Literature Review

The role of egocentric and allocentric abilities in Alzheimer's disease: A systematic review

Article· Literature ReviewinAgeing Research Reviews 16:32-44 · June 2014with 586 Reads
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  • Article
    Topographical disorientation refers to inability to recognize the environment, as well as to orient, to find the right way into a familiar or new environment and to use a map for the orientation. These functions are based on neuronal activity of posterior parietal cortex, retrosplenial cortex and the posterior part of cingular gyrus, medial temporal lobe, lingual gyrus and prefrontal cortex and are considered within egocentric or allocentric (exocentric) reference systems. Object locations in the egocentric system are evaluated with respect to the subject’s body position while object locations in the allocentric reference frame are evaluated with respect to the object-to-object relations in the external environment. Topographical orientation disorders are observed in local lesions of the brain and in neurodegenerative diseases. The topographical disorientation may be due to landmark аgnosia, egocentric disorientation, heading disorientation and anterograde disorientation. Clinical tests for the diagnosis of topographical disorientation include blanket methods and navigation tasks in real or virtual space. The restorative and compensatory strategies are used in rehabilitation of patients with topographical disorientation. Clarification of the general strategy and selection of the optimal neurorehabilitation methods depend on the causes and severity of brain lesions.
  • Article
    Full-text available
    A growing body of evidence pointed out that a decline in effectively using spatial reference frames for categorizing information occurs both in normal and pathological aging. Moreover, it is also known that executive deficits primarily characterize the cognitive profile of older individuals. Acknowledging this literature, the current study was aimed to specifically disentangle the contribution of the cognitive abilities related to the use of spatial reference frames to executive functioning in both healthy and pathological aging. 48 healthy elderly individuals and 52 elderly suffering from probable Alzheimer's Disease (AD) took part in the study. We exploited the potentiality of Virtual Reality to specifically measure the abilities in retrieving and syncing between different spatial reference frames, and then we administrated different neuropsychological tests for evaluating executive functions. Our results indicated that allocentric functions contributed significantly to the planning abilities, while syncing abilities influenced the attentional ones. The findings were discussed in terms of previous literature exploring relationships between cognitive deficits in the first phase of AD.
  • Article
    Full-text available
    Objective: Deficits in egocentric (subject-to-object) and allocentric (object-to-object) spatial representations, with a mainly allocentric impairment, characterize the first stages of the Alzheimer's disease (AD). Methods: To identify early cognitive signs of AD conversion, some studies focused on amnestic-Mild Cognitive Impairment (aMCI) by reporting alterations in both reference frames, especially the allocentric ones. However, spatial environments in which we move need the cooperation of both reference frames. Such cooperating processes imply that we constantly switch from allocentric to egocentric frames and vice versa. This raises the question of whether alterations of switching abilities might also characterize an early cognitive marker of AD, potentially suitable to detect the conversion from aMCI to dementia. Here, we compared AD and aMCI patients with Normal Controls (NC) on the Ego-Allo-Switching spatial memory task. The task assessed the capacity to use switching (Ego-Allo, Allo-Ego) and non-switching (Ego-Ego, Allo-Allo) verbal judgments about relative distances between memorized stimuli. The novel finding of this study is the neat impairment shown by aMCI and AD in switching from allocentric to egocentric reference frames. Interestingly, in aMCI when the first reference frame was egocentric, the allocentric deficit appeared attenuated. Conclusion: This led us to conclude that allocentric deficits are not always clinically detectable in aMCI since the impairments could be masked when the first reference frame was body-centred. Alongside, AD and aMCI also revealed allocentric deficits in the non-switching condition. These findings suggest that switching alterations would emerge from impairments in hippocampal and posteromedial areas and from concurrent dysregulations in the locus coeruleus-noradrenaline system or pre-frontal cortex.
  • Article
    Full-text available
    Sporadic Alzheimer's disease (AD) is the most prevalent form of age-related dementia. As such, great effort has been put forth to investigate the etiology, progression, and underlying mechanisms of the disease. Countless studies have been conducted, however, the details of this disease remain largely unknown. Rodent models provide opportunities to investigate certain aspects of AD that cannot be studied in humans. These animal models vary from study to study and have provided some insight, but no real advancements in the prevention or treatment of the disease. In this Hypothesis and Theory paper, we discuss what we perceive as barriers to impactful discovery in rodent AD research and we offer potential solutions for moving forward. Although no single model of AD is capable of providing the solution to the growing epidemic of the disease, we encourage a comprehensive approach that acknowledges the complex etiology of AD with the goal of enhancing the bidirectional translatability from bench to bedside and vice versa.
  • Article
    Background: The present study explores recent and well-consolidated spatial memory within the egocentric and allocentric frames of reference in young and elderly people. Methods: The research included young and old participants, within the range of normality. All the participants were tested on four spatial tasks requiring allocentric and egocentric judgments, based on recent as well as remote spatial information, using a Multivariate Regression Analysis. Results: An age effect on both egocentric and allocentric tasks was present in recently learned spatial information. The age effect was not present in tasks regarding well-consolidated spatial information. Finally, sex influenced the performance in allocentric tasks regarding both recent and well-consolidated memory. Conclusion: These data were discussed according to the Multiple Trace Theory, supporting the idea that the magnitude of difference between egocentric and allocentric judgments in aging is somewhat attributable to the characteristic of spatial tasks. In general, a lower difference between the performance of young and elderly participants is shown in tasks based on well-consolidated information when compared with tasks based on episodic information. Well-consolidated information seemed to be better preserved in memory and less prone to the impairment.
  • Article
    Objective: The present study analyzes the age-related differences in map learning between young and normally-aging young-old and old-old adults in relation to individual visuo-spatial factors to specify which aspects of spatial learning are susceptible to aging. Methods: Forty young, 40 young-old and 40 old-old participants performed a series of tasks to assess their visuo-spatial working memory (VSWM) and visuo-spatial (rotation) abilities, then they studied a map. To test their recall, they graphically reproduced the map in a freehand drawing, then performed a sketch map task (which involved placing a list of landmarks on a blank layout of the map) and a pointing task (adopting aligned and counter-aligned imaginary positions). Conclusion: The results showed that age-related differences depend on the type of recall task performed: in the pointing and freehand map-drawing tasks, the young-old and old-old performed worse than the young adults; but in the sketch map task, the young-old performed as well as the young adults and only the old-old's performance was worse than that of the other two age groups. Concerning the role of individual factors, VSWM and rotation abilities were found strongly involved in the pointing task (especially for counter-aligned pointing) and the freehand map-drawing task. Overall, these results suggest that different factors related to spatial (map) learning explain age-related differences in normal aging. The implications of the present results in normal and pathological aging, and for the purposes of clinical assessments and interventions, are discussed.
  • Article
    Full-text available
    Aging affects many aspects of everyday living, such as autonomy, security and quality of life. Among all, spatial memory and spatial navigation show a gradual but noticeable decline, as a result of both neurobiological changes and the general slowing down of cognitive functioning. We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to identify studies that specifically investigated the role of allocentric and egocentric frames in healthy aging. Concerning spatial navigation, our results showed a preservation of egocentric strategies, along with specific impairments in the use of allocentric and switching abilities. Regarding spatial memory, instead, outcomes were more divergent and not frame-specific. With this perspective, spatial impairments were discussed considering the cognitive profile of mild cognitive impairment (MCI) and Alzheimer’s Disease (AD).
  • Article
    Full-text available
    A growing body of evidence suggests that people with Alzheimer's Disease (AD) show compromised spatial abilities. In addition, there exists from the earliest stages of AD a specific impairment in “mental frame syncing,” which is the ability to synchronize an allocentric viewpoint-independent representation (including object-to-object information) with an egocentric one by computing the bearing of each relevant “object” in the environment in relation to the stored heading in space (i.e., information about our viewpoint contained in the allocentric viewpoint-dependent representation). The main objective of this development-of-concept trial was to evaluate the efficacy of a novel VR-based training protocol focused on the enhancement of the “mental frame syncing” of the different spatial representations in subjects with AD. We recruited 20 individuals with AD who were randomly assigned to either “VR-based training” or “Control Group.” Moreover, eight cognitively healthy elderly individuals were recruited to participate in the VR-based training in order to have a different comparison group. Based on a neuropsychological assessment, our results indicated a significant improvement in long-term spatial memory after the VR-based training for patients with AD; this means that transference of improvements from the VR-based training to more general aspects of spatial cognition was observed. Interestingly, there was also a significant effect of VR-based training on executive functioning for cognitively healthy elderly individuals. In sum, VR could be considered as an advanced embodied tool suitable for treating spatial recall impairments.
  • Article
    Spatial navigation tasks reveal small differences between normal and pathological aging and may thus disclose potential neuropsychological predictors of neurodegenerative diseases. The aim of our study was to investigate which navigational skills are compromised in the early phase of pathological aging as well as the extent to which they are compromised. We performed an extensive neuropsychological evaluation based on working memory and learning tasks (i.e., Corsi Block-Tapping Test and Walking Corsi Test) involving both reaching and navigational vista spaces. We also assessed spatial navigation skills in the real world by asking participants to perform route-learning and landmark-recognition tasks. We conducted a cross-sectional study on nineteen patients with a diagnosis of mild cognitive impairment (MCI) who displayed either an isolated memory deficit (single-domain amnestic MCI, MCIsd; N=3) or a memory deficit associated with deficits in other cognitive functions (multi-domain MCI, MCImd; N=16) as well as on nineteen healthy control participants. The groups' performances were compared by means of mixed factorial ANOVA and two-sample t-tests. We found that patients with MCI performed worse than controls, especially when they were required to learn spatial positions within the navigational vista space. Route-learning within the real environment was also impaired whereas landmark-recognition was spared. The same pattern of results emerged in the MCImd subgroup. Moreover, single case analyses on MCIsd patients revealed a dissociation between learning of spatial positions within navigational vista space and within reaching space. These results suggest that topographical learning is compromised in the early phase of MCIsd and MCImd and that spatial navigation tasks may be used to better characterize topographical disorientation in MCI patients as well as for the early diagnosis of pathological aging.
  • Article
    Objective Topographical disorientation is a frequent issue in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Such impairments are replicated with virtual reality analogs of large-scale spatial navigation tasks. Objective: to evaluate whether visual cues are helpful for virtual spatial navigation and memory in AD and MCI patients. Material/patients and methods Twenty AD patients, 18 MCI patients and 20 age-matched healthy controls (HC) were included. All the participants had to reproduce actively a path including 5 intersections with one landmark at each that they had seen before passively. Three cueing conditions for navigation were proposed: salient landmarks, directional arrows and a map. A path without visual cues served as control condition. Navigation time and number of trajectory mistakes were recorded. After navigation, free recall and recognition of landmarks, landmarks ordering, choice of direction at each intersection and choice of patho outline were assessed. Results With the presence of directional arrows, no significant difference was found between groups concerning the number of trajectory mistakes and navigation time. The number of trajectory mistakes did not differ significantly between AD patients and MCI patients on the path with arrows, the path with salient landmarks and the path with a map. There were significant correlations between the number of trajectory mistakes under the arrow condition and executive tests (TMT and FAB), and between the number of trajectory mistakes under the salient landmark condition and memory tests (FCSRT 16 items and forward verbal span). Discussion – conclusion Visual cueing such as directional arrows and salient landmarks appears helpful for spatial navigation and memory tasks in AD and MCI patients. These visual cueing offers new research avenues for neurorehabilitation, such as the use of augmented reality in real-life settings to support the navigational capabilities of MCI and AD patients.
  • Article
    Full-text available
    Bodily awareness is a central component of human sensation, action, and cognition. The human body is subject to profound changes over the adult lifespan. We live in an aging society: the mean age of people living in industrialized countries is currently over 40 years, and further increases are expected. Nevertheless, there is a lack of comprehensive knowledge that links changes in embodiment that occur with age to neuronal mechanisms and associated sensorimotor and cognitive deficits in the elderly. Here, we synthesize existing evidence and introduce the NFL Framework of Embodied Aging, which links basic neuronal (N) mechanisms of age-related sensorimotor decline to changes in functional (F) bodily impairments, including deficits in higher-level cognitive functions, and impairments in daily life (L). We argue that cognitive and daily life impairments associated with old age are often due to deficits in embodiment, which can partly be linked to neuronal degradation at the sensorimotor level. The framework may encourage the development of novel approaches to improve autonomous living for the elderly.
  • Article
    Full-text available
    In the last decade, embodiment has dramatically influenced our conception of cognition. In this new frame, episodic memory, and particularly memory decline have been reinterpreted. Interventions supporting memory in the aging population address the connection between mind and body. Here, we discuss the use of Virtual Reality (VR) as an innovative tool to support episodic memory in older adults.
  • Article
    Topographical disorientation, the inability to orient in a well-known environment, is a very incapacitating syndrome. Despite its relatively high frequency after a right cerebral lesion, there is currently no specific neuropsychological test to assess it. We propose a completely new test, with preliminary normative data, assessing the subjects' ability to recall allocentric spatial information from their cognitive map. The subjects are asked to mentally compare distances and directions between landmarks in their familiar environment. This necessitates creating an individual version of the test tailored to every participant's knowledge. This task was proposed to 53 patients with a right lesion and a control group (N = 133). We evaluated performance at comparing distances and directions, and the impact of sociodemographic variables (age, gender, and education). Results show that a right cerebral lesion leads to difficulties in evoking and comparing allocentric spatial information, and more specifically in judging directions. Furthermore, the results show an impact of age, but not gender nor education, on recalling information from a cognitive map. Although there are some intrinsic difficulties (for example in creating patient-specific versions of the test), preliminary normative data indicate that this original test is workable and provides important information in assessing topographical disorientation in clinical practice.
  • Conference Paper
    Full-text available
    In the last decades, virtual reality environments are largely used in cognitive neuroscience research in order to provide participants with the possibility to navigate a space while brain activity is scanned through neuroimaging techniques such as MRI and similar. Accordingly in the field of spatial cognition research, several publications strongly assume the equivalence between exploring a not simulated and a computer-simulated environment. Albeit considering, since its first introduction in cognitive research, virtual reality simulation as an interesting possibility to study spatial knowledge organization, in the present paper I would like to address an “unrevealed question”: is it reasonable to obtain the same conclusions about spatial cognition from classical neuropsychological tests and virtual reality simulations? Or are there any differences for spatial knowledge acquisition provided from the simulations’ characteristics that we have to strongly consider? The main aim of this contribution is to find a possible answer to this question by introducing an embodied cognition approach to the study of wayfinding.
  • Article
    The ability to find one's way in the world, known as wayfinding, is impaired in individuals with Alzheimer's disease (AD). Older adult residential environments (e.g., independent living, assisted living, nursing home residences) are often especially difficult for wayfinding, with long, non-distinctive hallways and poorly differentiated routes. Wayfinding problems can cause anxiety, distress, and decreased interaction in individuals with dementia. Visual cues are one promising intervention to help this population find their way more easily. The current article reviews research studies that examine the influence of visual cues on wayfinding. The literature shows evidence that individuals with AD have difficulty wayfinding, yet can still learn their way if the environment is supportive of wayfinding. There is beginning evidence that colorful, familiar (easily identified), and personally meaningful cues placed at key decision points and residents' rooms can help individuals with AD find their way.
  • Article
    Full-text available
    Several studies have pointed out that egocentric and allocentric spatial impairments are one of the earliest manifestations of Alzheimer's Disease (AD). It is less clear how a break in the continuous interaction between these two representations may be a crucial marker to detect patients who are at risk to develop dementia. The main objective of this study is to compare the performances of participants suffering from amnestic mild cognitive impairment (aMCI group), patients with AD (AD group) and a control group (CG), using a virtual reality (VR)-based procedure for assessing the abilities in encoding, storing and syncing different spatial representations. In the first task, participants were required to indicate on a real map the position of the object they had memorized, while in the second task they were invited to retrieve its position from an empty version of the same virtual room, starting from a different position. The entire procedure was repeated across three different trials, depending on the object location in the encoding phase. Our finding showed that aMCI patients performed significantly more poorly in the third trial of the first task, showing a deficit in the ability to encode and store an allocentric viewpoint independent representation. On the other hand, AD patients performed significantly more poorly when compared to the CG in the second task, indicating a specific impairment in storing an allocentric viewpoint independent representation and then syncing it with the allocentric viewpoint dependent representation. Furthermore, data suggested that these impairments are not a product of generalized cognitive decline or of general decay in spatial abilities, but instead may reflect a selective deficit in the spatial organization Overall, these findings provide an initial insight into the cognitive underpinnings of amnestic impairment in aMCI and AD patient exploiting the potentiality of VR.
  • Article
    Introduction: Overlapping and evolving symptoms lead to ambiguity in the diagnosis of dementia. Visuospatial function relies on parietal lobe function, which may be affected in the early stages of Alzheimer's disease (AD). This review evaluates visuospatial dysfunction in patients with AD, frontotemporal dementia, dementia with Lewy bodies, and vascular dementia to determine the diagnostic and prognostic potential of visuospatial tasks in AD. Methods: A systematic search of studies (1960–2016) investigating visuospatial dysfunction in dementia was conducted. Results: Tests measuring construction, specifically Block Design and Clock Drawing Test, and visual memory, specifically Rey-Osterrieth Complex Figure recall and topographical tasks, show the greatest diagnostic potential in dementia. The Benton visual retention, Doors and People, and topographical memory tests show potential as prognostic markers. Discussion: Tests of visuospatial function demonstrate significant diagnostic and prognostic potential in dementia. Further studies with larger samples of pathologically confirmed cases are required to verify clinical utility.
  • Article
    Full-text available
    None of the previous studies on aging have tested the influence of action with respect to the degree of interaction with the environment (active or passive navigation) and the source of itinerary choice (self or externally imposed), on episodic memory encoding. The aim of this pilot study was to explore the influence of these factors on feature binding (the association between what, where and when) in episodic memory and on the subjective sense of remembering. Navigation in a virtual city was performed by 64 young and 64 older adults in one of four modes of exploration: (1) passive condition where participants were immersed as passengers of a virtual car (no interaction, no itinerary control), (2) itinerary control (the subject chose the itinerary, but did not drive the car), (3) low or (4) high navigation control (the subject just moved the car on rails or drove the car with a steering wheel and a gas pedal on a fixed itinerary, respectively). The task was to memorize as many events encountered in the virtual environment as possible along with their factual (what), spatial (where), and temporal (when) details, and then to perform immediate and delayed memory tests. An age related decline was evidenced for immediate and delayed feature binding. Compared to passive and high navigation conditions, and regardless of age groups, feature binding was enhanced by low navigation and itinerary control conditions. The subjective sense of remembering was boosted by the itinerary control in older adults. Memory performance following high navigation was specifically linked to variability in executive functions. The present findings suggest that the decision of the itinerary is beneficial to boost episodic memory in aging, although it does not eliminate age-related deficits. Active navigation can also enhance episodic memory when it is not too demanding for subjects' cognitive resources.
  • Article
    Objective: To evaluate whether visual cues are helpful for virtual spatial navigation and memory in Alzheimer's disease (AD) and patients with mild cognitive impairment (MCI). Method: 20 patients with AD, 18 patients with MCI and 20 age-matched healthy controls (HC) were included. Participants had to actively reproduce a path that included 5 intersections with one landmark at each intersection that they had seen previously during a learning phase. Three cueing conditions for navigation were offered: salient landmarks, directional arrows and a map. A path without additional visual stimuli served as control condition. Navigation time and number of trajectory mistakes were recorded. Results: With the presence of directional arrows, no significant difference was found between groups concerning the number of trajectory mistakes and navigation time. The number of trajectory mistakes did not differ significantly between patients with AD and patients with MCI on the path with arrows, the path with salient landmarks and the path with a map. There were significant correlations between the number of trajectory mistakes under the arrow condition and executive tests, and between the number of trajectory mistakes under the salient landmark condition and memory tests. Conclusion: Visual cueing such as directional arrows and salient landmarks appears helpful for spatial navigation and memory tasks in patients with AD and patients with MCI. This study opens new research avenues for neuro-rehabilitation, such as the use of augmented reality in real-life settings to support the navigational capabilities of patients with MCI and patients with AD. (PsycINFO Database Record
  • Article
    Full-text available
    The recent appearance of low cost virtual reality (VR) technologies-like the Oculus Rift, the HTC Vive and the Sony PlayStation VR-and Mixed Reality Interfaces (MRITF)-like the Hololens-is attracting the attention of users and researchers suggesting it may be the next largest stepping stone in technological innovation. However, the history of VR technology is longer than it may seem: the concept of VR was formulated in the 1960s and the first commercial VR tools appeared in the late 1980s. For this reason, during the last 20 years, 100s of researchers explored the processes, effects, and applications of this technology producing 1000s of scientific papers. What is the outcome of this significant research work? This paper wants to provide an answer to this question by exploring, using advanced scientometric techniques, the existing research corpus in the field. We collected all the existent articles about VR in the Web of Science Core Collection scientific database, and the resultant dataset contained 21,667 records for VR and 9,944 for augmented reality (AR). The bibliographic record contained various fields, such as author, title, abstract, country, and all the references (needed for the citation analysis). The network and cluster analysis of the literature showed a composite panorama characterized by changes and evolutions over the time. Indeed, whether until 5 years ago, the main publication media on VR concerned both conference proceeding and journals, more recently journals constitute the main medium of communication. Similarly, if at first computer science was the leading research field, nowadays clinical areas have increased, as well as the number of countries involved in VR research. The present work discusses the evolution and changes over the time of the use of VR in the main areas of application with an emphasis on the future expected VR's capacities, increases and challenges. We conclude considering the disruptive contribution that VR/AR/MRITF will be able to get in scientific fields, as well in human communication and interaction, as already happened with the advent of mobile phones by increasing the use and the development of scientific applications (e.g., in clinical areas) and by modifying the social communication and interaction among people.
  • Preprint
    BACKGROUND Traditional methods for assessing memory are expensive and have high administrative costs. Memory assessment is important for establishing cognitive impairment in cases such as detecting dementia in older adults. Technology can assist in better quality outcome in such crucial screening, by supporting the wellbeing of individuals and offering them an engaging, cognitively challenging task, that is not stressful. However, unmet user needs can compromise the validity of the outcome. Therefore, screening technology, particularly for older adults, must address their specific design and usability requirements. OBJECTIVE The objective of this research was to design and evaluate the feasibility of an immersive Virtual Reality (VR) platform to assess spatial navigation memory in older adults and establish its compatibility by comparing the outcome to a standard screening platform on computer PC. METHODS VR-CogAssess, is a platform integrating an Oculus Rift Head Mounted Display (HMD) and immersive photo-realistic imagery. In a pilot study with healthy older adults (N = 42, age M(SD) = 73.22(9.26)) a landmark recall test was conducted and assessment on the VR-CogAssess was compared against a Standard PC (SPC) setup. RESULTS Results showed participants in VR were more engaged (p = .003), achieved higher landmarks recall scores (p = .004), made less navigational mistakes (p = .042) and reported a higher level of presence (p = .002). CONCLUSIONS The study findings suggest immersive VR is feasible and compatible with SPC counterpart for spatial navigation memory assessment. The study provides a set of design guidelines for creating similar platforms in the future.
  • Article
    This research aims to reconsider and support the use of spatial tasks based on familiar geographical information in the neuropsychological assessment of topographical (dis)orientation. Performance on two spatial tasks based on familiar information —l andmark positioning on a map and map of Italy — were compared in two studies assessing allocentric orientation among young and healthy elderly with different levels of education (Study 1) and elderly with and without probable cognitive impairment (Study 2). Results from Study 1 showed that the map of Italy task was affected by education, while the landmark positioning on a map was not. Results of Study 2 showed that both tasks were sensitive to different levels of cognitive functioning in a sample of community-dwelling seniors. Overall, spatial tasks based on mental representation of the hometown environment may be an important supplement in the assessment of allocentric topographical disorientation, discriminating typical from atypical aging.
  • Article
    Full-text available
    We investigated age differences in memory for spatial routes that were either actively or passively encoded. A series of virtual environments were created and presented to 20 younger (Mean age = 19.71) and 20 older (Mean age = 74.55) adults, through a cardboard viewer. During encoding, participants explored routes presented within city, park, and mall virtual environments, and were later asked to re-trace their travelled routes. Critically, participants encoded half the virtual environments by passively viewing a guided tour along a pre-selected route, and half through active exploration with volitional control of their movements by using a button press on the viewer. During retrieval, participants were placed in the same starting location and asked to retrace the previously traveled route. We calculated the percentage overlap in the paths travelled at encoding and retrieval, as an indicator of spatial memory accuracy, and examined various measures indexing individual differences in their cognitive approach and visuo-spatial processing abilities. Results showed that active navigation, compared to passive viewing during encoding, resulted in a higher accuracy in spatial memory, with the magnitude of this memory enhancement being significantly larger in older than in younger adults. Regression analyses showed that age and score on the Hooper Visual Organizational test predicted spatial memory accuracy, following the passive and active encoding of routes. The model predicting accuracy following active encoding additionally included the distance of stops from an intersection as a significant predictor, illuminating a cognitive approach that specifically contributes to memory benefits in following active navigation. Results suggest that age-related deficits in spatial memory can be reduced by active encoding.
  • Article
    Full-text available
    In the field of spatial cognition research the mutual relationship between perception and action that brings out spatial orientation was lately investigated. Besides, the sameness between creating a cognitive map from the exploration of a not simulated environment, from the use of an allocentric (survey-like) sketched map, and from the interaction with egocentric (route-like) 3D virtual environments, is generally contrived. To understand if different embodied affordances could provide different knowledge organization during wayfinding through the use of distinct spatial simulations, the same group of 61 healthy subjects experienced both the classical version of the Money’s Road Map test (M-RMT) and a virtual reality version of the Road Map test (VR-RMT). The M-RMT requires a allocentric to egocentric right/left reasoning to explore a stylized city provided in a survey perspective. The VR-RMT is a 3D version of the same environment through which participants can actively navigate by choosing egocentric-based right/left directions in a route perspective. The results showed that the different embodiments afforded by the two environments and the increasing complexity in turn types provides different spatial outcomes. Results were discussed according to the sensorimotor coupling theory provided from the enactive cognition approach and significances for spatial cognition research were provided.
  • Article
    Background: Spatial navigation is a fundamental cognitive ability that allows an individual to maintain independence by facilitating the safe movement from one place to another. It emerges as one of the first deficits in patients with Alzheimer's disease (AD). Objective: To compare spatial navigation performance in the healthy elderly and AD patients through use of the Floor Maze Test (FMT) -an easy-to-apply two-dimensional (2D) maze -and determine which cognitive and functional capacities were associated with performance in this task. Methods: The FMT was administered to 24 AD patients and 36 healthy controls. Spatial navigation was evaluated through the FMT. Functional capacity was evaluated through the Senior Fitness Test battery of tests. Cognitive functions were evaluated through the Mini-Mental State Examination (MMSE), verbal fluency, digit span test, and the Rey Auditory Verbal Learning Test (RAVLT). Results: The group with AD was significantly slower and presented more errors at all stages of the FMT. Planning Time (PT) performance was associated with cardiorespiratory resistance (Step test) and delayed memory according to the RAVLT (R 2 =0.395, p<0.001). Performance in the Immediate Maze Time (IMT) and Delayed Maze Time (DMT) was associated with global cognitive status (MMSE) (R 2 =0.509) and delayed memory (R 2 =0.540). Conclusion: Patients with AD present significant spatial navigation deficits. Their performance on the FMT is influenced by cardiorespiratory capacity, memory, and global cognitive function. As exercise helps to improve executive function and functional capacity, future intervention studies should be carried out to analyze the possible effects of physical exercise on spatial navigation.
  • Article
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    Central nervous system diseases are not currently diagnosed based on knowledge of biological mechanisms underlying their symptoms. Greater understanding may be offered through an agnostic approach to traditional disease categories, where learning more about shared biological mechanisms across conditions could potentially reclassify sub-groups of patients to allow realisation of more effective treatments. This review represents the output of the collaborative group "PRISM", tasked with considering assay choices for assessment of attention and working memory in a transdiagnostic cohort of Alzheimer's disease and schizophrenia patients exhibiting symptomatic spectra of social withdrawal. A multidimensional analysis of this nature has not been previously attempted. Nominated assays (continuous performance test III, attention network test, digit symbol substitution, N-back, complex span, spatial navigation in a virtual environment) reflected a necessary compromise between the need for broad assessment of the neuropsychological constructs in question with several pragmatic criteria: patient burden, compatibility with neurophysiologic measures, availability of preclinical homologues.
  • Thesis
    Du fait de l'inefficacité des traitements actuellement disponibles pour le traitement de la maladie d'Alzheimer (MA), le développement de nouveaux traitements présente un enjeu majeur pour la communauté scientifique. De nombreuses cibles thérapeutiques sont actuellement à l'étude, comme les agonistes des récepteurs sérotoninergiques de type 4 (5-HT4R) qui non seulement ont démontré des actions antiamnésiantes dans différents modèles animaux, mais sont également capables d'augmenter la sécrétion d'acétylcholine et du neuropeptide protecteur sAPP alpha. La MA étant une pathologie multifactorielle, l'action sur une seule cible thérapeutique restera insuffisante pour son traitement, c'est pourquoi une nouvelle stratégie thérapeutique a émergé. Cette stratégie consiste à combiner des traitements symptomatiques comme les inhibiteurs de l'acetylcholinestérase (IAChE) et des traitements dits "disease modifier" afin d'agir en plus sur la composante physiopathologique de la maladie. En effet, la combinaison des IAChE et des agonistes des 5-HT4R a démontré des effets synergiques sur la mémoire chez les rongeurs. En lien avec ces résultats prometteurs a été développé le donecopride, un composé MTDL (Multi Target Directed Ligand : agit à la fois sur différentes cibles pharmacologiques) qui inhibe l'AChE et est agonistes des 5-HT4R. En effet, le donecopride présente des effets antiamnésiant et promnésiant chez les souris sauvages de souche NMRI et augmente la sécrétion de sAPP alpha. Ces premiers résultats prometteurs confirment la pertinence de cette approche MTDL et méritent d'être approfondis afin d'aboutir à de nouveaux traitements de la MA.
  • Article
    The aim of this study was to explore the acceptability, feasibility and usability of older people with mild dementia to use smartphone for wayfinding. Thirty cognitively normal older people and 16 people with mild dementia were recruited to participate in a wayfinding trial in the free-living environment. Five feasibility and three acceptability markers were compared between the groups. Content analysis on the video-recorded trial processes and individual interviews was employed to identify the usability issues. The results found that there were no significant between-group differences on the feasibility markers, except that the people with mild dementia needed significantly more time to complete the wayfinding trial and workshop; or on the acceptability items. Sensory/cognitive impairment and GPS signal reliability affected their usability. Mild dementia does not limit the older people to use smartphones for wayfinding in the free-living environment. Future studies should examine the efficacy and safety of smartphone to promote outdoor independence of the people with mild dementia.
  • Article
    Full-text available
    Impairments in spatial processing due to hippocampal degeneration have been observed in the years immediately preceding the diagnosis of Alzheimer's disease (AD) dementia. The demonstration of changes in spatial processing in preceding decades would provide a cognitive marker for pre-clinical AD and an outcome measure for early intervention trials. The present study examined allocentric and egocentric spatial processing in relation to future dementia risk in a middle-aged cohort. The CAIDE Dementia Risk Score (DRS) was calculated for 188 persons aged 40 to 59, of whom 94 had a parent with dementia. Participants underwent the Four Mountains Test (4MT) of allocentric spatial processing, the Virtual Reality Supermarket Trolley Task (VRSTT) of egocentric spatial processing, and 3T MRI scans. A significant negative association was found between the DRS and 4MT (Spearman correlation - 0.26, p = 0.0006), but not with the VRSTT. The 4MT was also found to be a better predictor of risk than tests of episodic memory, verbal fluency, or executive functioning. The results suggest that allocentric rather than egocentric processing may be a potential indicator of risk for late-onset AD, consistent with the hypothesis that the earliest cognitive changes in AD are driven by tau-related degeneration in the medial temporal lobe rather than amyloid-only deposition in the medial parietal lobe.
  • Article
    Orientation to time, date, and place is commonly utilized in clinical settings to aid in diagnosis, staging, and monitoring of Alzheimer's disease (AD). This study aimed to identify the cerebral metabolic correlates of orientation in patients with AD, and the degree to which regions associated with orientation overlap with memory-related structures. Eighty-five patients with a diagnosis of probable AD underwent fluorodeoxyglucose positron emission tomography (FDG-PET) and neuropsychological testing. Orientation items from the Dementia Rating Scale and recognition performance from the Consortium to Establish a Registry for AD (CERAD) Word List Learning test were correlated with cerebral glucose metabolism. Post-hoc analyses examined neuropsychological predictors of orientation. Better orientation performance related to greater cerebral metabolism in the bilateral middle-inferior temporal lobes, bilateral middle-posterior cingulate, left angular gyrus, and left middle occipital gyrus. In comparison, higher CERAD recognition discriminability score was associated with greater metabolic activity in left medial temporal lobe regions including the hippocampal and parahippocampal gyri, and the left fusiform gyrus. Post-hoc behavioral analyses revealed multiple cognitive functions to be related to orientation, including list learning, recognition memory, visuospatial functioning, attention, and language. Findings from the present study suggest that disorientation in AD results from dysfunction of a network of structures and cognitive abilities commonly found to be implicated in AD. The study supports the notion that memory is necessary but not sufficient for successful orientation.
  • Conference Paper
    The very long (VL) poly-T variant at rs10524523 ("523") of the TOMM40 gene may hasten the onset of late-onset Alzheimer's disease (LOAD) and induce more profound cognitive impairment compared with the short (S) poly-T variant. We examined the influence of TOMM40 "523" polymorphism on spatial navigation and its brain structural correlates. Participants were apolipoprotein E (APOE) ε3/ε3 homozygotes with amnestic mild cognitive impairment (aMCI). The homozygotes were chosen because APOE ε3/ε3 variant is considered "neutral" with respect to LOAD risk. The participants were stratified according to poly-T length polymorphisms at "523" into homozygous for S (S/S; n = 16), homozygous for VL (VL/VL; n = 15) TOMM40 poly-T variant, and heterozygous (S/VL; n = 28) groups. Neuropsychological examination and testing in real-space human analog of the Morris Water Maze were administered. Both self-centered (egocentric) and world-centered (allocentric) spatial navigation was assessed. Brain magnetic resonance imaging scans were analyzed using FreeSurfer software. The S/S group, although similar to S/VL and VL/VL groups in demographic and neuropsychological profiles, performed better on allocentric navigation (p ≤ 0.004) and allocentric delayed recall (p ≤ 0.014), but not on egocentric navigation. Both S/VL and VL/VL groups had thinner right entorhinal cortex (p ≤ 0.043) than the S/S group, whereas only the VL/VL group had thinner left entorhinal cortex (p = 0.043) and left posterior cingulate cortex (p = 0.024) than the S/S group. In conclusion, TOMM40 "523" VL variants are related to impairment in allocentric spatial navigation and reduced cortical thickness of specific brain regions among aMCI individuals with (LOAD neutral) APOE ε3/ε3 genotype. This may reflect a specific role of TOMM40 "523" in the pathogenesis of LOAD. Copyright © 2015 Elsevier Inc. All rights reserved.
  • Article
    Full-text available
    We provide a brief review and appraisal of recent and current virtual reality (VR) technology for Alzheimer’s disease (AD) applications. We categorize them according to their intended purpose (e.g., diagnosis, patient cognitive training, caregivers’ education, etc.), focus feature (e.g., spatial impairment, memory deficit, etc.), methodology employed (e.g., tasks, games, etc.), immersion level, and passive or active interaction. Critical assessment indicates that most of them do not yet take full advantage of virtual environments with high levels of immersion and interaction. Many still rely on conventional 2D graphic displays to create non-immersive or semi-immersive VR scenarios. Important improvements are needed to make VR a better and more versatile assessment and training tool for AD. The use of the latest display technologies available, such as emerging head-mounted displays and 3D smart TV technologies, together with realistic multi-sensorial interaction devices, and neuro-physiological feedback capacity, are some of the most beneficial improvements this mini-review suggests. Additionally, it would be desirable that such VR applications for AD be easily and affordably transferable to in-home and nursing home environments.
  • Article
    Topographical disorientation (TD) refers to navigational impairment as an effect of aging or brain damage. Decreases in navigational performance with aging are more due to deficits in the ability to mentally represent space in an object-centered (allocentric) than in a self-centered (egocentric) format. Familiarity/remoteness of spatial memory traces can represent a protective factor for TD in aging. Conversely, using newly learned information for assessment may lead to overestimating TD severity as it combines two contributing factors: heading (allocentric) disorientation and anterograde agnosia. A supplementary evaluation of TD with aging according to ecological spatial tasks is recommended. The core tasks should focus on landmark positioning, both on a blind map (allocentric) and along a route (egocentric) of the hometown so as to disentangle spatial memory for familiar/remote information from decline due to recent encoding of information.
  • Article
    Full-text available
    Background: Complexation was investigated as an approach to enhance the entrapment of the cationic neurotherapeutic drug, galantamine hydrobromide (GH) into cationic chitosan nanoparticles (CS-NPs) for Alzheimer's disease management intranasally. Biodegradable CS-NPs were selected due to their low production cost and simple preparation. The effects of complexation on CS-NPs physicochemical properties and uptake in rat brain were examined. Methods: Placebo CS-NPs were prepared by ionic gelation, and the parameters affecting their physicochemical properties were screened. The complex formed between GH and chitosan was detected by the FT-IR study. GH/chitosan complex nanoparticles (GH-CX-NPs) were prepared by ionic gelation, and characterized in terms of particle size, zeta potential, entrapment efficiency, in vitro release and stability for 4 and 25 °C for 3 months. Both placebo CS-NPs and GH-CX-NPs were visualized by transmission electron microscopy. Rhodamine-labeled GH-CX-NPs were prepared, administered to male Wistar rats intranasally, and their delivery to different brain regions was detected 1 h after administration using fluorescence microscopy and software-aided image processing. Results: Optimized placebo CS-NPs and GH-CX-NPs had a diameter 182 and 190 nm, and a zeta potential of +40.4 and +31.6 mV, respectively. GH encapsulation efficiency and loading capacity were 23.34 and 9.86%, respectively. GH/chitosan complexation prolonged GH release (58.07% ± 6.67 after 72 h), improved formulation stability at 4 °C in terms of drug leakage and particle size, and showed insignificant effects on the physicochemical properties of the optimized placebo CS-NPs (p > 0.05). Rhodamine-labeled GH-CX-NPs were detected in the olfactory bulb, hippocampus, orbitofrontal and parietal cortices. Conclusion: Complexation is a promising approach to enhance the entrapment of cationic GH into the CS-NPs. It has insignificant effect on the physicochemical properties of CS-NPs. GH-CX-NPs were successfully delivered to different brain regions shortly after intranasal administration suggesting their potential as a delivery system for Alzheimer's disease management.
  • Article
    Full-text available
    Alzheimer's disease (AD) is the most common cause of dementia and has become a severe public health issue. It is estimated that globally, 35.6% of people have some form of dementia. This number is expected to double by 2030, and possibly even triple by 2050. The disease is associated with deficits in cognition/memory and a reduced ability in coping with everyday life. Moreover, patients can experience behavioral alterations such as mood swings, depression and hallucinations. Therefore, it is common to find the presence of neuropsychiatric comorbidities such as depression, schizophrenia and bipolar disorder during the course or development of AD. These disorders can become severe enough to interfere with the patients daily functioning, and can worsen the course of the disease. However, little is known about the causal relationship between psychiatric comorbidities and AD, or the reasons for the predisposition of some individuals to such disorders. Therefore, the purpose of this review is to clarify the causal relationship between depression, schizophrenia and bipolar disorder with AD.
  • Article
    Full-text available
    The purpose of this review is to analyze the current knowledge about the higher, integrative level of the physiological system of orientation of animals in space. The significance of the study of this level caused by the fact that its disruption can cause deterioration of the capacity for spatial orientation (spatial agnosia) which is an important sign of some diseases of the brain, and in particular Alzheimer's disease. In recent decades, the main functional components of integration of information on space position of animals were discovered. The significance of these discoveries was reflected in a number of prestigious awards and honors, including the Nobel Prize in Physiology or Medicine for 2014.
  • Chapter
    An early decline in navigation abilities is one of the first sign of Alzheimer’s Disease (AD). More specifically, it has been suggested that allocentric impairments contribute significantly to this pathological decline. In this vein, the objective of the current work was to investigate the contribution of different spatial abilities involved in navigation (including allocentric ones) to the cognitive decline. Thirty elderly participated in the study, divided into two groups: Fifteen cognitively healthy aged individuals and fifteen individuals with AD. Our results showed that patients with AD performed significantly poorer in almost all tests evaluating spatial abilities in comparison to cognitively healthy aged individuals. Interestingly, we found that the allocentric abilities were the only significant predictor of the cognitive decline. Overall, these results suggested the primary role of allocentric impairments in contributing to the cognitive pathological decline.
  • Article
    Full-text available
    Spatial navigation is one of the cognitive functions known to decline in both normal and pathological aging. In the present study, we aimed to assess the neural correlates of the decline of topographical memory in patients with amnestic mild cognitive impairment (aMCI). Patients with aMCI and age-matched controls were engaged in an intensive learning paradigm, lasting for 5 days, during which they had to encode 1 path from an egocentric perspective and 1 path from an allocentric perspective. After the learning period, they were asked to retrieve each of these paths using an allocentric or egocentric frame of reference while undergoing a functional magnetic resonance imaging scan. We found that patients with aMCI showed a specific deficit in storing new topographical memories from an allocentric perspective and retrieving stored information to perform the egocentric task. Imaging data suggest that this general decline is correlated with hypoactivation of the brain areas generally involved in spatial navigation.
  • Article
    Significant progress has been made in characterizing the biological changes occurring in preclinical Alzheimer's disease (AD). Cognitive dysfunction has been viewed, however, as a late-stage phenomenon, despite increasing evidence that changes may be detected in the decades preceding dementia. In the absence of comprehensive evidence-based guidelines for preclinical cognitive assessment, longitudinal cohort and neuroimaging studies have been reviewed to determine the temporal order and brain biomarker correlates of specific cognitive functions. Episodic memory decline was observed to be the most salient cognitive function, correlating with Igh levels of amyloid deposition and hypoconnectivity across large-scale brain networks. Prospective studies point to early decline in both episodic and semantic memory processing as well as executive functions in the predementia period. The cognitive tests have, however, been principally those used to diagnose dementia. New procedures are required which target more finely the medial temporal lobe subregions first affected by clinically silent AD pathology.
  • Article
    The discovery of neuronal systems dedicated to computing spatial information, composed of functionally distinct cell types such as place and grid cells, combined with an extensive body of human-based behavioral and neuroimaging research has provided us with a detailed understanding of the brain's navigation circuit. In this review, we discuss emerging evidence from rodents, non-human primates, and humans that demonstrates how cognitive aging affects the navigational computations supported by these systems. Critically, we show 1) that navigational deficits cannot solely be explained by general deficits in learning and memory, 2) that there is no uniform decline across different navigational computations, and 3) that navigational deficits might be sensitive markers for impending pathological decline. Following an introduction to the mechanisms underlying spatial navigation and how they relate to general processes of learning and memory, the review discusses how aging affects the perception and integration of spatial information, the creation and storage of memory traces for spatial information, and the use of spatial information during navigational behavior. The closing section highlights the clinical potential of behavioral and neural markers of spatial navigation, with a particular emphasis on neurodegenerative disorders.
  • Article
    Experiencing an environment by navigating in it or reading a map (route and survey views, respectively) is a typical activity of everyday life. Previous research has demonstrated that aging coincides with a decline in spatial learning, but it is unclear whether this depends to some degree on how the learning conditions relate to the method used to assess the recall. The present study aims to shed light on this issue. Forty-six young, 43 young-old and 38 old-old adults learned outdoor environments from a map and a video, then performed sketch map and route repetition tasks. Participants were assessed on their visuo-spatial working memory (VSWM), and reported their self-assessed visuo-spatial inclinations. The results showed that young adults completed the sketch maps more accurately after learning from a map rather than a video. The same was true of the young-old participants (but not of the old-old), though their performance was not as good as the younger group’s. The learning condition had no effect on the route repetition task, however, and only age-related differences emerged, with both older groups performing less well than the young adults. After controlling for learning condition and age group, VSWM and participants’ reported propensity to explore places predicted their accuracy in both types of spatial task. The overall results, discussed in the light of spatial cognitive and aging models, show that learning condition (combined with recall tasks) and visuo-spatial factors influence spatial representations, even in aging.
  • Article
    Full-text available
    Abstract Spatial navigation is impaired in early stages of Alzheimer’s disease, and may be a defining behavioral marker of preclinical AD. A new rat model (TgF344-AD) of AD overcomes many limitations of other rodent models, though spatial navigation has not been comprehensively assessed. Using the hidden and cued platform variants of the Morris water task, a longitudinal assessment of spatial navigation was conducted on TgF344-AD (n = 16) and Fischer 344 (n = 12) male and female rats at three age ranges: 4 to 5 months, 7 to 8, and 10 to 11 months of age. TgF344-AD rats exhibited largely intact navigation at 4–5 months, with deficits in the hidden platform task emerging at 7–8 months and becoming significantly pronounced at 10–11 months of age. In general, TgF344-AD rats displayed less accurate swim trajectories to the platform and searched a wider area around the platform region compared to wildtype rats. Impaired navigation occurred in the absence of deficits in acquiring the procedural task demands or navigation to the cued platform location. Together, the results indicate that TgF344-AD rats exhibit comparable navigational deficits to those found in individuals with preclinical-AD.
  • Article
    The paper describes symptoms, pathogenesis and variants of topographic disorientation. The restorative and compensatory rehabilitation strategies in topographical disorientation are reviewed. It has been concluded that clarification of the variant of topographic disorientation and selection of optimal neurorehabilitation strategies is of great importance for improving medical and social outcomes in patients with stroke and other focal brain lesions.
  • Article
    Full-text available
    This review of the literature analyzes knowledge of the higher, integrative level of the physiological system by which animals orient themselves in space. Studies of the patterns of operation of the system at this level are relevant as impairments may underlie degradation of the ability to orient in space (spatial agnosia), an important sign of a number of brain diseases, particularly Alzheimer’s disease. Studies over recent decades have identified the main functional components of the system integrating information on an animal’s spatial position. The significance of these findings is reflected in a number of prestigious awards and honors, including the 2014 Nobel Prize in Physiology and Medicine.
  • Article
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    Background: Diagnosis of behavioral variant frontotemporal dementia (bvFTD) can be challenging, in particular when patients present with significant memory problems, which can increase the chance of a misdiagnosis of Alzheimer's disease (AD). Growing evidence suggests spatial orientation is a reliable cognitive marker able to differentiate these two clinical syndromes. Objective: Assess the integrity of egocentric and allocentric heading orientation and memory in bvFTD and AD, and their clinical implications. Method: A cohort of 22 patients with dementia (11 bvFTD; 11 AD) and 14 healthy controls were assessed on the virtual supermarket task of spatial orientation and a battery of standardized neuropsychological measures of visual and verbal memory performance. Results: Judgements of egocentric and allocentric heading direction were differentially impaired in bvFTD and AD, with AD performing significantly worse on egocentric heading judgements than bvFTD. Both patient cohorts, however, showed similar degree of impaired allocentric spatial representation, and associated hippocampal pathology. Conclusions: The findings suggest egocentric heading judgements offer a more sensitive discriminant of bvFTD and AD than allocentric map-based measures of spatial memory.
  • Article
    Full-text available
    In the field of spatial coding it is well established that we mentally represent objects for action not only relative to ourselves, egocentrically, but also relative to other objects (landmarks), allocentrically. Several factors facilitate allocentric coding, for example, when objects are task-relevant or constitute stable and reliable spatial configurations. What is unknown, however, is how object-semantics facilitate the formation of these spatial configurations and thus allocentric coding. Here we demonstrate that (i) we can quantify the semantic similarity of objects and that (ii) semantically similar objects can serve as a cluster of landmarks that are allocentrically coded. Participants arranged a set of objects based on their semantic similarity. These arrangements were then entered into a similarity analysis. Based on the results, we created two semantic classes of objects, natural and man-made, that we used in a virtual reality experiment. Participants were asked to perform memory-guided reaching movements toward the initial position of a target object in a scene while either semantically congruent or incongruent landmarks were shifted. We found that the reaching endpoints systematically deviated in the direction of landmark shift. Importantly, this effect was stronger for shifts of semantically congruent landmarks. Our findings suggest that object-semantics facilitate allocentric coding by creating stable spatial configurations.
Literature Review
  • Article
    Full-text available
    Background Many early-stage Alzheimer's disease (AD) patients suffer from spatial navigational impairment even in familiar environments. Growing evidence shows that the retrosplenial cortex (RSC) is more damaged in young-onset AD patients (YOAD, onset age before 65) than in late-onset AD (LOAD) in the early-stage of AD. Impaired translation between egocentric and allocentric representations of the environment, as a cause for spatial navigational impairment, usually occurs in people with lesions in the RSC. Objective To test translational ability between spatial representations in early-stage YOAD and LOAD patients. Methods Tests deemed sensitive to translation of spatial representations were used to evaluate 29 AD (14 YOAD, 15 LOAD) and 27 cognitively healthy controls (14 younger NC and 13 older NC). Results Younger NC outperformed YOAD in the tests of translation of spatial representations in spite of their equal basic visuoperceptual abilities and distance estimation. No such difference existed between LOAD and older NC. Conclusion The translation of egocentric-allocentric representation ability, as a principal function of RSC, does not deteriorate equally in early-stage AD patients of different onset age. That early-stage YOAD show more deviations in translation of their spatial representation ability deserves our attention because it may endanger their daily activities.
  • Article
    The neural basis of the amnesia characterizing early Alzheimer's disease (AD) remains uncertain. Postmortem pathological studies have suggested early involvement of the mesial temporal lobe, whereas in vivo metabolic studies have shown hypometabolism of the posterior cingulate cortex. Using a technique that combined the anatomic precision of magnetic resonance imaging with positron emission tomography, we found severe reductions of metabolism throughout a network of limbic structures (the hippocampal complex, medial thalamus, mamillary bodies, and posterior cingulate) in patients with mild AD. We then studied a cohort with mild cognitive impairment in whom amnesia was the only cognitive abnormality and found comparable hypometabolism through the same network. The AD and mild cognitive impairment groups were differentiated, however, by changes outside this network, the former showing significant hypometabolism in amygdala and temporoparietal and frontal association cortex, whereas the latter did not. The amnesia of very early AD reflects severe but localized limbic dysfunction.
  • Article
    Full-text available
    Systematic reviews and meta-analyses have become increasingly important in health care. Clinicians read them to keep up to date with their field [1],[2], and they are often used as a starting point for developing clinical practice guidelines. Granting agencies may require a systematic review to ensure there is justification for further research [3], and some health care journals are moving in this direction [4]. As with all research, the value of a systematic review depends on what was done, what was found, and the clarity of reporting. As with other publications, the reporting quality of systematic reviews varies, limiting readers' ability to assess the strengths and weaknesses of those reviews. Several early studies evaluated the quality of review reports. In 1987, Mulrow examined 50 review articles published in four leading medical journals in 1985 and 1986 and found that none met all eight explicit scientific criteria, such as a quality assessment of included studies [5]. In 1987, Sacks and colleagues [6] evaluated the adequacy of reporting of 83 meta-analyses on 23 characteristics in six domains. Reporting was generally poor; between one and 14 characteristics were adequately reported (mean = 7.7; standard deviation = 2.7). A 1996 update of this study found little improvement [7]. In 1996, to address the suboptimal reporting of meta-analyses, an international group developed a guidance called the QUOROM Statement (QUality Of Reporting Of Meta-analyses), which focused on the reporting of meta-analyses of randomized controlled trials [8]. In this article, we summarize a revision of these guidelines, renamed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), which have been updated to address several conceptual and practical advances in the science of systematic reviews (Box 1). Box 1: Conceptual Issues in the Evolution from QUOROM to PRISMA Completing a Systematic Review Is an Iterative Process The conduct of a systematic review depends heavily on the scope and quality of included studies: thus systematic reviewers may need to modify their original review protocol during its conduct. Any systematic review reporting guideline should recommend that such changes can be reported and explained without suggesting that they are inappropriate. The PRISMA Statement (Items 5, 11, 16, and 23) acknowledges this iterative process. Aside from Cochrane reviews, all of which should have a protocol, only about 10% of systematic reviewers report working from a protocol [22]. Without a protocol that is publicly accessible, it is difficult to judge between appropriate and inappropriate modifications.
  • Article
    Eighty-three brains obtained at autopsy from nondemented and demented individuals were examined for extracellular amyloid deposits and intraneuronal neurofibrillary changes. The distribution pattern and packing density of amyloid deposits turned out to be of limited significance for differentiation of neuropathological stages. Neurofibrillary changes occurred in the form of neuritic plaques, neurofibrillary tangles and neuropil threads. The distribution of neuritic plaques varied widely not only within architectonic units but also from one individual to another. Neurofibrillary tangles and neuropil threads, in contrast, exhibited a characteristic distribution pattern permitting the differentiation of six stages. The first two stages were characterized by an either mild or severe alteration of the transentorhinal layer Pre-alpha (transentorhinal stages I-II). The two forms of limbic stages (stages III-IV) were marked by a conspicuous affection of layer Pre-alpha in both transentorhinal region and proper entorhinal cortex. In addition, there was mild involvement of the first Ammon's horn sector. The hallmark of the two isocortical stages (stages V-VI) was the destruction of virtually all isocortical association areas. The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations.
  • Article
    Full-text available
    Objective: We report the case of a patient (M.S.) who, after a left brain damage in posteromedial areas, showed a deficit in determining the direction of any destination with respect to his current position or to external frames (heading disorientation). Given that spatial cognition includes a wide range of cooperating abilities, we deemed that M.S.'s spatial disorientation could be ascribed to specific alterations within this multicomponent system where landmarks and spatial frames of reference contribute to organize information for different purposes. Method: M.S. and 12 healthy elderly people (NCs) were submitted to an extensive neuropsychological assessment and to 2 ad hoc spatial tasks: (a) Object-Location Memory Task (what, where, and their binding); and (b) spatial memory task combining categorical (nonmetric)/coordinate (metric) relations with egocentric/allocentric frames of reference (in verbal and visuomotor conditions). Results: M.S.'s performance was compared with that of NCs by means of a modified t test to small control sample size. M.S. met difficulty in positional processing and binding but not in object recognition. M.S. showed a selective deficit in the coordinate component in verbal (combined with both egocentric and allocentric frames) and visuomotor (only with the egocentric frame) spatial judgment tasks. In contrast, the categorical component looked always preserved in both frames of reference. Conclusions: The left posteromedial brain areas contribute in combining and translating metric relations according to frames of reference and in using these representations to guide actions according to an egocentric perspective.
  • Article
    Full-text available
    Although the memory impairment is a hallmark of Alzheimer's disease (AD), AD has also been characterized by spatial disorientation, which is present from its early stages. Spatial disorientation in AD manifests itself in getting lost in familiar and unfamiliar places and have been characterized more specifically using spatial navigation tests in both real space and virtual environments as an impairment in multiple spatial abilities, including allocentric and egocentric navigation strategies, visuo-spatial perception, or selection of relevant information for successful navigation. Patients suffering mild cognitive impairment (MCI), who are at a high risk of development of dementia, show impairment in a subset of these abilities, mainly connected with allocentric and egocentric processing. While spatial disorientation in typical AD patients probably reflects neurodegenerative changes in medial and posterior temporal, parietal, and frontal lobes, and retrosplenial cortex, the impairment of spatial navigation in MCI seem to be connected mainly with the medial temporal and also parietal brain changes. In this review, we will summarize the signs of brain disease in most MCI and AD patients showing in various tasks of spatial memory and navigation.
  • Article
    Full-text available
    The current theories on episodic memory suggest a crucial role of spatial processing for an effective retrieval. For a successful episodic recall, the long-term allocentric scene has to be translated into an egocentric scene. Here, we argue that a crucial role for an episodic retrieval is played by a "mental frame syncing" between two kinds of allocentric representations. This neurocognitive process allows an effective retrieval of our past experiences by synchronizing the allocentric view-point independent representation with the allocentric view-point dependent representation. If the "mental frame syncing" stops, even momentarily, it is difficult to reconstruct a coherent spatial scaffold upon which to effectively retrieve our previous events within an egocentric perspective. This is what apparently happens in Alzheimer's disease: a break in the "mental frame syncing" between these two kinds of allocentric representations, underpinned by damage to the hippocampus, may contribute significantly to the early deficit in episodic memory.
  • Article
    The construct of mild cognitive impairment (MCI) has evolved over the past 10 years since the publication of the new MCI definition at the Key Symposium in 2003, but the core criteria have remained unchanged. The construct has been extensively used worldwide, both in clinical and in research settings, to define the grey area between intact cognitive functioning and clinical dementia. A rich set of data regarding occurrence, risk factors and progression of MCI has been generated. Discrepancies between studies can be mostly explained by differences in the operationalization of the criteria, differences in the setting where the criteria have been applied, selection of subjects and length of follow-up in longitudinal studies. Major controversial issues that remain to be further explored are algorithmic versus clinical classification, reliability of clinical judgment, temporal changes in cognitive performances and predictivity of putative biomarkers. Some suggestions to further develop the MCI construct include the tailoring of the clinical criteria to specific populations and to specific contexts. The addition of biomarkers to the clinical phenotypes is promising but requires deeper investigation. Translation of findings from the specialty clinic to the population setting, although challenging, will enhance uniformity of outcomes. More longitudinal population-based studies on cognitive ageing and MCI need to be performed to clarify all these issues.
  • Article
    Full-text available
    The ability to orient in space constitutes a main sign of cognitive impairment in Alzheimer's disease (AD). Presently, a peculiar aspect of topographical disorientation in AD linked with spatial reference frame congruence appears to have been only minimally investigated. We aim to study whether there is a decline in performing the allo- to egocentric translation of spatial knowledge during different types of wayfinding in AD patients. We introduced two virtual reality tasks, the VR-Maze and VR-Road Map tasks, in which we compared 26 AD and 26 healthy, elderly subjects. The results emphasize that there is a specific reduction in performing allo- to egocentric spatial tasks in AD, whereas this reduction is not as evident in equivalent allocentric spatial tasks. The data are consistent with the neurological results regarding the early degeneration of the hippocampus and retrosplenial cortex in AD, which underlies the ability to translate between these two reference frames.
  • Article
    Mixed dementia (MD), i.e., the coexistence of Alzheimer's disease (AD) and cerebrovascular disease (CVD), is a common dementia subtype. Few studies have attempted to establish the cognitive profiles of mild-moderate MD and compare it to the profiles of AD using a comprehensive neuropsychological test battery. We aimed to establish the neuropsychological profile of mild-moderate MD in relation to mild-moderate AD. Patients with consensus diagnoses of MD and AD of mild-moderate severity (Clinical Dementia Rating score of 1-2) were recruited from a memory clinic. Cognitive performance was measured by a formal neuropsychological battery covering domains of attention, language, verbal and visual memory, visuoconstruction, visuomotor speed and executive function. Cognitive domain scores are z-scores calculated using the mean and SDs of the AD group. ANCOVAs with age and education as covariates were employed to examine differences in mean score difference of cognitive domains and subtests between patients with MD and AD. 151 patients were recruited with the majority of AD (n=96, 63.6%) and a minority of MD (n=55, 36.4%). There were no significant differences in the demographic characteristics of patients with MD and AD. However, patients with MD were significantly more impaired than AD patients in global cognitive composite, attention and visuoconstruction (global cognitive composite: -0.32±0.98 vs 0±1, p=0.011; attention: -0.32±0.90 vs 0±1, p=0.013; visuoconstruction: -0.27±0.99 vs 0±1, p=0.024, respectively). The neuropsychological profile of patients with MD of mild-moderate severity is characterized by a poorer global performance, as well as attention and visuoconstruction than those with AD of mild-moderate severity.
  • Article
    Full-text available
    Several Virtual Reality (VR) applications for the understanding, assessment and treatment of mental health problems have been developed in the last 15 years. Typically, in VR the patient learns to manipulate problematic situations related to his/her problem. In fact, VR can be described as an advanced form of human–computer interface that is able to induce a feeling of ‘presence’ in the computer-generated world experienced by the user. This feature transforms VR in an ‘empowering environment’, a sheltered setting where patients can start to explore and act without feeling threatened. With such assurance, they can freely explore, experiment, feel, live out and experience feelings and/or thoughts. The paper presents the current state of clinical research in this area. Furthermore, the open source ‘NeuroVR’ system and its potential clinical applications are presented and discussed.
  • Article
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    If an instance of conscious experience of the seemingly objective world around us could be regarded as a newly formed event memory, much as an instance of mental imagery has the content of a retrieved event memory, and if, therefore, the stream of conscious experience could be seen as evidence for ongoing formation of event memories that are linked into episodic memory sequences, then unitary conscious experience could be defined as a symbolic representation of the pattern of hippocampal neuronal firing that encodes an event memory – a theoretical stance that may shed light into the mind-body and binding problems in consciousness research. Exceedingly detailed symbols that describe patterns of activity rapidly self-organizing, at each cycle of the θ rhythm, in the hippocampus are instances of unitary conscious experience that jointly constitute the stream of consciousness. Integrating object information (derived from the ventral visual stream and orbitofrontal cortex) with contextual emotional information (from the anterior insula) and spatial environmental information (from the dorsal visual stream), the hippocampus rapidly forms event codes that have the informational content of objects embedded in an emotional and spatiotemporally extending context. Event codes, formed in the CA3-dentate network for the purpose of their memorization, are not only contextualized but also allocentric representations, similarly to conscious experiences of events and objects situated in a seemingly objective and observer-independent framework of phenomenal space and time. Conscious perception is likely to be related to more fleeting and seemingly internal forms of conscious experience, such as autobiographical memory recall, mental imagery, including goal anticipation, and to other forms of externalized conscious experience, namely dreaming and hallucinations; and evidence pointing to an important contribution of the hippocampus to these conscious phenomena will be reviewed.
  • Article
    Background: Cognitive impairments, particularly memory problems, are a defining feature of the early stages of Alzheimer's disease (AD) and vascular dementia. Cognitive training and cognitive rehabilitation are specific interventional approaches designed to address difficulties with memory and other aspects of cognitive functioning. The present review is an update of previous versions of this review. Objectives: The main aim of the current review was to evaluate the effectiveness and impact of cognitive training and cognitive rehabilitation for people with mild Alzheimer's disease or vascular dementia in relation to important cognitive and non-cognitive outcomes for the person with dementia and the primary caregiver in the short, medium and long term. Search methods: The CDCIG Specialized Register, ALOIS, which contains records from MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS and many other clinical trial databases and grey literature sources, was most recently searched on 2 November 2012. Selection criteria: Randomised controlled trials (RCTs), published in English, comparing cognitive rehabilitation or cognitive training interventions with control conditions, and reporting relevant outcomes for the person with dementia and/or the family caregiver, were considered for inclusion. Data collection and analysis: Eleven RCTs reporting cognitive training interventions were included in the review. A large number of measures were used in the different studies, and meta-analysis could be conducted for 11 of the primary and secondary outcomes of interest. Several outcomes were not measured in any of the studies. The unit of analysis in the meta-analysis was the change from baseline score. Overall estimates of treatment effect were calculated using a fixed-effect model, and statistical heterogeneity was measured using a standard Chi(2) statistic. One RCT of cognitive rehabilitation was identified, allowing examination of effect sizes, but no meta-analysis could be conducted. Main results: Cognitive training was not associated with positive or negative effects in relation to any reported outcomes. The overall quality of the trials was low to moderate. The single RCT of cognitive rehabilitation found promising results in relation to a number of participant and caregiver outcomes, and was generally of high quality. Authors' conclusions: Available evidence regarding cognitive training remains limited, and the quality of the evidence needs to improve. However, there is still no indication of any significant benefit derived from cognitive training. Trial reports indicate that some gains resulting from intervention may not be captured adequately by available standardised outcome measures. The results of the single RCT of cognitive rehabilitation show promise but are preliminary in nature. Further, well-designed studies of cognitive training and cognitive rehabilitation are required to obtain more definitive evidence. Researchers should describe and classify their interventions appropriately using available terminology.
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    The neural basis of navigation by humans was investigated with functional neuroimaging of brain activity during navigation in a familiar, yet complex virtual reality town. Activation of the right hippocampus was strongly associated with knowing accurately where places were located and navigating accurately between them. Getting to those places quickly was strongly associated with activation of the right caudate nucleus. These two right-side brain structures function in the context of associated activity in right inferior parietal and bilateral medial parietal regions that support egocentric movement through the virtual town, and activity in other left-side regions (hippocampus, frontal cortex) probably involved in nonspatial aspects of navigation. These findings outline a network of brain areas that support navigation in humans and link the functions of these regions to physiological observations in other mammals.
  • Article
    Recent studies of the relationship between progression from mild cognitive impairment (MCI) to Alzheimer disease (AD) and APOE ε4-allele revealed inconsistent results. To estimate the risk posed by APOE ε4-allele for developing AD in MCI subjects using meta-analysis and identify possible sources of heterogeneity between studies, we reviewed longitudinal epidemiological studies of the presence of APOE ε4-allele on risk for progression to dementia in MCI subjects, and conducted meta-analyses of the results from these studies. Our study was derived from 315 positive-outcome events and 461 negative-outcome events from 8 prospective studies. The pooled RR was statistically significant (pooled RR = 2.09; 95 % CI, 1.52–2.88). The Q statistics indicated high heterogeneity across studies (Q = 14.21, p = 0.003). RR were significantly related to the ethnicity of the sample (z = 3.58, p = 0.024). No significant heterogeneity was observed after stratification in four European-population studies (χ 2 = 0.67, p = 0.880), but it remained in four American-population studies (χ 2 = 18.52, p = 0.003). Heterogeneity markedly reduced after excluding one specific study (Q = 4.9, p = 0.009; I 2 = 39 %). APOE ε4-allele conferred increased risk for progression to dementia in MCI subjects. Ethnicity is a critical factor to yield heterogeneity. Further studies using larger sample sizes are required.
  • Article
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    Virtual reality (VR) is an emerging technology with a variety of potential benefits for many aspects of rehabilitation assessment, treatment, and research. Through its capacity to allow the creation and control of dynamic 3-dimensional, ecologically valid stimulus environments within which behavioral responding can be recorded and measured, VR offers clinical assessment and rehabilitation options that are not available with traditional methods. Initial applications of VR in other aspects of medicine and psychology have yielded encouraging results, but continued research and understanding of this evolving technology will be crucial for its effective integration into rehabilitation. This article provides a brief introduction to VR technology, examines the specific benefits VR offers consumers and providers of rehabilitation services and discusses potential areas of application and important considerations in applying this technology. Finally, 2 examples of current Vr applications are presented. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
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    In the literature it is commonly reported that several spatial abilities decline with normal aging, even though such a decline is not uniform. So far, it is not yet clear which spatial components present a normal age-related decline, which ones are preserved and at what point the deficit is so severe to represent an index of mild cognitive impairment (MCI) or a symptom of potential degenerative progression as in the early-stage Alzheimer's disease (AD). In particular, AD (from early onset) is characterised by impairments in constructive abilities, visuospatial intelligence, spatial short-term memory deficits, and disorders of spatial orientation (topographical disorientation). MCI indicates a condition, generally affecting older individuals, characterized by cognitive deficits including memory and/or non memory impairments and at high risk of progression to dementia. Three MCI subgroups have been distinguished and a very high risk of developing AD is associated to the amnestic MCI subtypes. Further, recent studies have suggested that the allocentric component of spatial memory might be taken as predictor of AD from MCI. Given the frequency of visuospatial deficits in early-stage AD, evaluation of visuospatial processes is a promising approach to find predictive markers of AD. Here we report a review of the literature exploring specific visuospatial components in normal aging, MCI, and AD. In this way we could shed some light on the role of these components in the progression from MCI to AD and pave the way for future studies.
  • Article
    Given that the research area of cognitive intervention studies in the aging population is growing rapidly, it is important to review and gauge more recent intervention studies, in order to determine the evidence for the effectiveness of cognitive interventions. The purpose of the present review was to update the recent systematic reviews of Papp et al. (2009) and Martin et al. (2011), to evaluate the effectiveness of cognitive interventions in healthy older adults and people with MCI, by taking into account the methodological quality of the interventions studies. A systematic review of randomized controlled trials (RCT) and clinical studies published between August 2007 and February 2012 in Pubmed and PsychINFO was performed. The quality of the included RCTs was assessed according to the CONSORT criteria for RCTs. A total of thirty-five studies were included; twenty-seven RTCs and eight clinical studies. The content of the intervention studies differed widely, as did the methodological quality of the included RCTs, but was considerably low with an average of 44% of the Consort items included. The results show evidence that cognitive training can be effective in improving various aspects of objective cognitive functioning; memory performance, executive functioning, processing speed, attention, fluid intelligence, and subjective cognitive performance. However, the issue whether the effects of cognitive interventions generalize to improvement in everyday life activities is still unresolved and needs to be addressed more explicitly in future research.
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    In natural and virtual environments (VE) spatial learning depends on several factors including the spatial goal, environmental complexity and mode of learning. A factor influencing the mode of learning is the extent to which exploration is self-governed. The aim of this study was to investigate the effect of active (self-governed) vs. passive (avatar-guided) exploration on the organization of spatial knowledge of a large-scale VE in a wayfinding task. In particular, we wanted to test the hypothesis that self-governed explo-ration promotes the creation of a survey-type representation when participants are requested to explore efficiently (i.e. avoid repeatedly traversing the same paths). Twenty male participants were randomized to a passive group or an active group; both groups performed a two-phase task. In the first phase (learning phase), they learned an unfamiliar large-scale closed VE on two floors with a cross shaped ground plan. The pas-sive group learned by following an avatar; the active group explored at will. All were instructed to find, in the shortest possible time, target flags positioned through the VE. In the test phase, participants' spatial knowledge was assessed by three tasks: wayfinding (one session), pointing to the starting point of a traveled path (four sessions), and producing a sketch map of the VE. In the wayfinding task, 7 active participants found the way against 2 in the passive group. Among participants who found the way 5/7 in the active group have drawn a survey-type (hierarchically organized) map while none of the 2 in the passive group produced a map of this type. As expected, the groups did not differ in performance of the pointing tasks. These find-ings support the hypothesis that self-governed explorations in a VR are favored if spatial knowledge is organized in survey mode.
  • Article
    Normal aging and mild Alzheimer's disease (AD) are associated with declines in navigational skills, including allocentric and egocentric representations, cognitive mapping, landmark processing, and spatial memory. These changes, however, are associated with different patterns of structural and functional alterations in the neural network of navigation. In AD, these changes occur in the hippocampus, parahippocampal gyrus, parietal lobe, retrosplenial cortex, prefrontal cortex, and caudate nucleus, whereas in aging, modifications occur mainly in the prefrontal cortex and the hippocampus. The navigation abilities of patients with mild cognitive impairment (MCI) have been found to show different performance patterns, depending on their cognitive profiles. Since patients with MCI do not uniformly develop dementia of the Alzheimer type, it is important to identify reliable early cognitive markers of conversion to AD dementia. In this review, we propose that navigation deficits may help distinguish patients at higher risk of developing AD dementia from individuals with normal cognitive aging and those with other neurodegenerative diseases.
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    Spatial navigation is a skill of determining and maintaining a trajectory from one place to another. Mild progressive decline of spatial navigation develops gradually during the course of physiological ageing. Nevertheless, severe spatial navigation deficit can be the first sign of incipient Alzheimer's disease (AD), occurring in the stage of mild cognitive impairment (MCI), preceding the development of a full blown dementia. Patients with amnestic MCI, especially those with the hippocampal type of amnestic syndrome, are at very high risk of AD. These patients present with the same pattern of spatial navigation impairment as do the patients with mild AD. Spatial navigation testing of elderly as well as computer tests developed for routine clinical use thus represents a possibility for further investigation of this cognitive domain, but most of all, an opportunity for making early diagnosis of AD.
  • Article
    It has been recognized that molecular classifications will form the basis for neuropathological diagnostic work in the future. Consequently, in order to reach a diagnosis of Alzheimer's disease (AD), the presence of hyperphosphorylated tau (HP-tau) and β-amyloid protein in brain tissue must be unequivocal. In addition, the stepwise progression of pathology needs to be assessed. This paper deals exclusively with the regional assessment of AD-related HP-tau pathology. The objective was to provide straightforward instructions to aid in the assessment of AD-related immunohistochemically (IHC) detected HP-tau pathology and to test the concordance of assessments made by 25 independent evaluators. The assessment of progression in 7-µm-thick sections was based on assessment of IHC labeled HP-tau immunoreactive neuropil threads (NTs). Our results indicate that good agreement can be reached when the lesions are substantial, i.e., the lesions have reached isocortical structures (stage V–VI absolute agreement 91%), whereas when only mild subtle lesions were present the agreement was poorer (I–II absolute agreement 50%). Thus, in a research setting when the extent of lesions is mild, it is strongly recommended that the assessment of lesions should be carried out by at least two independent observers.
  • Article
    A virtual reality environment was used to test memory performance for simulated “real-world” spatial and episodic information in a 22-year-old male, Jon, who has selective bilateral hippocampal pathology caused by perinatal anoxia. He was allowed to explore a large-scale virtual reality town and was then tested on his memory for spatial layout and for episodes experienced. Topographical memory was tested by assessing his ability to navigate, recognize previously visited locations, and draw maps of the town. Episodic memory was assessed by testing the retrieval of simulated events which consisted of collecting objects from characters while following a route through the virtual town. Memory for the identity of objects, as well as for where they were collected, from whom, and in what order, was also tested. While the first task tapped simple recognition memory, the latter three tested memory for context. Jon was impaired on all topographical tasks and on his recall of the context-dependent questions. However, his recognition of objects from the virtual town, and of “topographical” scenes (as evaluated by standard neuropsychological tests), was not impaired. These findings are consistent with the view that the hippocampus is involved in navigation, recall of long term allocentric spatial information and context-dependent episodic memory, but not visual pattern matching. Hippocampus 2001;11:715–725. © 2001 Wiley-Liss, Inc.
  • Article
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    It is believed that in Alzheimer's disease (AD) some areas of the brain are particularly vulnerable to specific degenerative processes and that they could exhibit neuronal dysfunction in the earliest stage of the disease. The implications of the hippocampus in memory processes are very well known and it is likely that the hippocampus would be among the first areas of the brain affected by the pathogenic mechanisms occurring in AD. However, the distinction between the neurodegenerative changes that accompany normal ageing and those that characterize AD is not clear. Also, the distribution of the hippocampal cell loss in both normal aging and AD is not very well understood. In this context, we focused on the quantification of the neuronal density in the four specific areas of the hippocampus (CA1-CA4) of AD brains, as compared to an age-matched control group, by using the Nissl staining technique. We found a significant reduction of neuronal density especially in the CA1 and CA3 hippocampal areas. The most prominent decrease was found at the CA1 area level, as compared to all other 3 areas which were analyzed. In the present study we managed to demonstrate and confirm a significant neuronal loss of hippocampus in AD, as compared to an age-matched control group. Moreover, it seems that this decrease of hippocampal neuronal density is more prominent especially at the CA1 and also in the CA3 hippocampal areas. This could have important implications in the design of therapeutic and investigative strategies of AD. However, larger samples are necessary in order to provide the basis for firmer conclusions in this area of research.
  • Article
    Neuropsychological assessment has featured prominently over the past 30 years in the characterization of dementia associated with Alzheimer disease (AD). Clinical neuropsychological methods have identified the earliest, most definitive cognitive and behavioral symptoms of illness, contributing to the identification, staging, and tracking of disease. With increasing public awareness of dementia, disease detection has moved to earlier stages of illness, at a time when deficits are both behaviorally and pathologically selective. For reasons that are not well understood, early AD pathology frequently targets large-scale neuroanatomical networks for episodic memory before other networks that subserve language, attention, executive functions, and visuospatial abilities. This chapter reviews the pathognomonic neuropsychological features of AD dementia and how these differ from "normal," age-related cognitive decline and from other neurodegenerative diseases that cause dementia, including cortical Lewy body disease, frontotemporal lobar degeneration, and cerebrovascular disease.
  • Article
    Recent psychometric results [Mem. Cogn. 29 (2001) 745] have supported a distinction between mental abilities that require a spatial transformation of a perceived object (e.g., mental rotation) and those that involve imagining how a scene looks like from different viewpoints (e.g., perspective taking). Two experiments provide further evidence for and generalize this dissociation. Experiment 1 shows that the separability of mental rotation and perspective taking is not dependent on the method by which people are tested. Experiment 2 generalizes the distinction to account for perspective taking within perceived small-scale and imagined large-scale environments. Although dissociable, measures of perspective taking and mental rotation are quite highly correlated. The research suggests some reasons why psychometric studies have not found strong evidence for the separability of the spatial visualization and spatial orientation factors, although a strong dissociation between tasks that are dependent on mental rotation and perspective-taking processes has been found in the experimental cognitive literature.
  • Article
    In spatial cognition studies several cognitive factors were analysed in order to identify the aspect that could constitute the basis for the capacity of organising spatial knowledge into survey maps.This study presents a method for evaluating spatial ability, based on the capacity of obtaining a survey-type spatial knowledge organisation, in a recently explored virtual environment. The ability to plan optimal paths in virtual environments was examined in 40 female adult subjects. Spatial evaluation deriving from navigation of a simple virtual environment was compared with classical spatial survey tasks (wayfinding, pointing and sketch maps) performed after the active exploration of a complex virtual environment.Results show that there is a relationship between planning optimal paths and other spatial tasks related to survey representation.These findings highlight how the navigation-supported learning capacity results in a predictive factor for individuals’ assessment of spatial ability.
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    Alzheimer's disease (AD) in younger patients is associated with a higher prevalence of atypical symptoms. We examined neuropsychological performance according to age-at-onset. We assessed cognition in 172 patients with AD (81 early and 91 late onset) in five cognitive domains (memory, language, visuo-spatial functioning, executive functioning, attention). Dementia severity was assessed using the Mini-Mental State Examination (MMSE) and global cognitive decline using Cambridge Cognitive Examination (CAMCOG). Analyses of variance were performed with age-at-onset as between-subjects factor, and gender and education as covariates. Analysis was repeated after stratification for dementia severity (based on median MMSE). In early onset AD, age (mean ± SD) was 60 ± 4 years; 44 (54%) were female. In late onset AD, age was 72 ± 5 years; 47 (52%) were female. Dementia severity and global cognitive decline did not differ between groups (early onset: MMSE: 20 ± 5, CAMCOG: 69 ± 15, late onset: MMSE: 21 ± 5, CAMCOG: 70 ± 15; p > 0.05). Early onset patients performed worse than late onset patients on visuo-spatial functioning (p < 0.01), executive functioning (p < 0.001), and attention (p < 0.01). Late onset patients performed worse on memory, although not significantly (p = 0.11). Stratification for dementia severity showed that in mildly demented early onset patients, memory function was remarkably preserved compared to late onset patients (p < 0.01). In moderate AD, differences in memory function disappeared, but early onset patients performed worse on visuo-spatial functioning (p < 0.01), executive functioning (p < 0.001), and attention (p < 0.01) than late onset patients. Adjustment for APOE left results unchanged. In conclusion, early onset AD presents with a different cognitive profile and the disease course seems different. Relative sparing of memory function in early stages stresses the need to adequately test other cognitive domains.
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    Episodic memory impairment is a hallmark for early diagnosis of Alzheimer's disease. Most actual tests used to diagnose Alzheimer's disease do not assess the spatiotemporal properties of episodic memory and lead to false-positive or -negative diagnosis. We used a newly developed, nonverbal navigation test for Human, based on the objective experimental testing of a spatiotemporal experience, to differentially Alzheimer's disease at the mild stage (N = 16 patients) from frontotemporal lobar degeneration (N = 11 patients) and normal aging (N = 24 subjects). Comparing navigation parameters and standard neuropsychological tests, temporal order memory appeared to have the highest predictive power for mild Alzheimer's disease diagnosis versus frontotemporal lobar degeneration and normal aging. This test was also nonredundant with classical neuropsychological tests. As a conclusion, our results suggest that temporal order memory tested in a spatial navigation task may provide a selective behavioral marker of Alzheimer's disease.
  • Article
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    Cognitive deficits in older adults attributable to Alzheimer's disease (AD) pathology are featured early on by hippocampal impairment. Among these individuals, deterioration in spatial navigation, manifested by poor hippocampus-dependent allocentric navigation, may occur well before the clinical onset of dementia. Our aim was to determine whether allocentric spatial navigation impairment would be proportional to right hippocampal volume loss irrespective of general brain atrophy. We also contrasted the respective spatial navigation scores of the real-space human Morris water maze with its corresponding 2D computer version. We included 42 cognitively impaired patients with either amnestic mild cognitive impairment (n = 23) or mild and moderate AD (n = 19), and 14 cognitively intact older controls. All participants underwent 1.5T MRI brain scanning with subsequent automatic measurement of the total brain and hippocampal (right and left) volumes. Allocentric spatial navigation was tested in the real-space version of the human Morris water maze and in its corresponding computer version. Participants used two navigational cues to locate an invisible goal independent of the start position. We found that smaller right hippocampal volume was associated with poorer navigation performance in both the real-space (β = -0.62, P < 0.001) and virtual (β = -0.43, P = 0.026) versions, controlling for demographic variables, total brain and left hippocampal volumes. In subsequent analyses, the results were significant in cognitively impaired (P ≤ 0.05) but not in cognitively healthy (P > 0.59) subjects. The respective real-space and virtual scores strongly correlated with each other. Our findings indicate that the right hippocampus plays a critical role in allocentric navigation, particularly when cognitive impairment is present.
  • Article
    The clinical hallmark of Alzheimer's disease (AD) is a gradual decline in cognitive function. For the majority of patients the initial symptom is an impairment in episodic memory, i.e., the ability to learn and retain new information. This is followed by impairments in other cognitive domains (e.g., executive function, language, spatial ability). This impairment in episodic memory is evident among individuals with mild cognitive impairment (MCI) and can be used to predict likelihood of progression to dementia, particularly in association with AD biomarkers. Additionally, cognitively normal individuals who are likely to progress to mild impairment tend to perform more poorly on tests of episodic memory than do those who remain stable. This cognitive presentation is consistent with the pathology of AD, showing neuronal loss in medial temporal lobe structures essential for normal memory. Similarly, there are correlations between magnetic resonance imaging (MRI) measures of medial temporal lobe structures and memory performance among individuals with mild cognitive impairment. There are recent reports that amyloid accumulation may also be associated with memory performance in cognitively normal individuals.
  • Conference Paper
    The self-reference system architecture developed to explain the retrieval of spatial knowledge from long-term memory is reviewed and expanded to include navigational tracking as one of its operations. A distinction is made between the operation of the self-reference system at a perceptual-motor and a representational level, and a case is made that if a representational self-reference system is to function as a navigational tracking device, it must be closely connected with the perceptual-motor level. Existing empirical evidence is reviewed and new empirical evidence is reported that explores the connections between the two levels of functioning. Additionally, the operations that would enable a self-reference system to function as a tracking device are derived from an animal model of sense of direction. The ideas explored in this manuscript rely on the premise that spatial memory systems evolved in the service of spatial navigation.
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    Full-text available
    Although the literatures on human spatial cognition and animal navigation often make distinctions between egocentric and allocentric (also called exocentric or geocentric) representations, the terms have not generally been well defined. This chapter begins by making formal distinctions between three kinds of representations: allocentric locational, egocentric locational, and allocentric heading representations. These distinctions are made in the context of whole-body navigation (as contrasted, e.g., with manipulation). They are made on the basis of primitive parameters specified by each representation, and the representational distinctions are further supported by work on brain mechanisms used for animal navigation. From the assumptions about primitives, further inferences are made as to the kind of information each representation potentially makes available. Empirical studies of how well people compute primitive and derived spatial parameters are briefly reviewed. Finally, the chapter addresses what representations humans may use for processing spatial information during physical and imagined movement, and work on imagined updating of spatial position is used to constrain the connectivity among representations.
  • Article
    Spatial navigation performance in the Hidden Goal Task (HGT), a real-space human analogue of the Morris Water Maze, can identify amnestic mild cognitive impairment (aMCI) patients with memory impairment of the hippocampal type, a known indicator of incipient Alzheimer's disease (AD). Contrast results from computer versus real-space versions of the HGT. A total of 42 aMCI patients were clinically and neuropsychologically classified into: (1) memory impairment of the hippocampal type--the hippocampal aMCI (HaMCI; n = 10) and (2) isolated retrieval impairment--the nonhippocampal aMCI (NHaMCI; n = 32). Results were compared to the control (n = 28) and AD (n = 21) groups. The HaMCI group, although similar to the NHaMCI group with respect to overall cognitive impairment, performed poorer on the computer version of the HGT and yielded parallel results to the real-space version. The two versions were strongly correlated. Both versions of the HGT can reliably identify aMCI with pronounced memory impairment of the hippocampal type. The computer version of the HGT may be a useful, relatively inexpensive screening tool for early detection of individuals at a high risk of AD.
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    Virtual reality (VR) environments are increasingly being used by neuroscientists to simulate natural events and social interactions. VR creates interactive, multimodal sensory stimuli that offer unique advantages over other approaches to neuroscientific research and applications. VR's compatibility with imaging technologies such as functional MRI allows researchers to present multimodal stimuli with a high degree of ecological validity and control while recording changes in brain activity. Therapists, too, stand to gain from progress in VR technology, which provides a high degree of control over the therapeutic experience. Here we review the latest advances in VR technology and its applications in neuroscience research.
  • Article
    Clinical criteria for the diagnosis of Alzheimer's disease include insidious onset and progressive impairment of memory and other cognitive functions. There are no motor, sensory, or coordination deficits early in the disease. The diagnosis cannot be determined by laboratory tests. These tests are important primarily in identifying other possible causes of dementia that must be excluded before the diagnosis of Alzheimer's disease may be made with confidence. Neuropsychological tests provide confirmatory evidence of the diagnosis of dementia and help to assess the course and response to therapy. The criteria proposed are intended to serve as a guide for the diagnosis of probable, possible, and definite Alzheimer's disease; these criteria will be revised as more definitive information become available.
  • Article
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    The neural basis of navigation by humans was investigated with functional neuroimaging of brain activity during navigation in a familiar, yet complex virtual reality town. Activation of the right hippocampus was strongly associated with knowing accurately where places were located and navigating accurately between them. Getting to those places quickly was strongly associated with activation of the right caudate nucleus. These two right-side brain structures function in the context of associated activity in right inferior parietal and bilateral medial parietal regions that support egocentric movement through the virtual town, and activity in other left-side regions (hippocampus, frontal cortex) probably involved in nonspatial aspects of navigation. These findings outline a network of brain areas that support navigation in humans and link the functions of these regions to physiological observations in other mammals.