishing AD fingerprints to identify individuals at high risk of developing this disease. By contrast, cognitive fingerprints for incipient AD are virtually non-existent as diagnostics and outcomes measures are still focused on episodic memory deficits as the gold standard for AD, despite their low sensitivity and specificity for identifying at-risk individuals. This Review highlights a novel feature of cognitive evaluation for incipient AD by focusing on spatial navigation and orientation deficits, which are increasingly shown to be present in at-risk individuals. Importantly, the navigation system in the brain overlaps substantially with the regions affected by AD in both animal models and humans. Notably, spatial navigation has fewer verbal, cultural and educational biases than current cognitive tests and could enable a more uniform, global approach towards cognitive fingerprints of AD and better cognitive treatment outcome measures in future multicentre trials. The current Review appraises the available evidence for spatial navigation and/or orientation deficits in preclinical, prodromal and confirmed AD and identifies research gaps and future research priorities

The cupboard task: An immersive virtual reality-based system for everyday memory assessment

Background and objective Virtual Reality (VR) has the capacity to be used in cognitive rehabilitation interventions for diagnostic and training purposes. This technology allows the development of proposals that traditionally have been only implemented using physical elements that imply greater resources and a lesser degree of automation. This work presents an immersive virtual reality (IVR) application (the Cupboard task) for the evaluation of memory in a more ecological way and based on an activity of daily living (ADL). Methods To appraise its construct validity, we have carried out a comparative study with a traditional method of memory assessment (method of loci). To check for any association between performance and age, performance with years of education, and reaction time with age, the Pearson's correlation was used. One-way ANOVA was used to check for differences in performance by gender. We also performed a reliability analysis with a two way mixed effects model where people effects are random and measures effects are fixed. Therefore, intra-class correlation coefficient with absolute agreement was reckoned to assess the consistency or concordance of the measures made by both the method of loci and the cupboard IVR task. Results Both tasks were evaluated on a sample of 22 healthy participants who voluntarily took part in the experiment. The results obtained showed a high degree of concordance between both memory performance measures, which assumes good clinical relevance. In addition, other age-related effects were found, common to memory assessment tasks. Conclusions This work showed that it is possible to use an IVR application to successfully assess everyday memory. We have also demonstrated the potential of IVR to develop valid tests that assess memory functions reliably and efficiently and within ecologically valid contexts. The results obtained open the door to its use in clinical settings for cognitive training (and promoting cognitive health) of patients with mild cognitive impairment (MCI), severe cognitive impairment (SCI) such as Alzheimer or Dementia, etc., with full guarantees of application, although it must first be validated through a randomized control trial (RCT). The degree of usability of the Cupboard task was very high according to the test carried out by the participants