Using virtual reality to distinguish subjects with multiple‐ but not single‐
domain amnestic mild cognitive impairment from normal elderly subjects
Article in Psychogeriatrics · March 2018
DOI: 10.1111/psyg.12301
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ORIGINAL ARTICLE
Using virtual reality to distinguish subjects with multiple- but not single-domain amnestic mild cognitive impairment from normal elderly subjects
Alireza MOHAMMADI ,1Mahmoud KARGAR2and Ehsan HESAMI3
1Neuroscience Research Center, Baqiyatallah Uni- versity of Medical Sciences,2Department of Speech Therapy, School of Rehabilitation, Tehran Univer- sity of Medical Sciences and3Department of Speech Therapy, University of Social Welfare and Rehabili- tation Science, Tehran, Iran
Correspondence: Dr Alireza Mohammadi PhD, Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. P.O. Box 19395-6558, Tehran 1413643561, Email: ar.
Disclosure: The authors have no potential conflicts of interest to declare regarding this article.
Received 12 May 2017; revision received 19 July 2017;
accepted 26 July 2017.
Key words: allocentric memory, egocentric memory, mild cognitive impairment, spatial disorientation, virtual maze, virtual neighbourhood.
Abstract
Aim: Spatial disorientation is a hallmark of amnestic mild cognitive impair- ment (aMCI) and Alzheimer’s disease. Our aim was to use virtual reality to determine the allocentric and egocentric memory deficits of subjects with single-domain aMCI (aMCIsd) and multiple-domain aMCI (aMCImd). For this purpose, we introduced an advanced virtual reality navigation task (VRNT) to distinguish these deficits in mild Alzheimer’s disease (miAD), aMCIsd, and aMCImd.
Methods:The VRNT performance of 110 subjects, including 20 with miAD, 30 with pure aMCIsd, 30 with pure aMCImd, and 30 cognitively normal con- trols was compared. Our newly developed VRNT consists of a virtual neigh- bourhood (allocentric memory) and virtual maze (egocentric memory).
Verbal and visuospatial memory impairments were also examined with Rey Auditory-Verbal Learning Test and Rey-Osterrieth Complex Figure Test, respectively.
Results:We found that miAD and aMCImd subjects were impaired in both allocentric and egocentric memory, but aMCIsd subjects performed simi- larly to the normal controls on both tasks. The miAD, aMCImd, and aMCIsd subjects performed worse onfinding the target or required more time in the virtual environment than the aMCImd, aMCIsd, and normal controls, respec- tively. Ourfindings indicated the aMCImd and miAD subjects, as well as the aMCIsd subjects, were more impaired in egocentric orientation than allo- centric orientation.
Conclusion: We concluded that VRNT can distinguish aMCImd subjects, but not aMCIsd subjects, from normal elderly subjects. The VRNT, along with the Rey Auditory-Verbal Learning Test and Rey-Osterrieth Complex Figure Test, can be used as a valid diagnostic tool for properly distinguish- ing different forms of aMCI.
INTRODUCTION
Mild cognitive impairment (MCI) is the limited deterio- ration of cognitive abilities that is considered as a transitional phase for the onset of Alzheimer’s dis- ease (AD); it has a prevalence of 5.8–18.5% among the elderly population (50–95 years).1–3 Given the growing number of people with AD and the related
challenges, it is necessary to identify these AD patients as early as possible. As such, the diagnosis of this transitional phase as a clinical state between normal cognitive ageing and dementia can be impor- tant to preventing recurrence and progression to AD.4 MCI is categorized as amnestic (aMCI) or non- amnestic (naMCI) and, based on the affected areas,
as occurring in a single domain or multiple domains.
Memory impairment alone is defined as single- domain aMCI (aMCIsd), and memory loss plus other cognitive impairments is defined as multiple-domain aMCI (aMCImd). Similarly, naMCI is categorized as single domain or multiple domain.5–7
Although aMCI patients may have normal general cognitive functions and participate in activities of daily living, they are usually diagnosed based on objective memory complaints and subjective memory decline.3,8 Initial aMCI symptoms are often impaired memory encoding and retrieval of contextual memory. In par- ticular, persons with aMCI have problems remember- ing the relationship between objects or between an object and its context (associative memory).9The cog- nitive state of some of these patients appears to remain constant or even return to normal, but more than half progress to AD within 3–6 years.10–12
Working memory (WM), a central executive func- tion, is a type of short-term memory with a limited capacity; it is responsible for processing and manipu- lating information.13,14Although WM impairments are well known in AD,15–18 few studies have evaluated WM deficits in detail in individuals with aMCIsd and aMCImd. Patalong-Ogiewa et al. found that patients with MCI are impaired not only in WM but also in epi- sodic memory, suggesting that the defect is not lim- ited to the hippocampus.13 Additionally, magnetic resonance imaging (MRI)-based brain volumetric studies confirmed grey matter loss in the medial tem- poral, parietal, and frontal areas of patients with aMCI.19,20 Furthermore, individual performance dur- ing a navigation task was confidently associated with the grey matter volume of the dorsolateral prefrontal cortex and hippocampus.21–23 Extensive neuroimag- ing studies in adults showed that the dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, pre- motor cortex, and posterior parietal cortex have criti- cal roles in visuospatial working memory.24–27 Therefore, investigating spatial memory deficits in AD and MCI is important for understanding the patho- physiology of MCI and predicting dementia.1,28
Spatial disorientation is one of the early manifesta- tions of AD and MCI, and it may become a diagnostic marker for these diseases in the near future. This problem occurs when patients are in an unfamiliar place in the early stages of the disease, but it hap- pens even in a familiar environment in advanced stages.29,30Allocentric and egocentric references are
two main types of spatial navigation. Allocentrism (object- or environment-centred) refers to the ability to experience the world from a more impersonal view and more familiar environment; egocentrism (ego- or body-centred) refers to the ability to see the world from a personal view, which has a vital role in preser- ving a stable moment-to-moment perception.31,32 Studies on the neural basis of spatial navigation have indicated that the hippocampus and medial regions of the temporal lobe are involved in allocentric repre- sentations, whereas the parietal and striatal regions are important in egocentric processing.33,34
Some studies previously reported the spatial navi- gation deficits of MCI and AD patients21,35–37; these deficits are proportional to the right/left hippocampal volume.23,35Another report stressed the various diffi- culties in topographic memory38; it recalled the for- merly learned routes, landmarks, positions on the map, and visuospatial attention.29,39–41Wenigeret al.
designed a virtual reality task to identify egocentric and allocentric memory differences in aMCI and con- trol subjects. The task was superior to earlier tasks, but it did not assess the domains of the aMCI dis- ease (i.e. aMCIsd vs aMCImd) or distinguish them from AD.35,42 Similarly, reports from Kalová et al.,43 deIpolyi et al.,21 Cushmanet al.,41 Nedelska et al.,23 Marková et al.,37 and Laczóet al.did not classify the domains of the disease,44 but they did compare the performance of patients with MCI or aMCI with that of AD patients. In contrast, Hort et al. demonstrated the spatial navigation differences between AD, naMCI, aMCIsd, and aMCImd patients using the Hid- den Goal Task (HGT), which had been previously described by Stepankova.36,45
In this study, we aimed to compare the allocentric and egocentric spatial navigation abilities of miAD, aMCIsd, and aMCImd patients by investigating their impairments. Because conversion to AD is more common among aMCI patients (naMCI patients may develop into non-AD dementias)46 and the similarity in the performance between naMCI patients and healthy controls,36,44 we did not investigate naMCI.
Also, based on previous studies that had similar results from real and virtual spatial navigations,36,43,44 we did not assess navigation in the real environment.
Although HGT is a good task for evaluating allo- centric and egocentric memory deficits, our advanced virtual reality navigation task (VRNT) offers several advantages, including a three-dimensional
(3-D) and fully coloured environment and landmarks that are more realistic looking than those of the com- puter version of HGT. Moreover, HGT may be con- siderably simpler than our VRNT. As such, it seems that our VRNT is much more accurate than HGT in distinguishing the subtypes of MCI. In this regard, new virtual reality tools may be very useful in identify- ing spatial navigation and memory deficits.
Given that aMCIsd is an earlier stage of AD than aMCImd, we aimed to use virtual reality to detect aMCIsd as a pre-aMCImd phase from cognitively nor- mal controls (NC) and to prevent recurrence of the disease and development of miAD. For this purpose, we designed the VRNT with two virtual environments (virtual neighbourhood and virtual maze) to separate allocentric (virtual neighbourhood) and egocentric (vir- tual maze) spatial navigation. The virtual neighbour- hood was designed similarly to a real neighbourhood and included appropriate navigational landmarks to help subjects find their way. In contrast, there were no landmarks in the virtual maze, and subjects had to find the goal by recalling their route from memory. We also investigated whether there was a specific com- parative pattern of spatial navigation deficits among aMCIsd, aMCImd, and miAD patients.
METHODS Participants
A total of 110 subjects, including 20 with miAD, 30 with pure aMCIsd, 30 with pure aMCImd, and
30 cognitively normal controls (NC) with no evidence of cognitive impairment, were recruited from outpa- tient services at the Baqiyatallah Hospital (Tehran, Iran). Participants signed a standard informed con- sent approved by the local ethics committee. Sub- jects’data are presented in Table 1.
Patients with miAD were diagnosed based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. The diagnosis of aMCIsd and aMCImd were performed by an experi- enced neurologist according to Petersen and Negash and using the following criteria47: (i) the existence of any subjective memory complaint; (ii) normal orienta- tion and general cognitive performance according to Mini-Mental State Examination (MMSE) score (Persian version)48; (iii) normal score on language ability using Boston Naming Test; and (iv) no known causes of memory deficit (e.g. use of a medication known to affect memory performance, major medical or neurological illness).47 Inclusion criteria for NC were as follows: (i) no established subjective memory complaint; (ii) no approved recognizable cognitive and memory impairment; (iii) MMSE score≥27;
(iv) normal social functioning in the community; and (v) no active neurologic or psychiatric disease.49
Procedure
All subjects underwent neuropsychological assess- ment and completed a visuospatial navigation task using our recently developed VRNT. It took 12 months to administer the tests and evaluate all subjects.
Table 1 Demographic and neuropsychological characteristics of the groups
Characteristics NC (n= 30) miAD (n= 20) aMCImd (n= 30) aMCIsd (n= 30)
Age (years) 69.8671.432 73.652.476* 70.0671.638*** 70.0001.681***
MMSE 28.0671.014 19.31.031* 26.1670.912*,*** 27.0330.808*,***,*****
Education (years) 13.1332.725 11.252.51** 12.0332.326 12.9672.341
Right/left handedness (n) 30/0 20/0 30/0 30/0
Women/men (n) 15/15 13/7 19/11 18/12
Duration of disorder (years) — 4.050.825 1.70.651*** 2.10.712***
RAVLT
Total score 47.1331.074 18.151.814* 25.7331.436*,*** 32.41.773*,***,****
Immediate recall scores 10.1671.019 1.10.911* 2.70.749*,*** 4.8330.874*,***,****
Delayed recall scores 9.6670.994 0.550.759* 2.1670.746*,*** 4.0330.889*,***,****
R-OCFT
Immediate recall scores 10.0330.927 2.550.759* 4.4671.074*,*** 7.0330.808*,***,****
Delayed recall scores 9.5330.937 1.20.767* 3.3330.758*,*** 6.2330.773*,***,****
*P< 0.001 compared to the NC group.**P< 0.05 compared to the NC group.***P< 0.001 compared to the miAD group.****P< 0.001 compared to the aMCImd group.*****P< 0.003 compared to the aMCImd group. All comparisons made based onANOVAwith Tukey’s post-hoc test. Handedness is based on the Edinburgh Handedness Inventory. aMCImd, multiple-domain amnestic mild cognitive impairment; aMCIsd, single-domain amnestic mild cognitive impair- ment; miAD, mild Alzheimer’s disease; MMSE, Mini-Mental State Examination; NC, cognitively normal controls; R-OCFT, Rey-Osterrieth Complex Figure Test;
RAVLT, Rey Auditory-Verbal Learning Test. Values are meanSD.
Neuropsychological assessment
The neuropsychological assessment covered the fol- lowing cognitive domains: (i) verbal memory, as determined by the Rey Auditory-Verbal Learning Test (RAVLT) (i.e. the sum of five trials, recall after inter- vention, delayed recall after 30 min, and memory rec- ognition)50; (ii) non-verbal memory, as assessed by the Rey-Osterrieth Complex Figure Test (R-OCFT) immediate recall; (iii) visuospatial memory, as evalu- ated by R-OCFT 30-min delayed recall51; and (iv) overall cognitive function, as measured by the MMSE.48
Virtual reality environment task Test design
Computer-based virtual reality environments have already been described and used as tools for visuo- spatial memory assessment in previous studies.42,52 These virtual reality environments are colourful, tex- tured, and 3-D, and they also offer a first-person view. Actions in the environment can be controlled by individuals using a joystick.
Our advanced VRNT was designed with two virtual environments (virtual neighbourhood and virtual maze) to assess allocentric (virtual neighbourhood) and egocentric (virtual maze) spatial navigation. The virtual neighbourhood was modelled on the natural environment (i.e. a real neighbourhood) and included pertinent navigational landmarks to help subjectsfind their routes (Fig. 1). In contrast, the virtual maze did not contain any navigational landmarks so individuals had to find the goal by recalling their route from the memory (Fig. 2). Each of the virtual reality environ- ments (virtual neighbourhood and virtual maze) com- prised a 3-Dfirst-person view and a two-dimensional overhead view of the environment. First, the two- dimensional overhead view was shown to the sub- jects for 60 s, and then the 3-Dfirst-person view was presented. Subjects were then instructed to find the specified goal (i.e. parking in the virtual neighbour- hood; the ball in the virtual maze), which had been marked on the 2-D overhead view. All subjects had three trials to familiarize themselves with the task and five trials for their assessment. Reactions and response times were recorded.
Figure 1 The virtual neighbourhood. (a) First-person view. (b) Overhead view.
Figure 2 The virtual maze. (a) First-person view. (b) Overhead view.
The 3-Dfirst-person view of the virtual environment were produced using Photoshop CS6 (Adobe, Tehran, Tehran, Iran), AutoCAD (Autodesk, Tehran, Tehran, Iran), and 3ds Max (Autodesk) software and run in the Lumion 5.0 Pro editor (Tehran, Tehran, Iran). The size of overhead view and first-person view images were 1280×720 pixels and 1920×1080 pixels, respec- tively. Both the virtual neighbourhood and virtual maze were presented, and the number of correct and incor- rect responses and the completion time of each trial were recorded. The results were processed to pro- duce primary data tables for further statistical analysis.
Scoring
The number of correct responses and response time for each subject were calculated for all trials of the virtual neighbourhood and virtual maze. These were consid- ered the dependent variables in the statistical analysis.
Analysis
One-wayANOVA was used to evaluate the group differ- ences between normally distributed demographic and neuropsychological variables and the performance of miAD, aMCIsd, aMCImd, and NC on the VRNT (correct responses and response time). Tukey’s post-hoc method was applied for multiple comparisons of signif- icant effects between groups. Pearson’s correlation coefficient was used to determine the relationship between neuropsychological parameters and the vir- tual neighbourhood scores. All analyses were two- tailed, and the significance level was defined as P< 0.05. Statistical computations were carried out by the SPSS version 22 (IBM (International Business Machines Corporation), Tehran, Tehran, Iran.).
RESULTS
Descriptive statistics and neuropsychological scores
Demographic analysis showed significant differences between groups for age, MMSE score, duration of the disorder (P< 0.001), and years of education (P< 0.05). The subjects in the miAD, aMCIsd, and aMCImd groups were predominantly women (65%, 63%, and 60%, respectively), whereas the NC group had an equal number of men and women. More detailed demographic characteristics of the subjects are presented in Table 1.
Neuropsychological assessments indicated large between-group effects. On all tests, the miAD group had lower scores than the aMCIsd, aMCImd, and NC subjects (P< 0.001). Similarly, both MCI subtypes had lower scores than the NC group on all tests (P< 0.001), but aMCIsd subjects performed signifi- cantly better than the aMCImd subjects (P< 0.001).
Patients with miAD and aMCImd performed signifi- cantly worse on the RAVLT (total scores, immediate recall, and delayed recall) than the aMCIsd and NC subjects (P< 0.001). Compared with the NC sub- jects, the miAD, aMCIsd, and aMCImd subjects were more impaired according to all of the R-OCFT subt- ests (P< 0.001). Additionally, aMCImd subjects scored significantly lower on all subtests of R-OCFT than the aMCIsd subjects. These findings indicate that the classification of the groups was reflected in the results of neuropsychological tests. See Table 1 for more details about the neuropsychological fea- tures of the groups.
Virtual reality tasks: virtual neighbourhood and virtual maze
All subjects’ VRNT scores and response times for the five trials were analyzed using one-way ANOVA
test followed by Tukey’s post-hoc test. The results showed significant differences between groups in the virtual neighbourhood and virtual maze tasks (P< 0.001).
Virtual neighbourhood task
Comparisons of the scores among the miAD, aMCIsd, aMCImd, and NC subjects across the five trials showed significant differences on the virtual neighbourhood task (P< 0.001). Further analysis showed that miAD patients performed significantly worse than the NC and aMCI subjects on the virtual neighbourhood task (P< 0.001). Similarly, the results indicated that the aMCImd subjects were significantly more impaired than aMCIsd and NC subjects (P< 0.001), but they were less impaired than the miAD subjects (P< 0.001). Data indicated that the miAD subjects completed their trials in a longer time than the aMCI and NC subjects (P< 0.001), and the aMCImd subjects had a slower performance than the aMCIsd and NC subjects (P< 0.001) (Table 2).
Virtual maze task
Comparing the performance of all groups across the five virtual maze trials showed significant differences in the response scores (mean correct response, P< 0.001) and response times (P≤0. 002). Tukey’s post-hoc test revealed that miAD subjects performed worse than the NC and aMCI groups on the virtual maze task (P< 0.001). The response time analysis for all groups showed that miAD subjects required more time to complete the trials than the others (P< 0.001). Also, there was a significant difference between aMCIsd and aMCImd subjects (P< 0.001).
A comparison of aMCI and NC subjects indicated that there were no significant differences with regard response scores or response time (P> 0.05) (Table 2).
Relationship between neuropsychological variables and virtual neighbourhood performance
Pearson’s correlation coefficient was used to deter- mine the relationship between neuropsychological parameters and the virtual neighbourhood scores. The results showed a strong positive correlation between neuropsychological and virtual neighbourhood scores in all groups (P< 0.01). A strong negative correlation
was found between neuropsychological scores (RAVLT total scores, immediate recall, and delayed recall; R-OCFT immediate and delayed recall) and the mean response time for the virtual neighbourhood task (P< 0.01) (Table 3).
Relationship between neuropsychological variables and virtual maze performance
A strong positive relationship was seen between all neuropsychological scores and virtual maze scores (P< 0.001). However, the relationship between neu- ropsychological scores and the mean virtual maze response time showed a strong negative correlation in all groups (P< 0.001) (Table 3).
DISCUSSION
The primary aim of this study was to use virtual reality to compare the allocentric and egocentric memory of miAD, aMCIsd, aMCImd, and NC subjects. This inves- tigation revealed significant differences in the allo- centric and egocentric memory impairments among miAD and aMCI subtypes. The miAD and aMCImd subjects were impaired based on the results of the vir- tual neighbourhood (allocentric memory) and virtual maze (egocentric memory) tasks; the aMCIsd and NC
Table 2 Performance of groups on the VRNT (virtual neighbourhood, virtual maze)
Virtual reality task NC (n= 30) miAD (n= 20) aMCImd (n= 30) aMCIsd (n= 30)
Virtual neighbourhood
Mean correct response (5 trials) 4.3330.711 0.350.489* 2.10.994*,** 4.1330.507**,****
Mean response time (s) 77.5717.156 173.499.106* 136.43320.669*,** 83.3312.793**,****
Virtual maze
Mean correct response (5 trials) 4.0330.764 0.150.366* 10.787*,** 3.90.712**,****
Mean response time (s) 95.7817.971 178.024.854* 163.71312.824*,*** 100.51316.079**,****
*P< 0.001 compared to the NC group.**P< 0.001 compared to the miAD group.***P< 0.005 compared to the miAD group.****P< 0.001 compared to the aMCImd group. All comparisons made based onANOVAwith Tukey’s post-hoc test. aMCImd, multiple-domain amnestic mild cognitive impairment; aMCIsd, single-domain amnestic mild cognitive impairment; miAD, mild Alzheimer’s disease; NC, cognitively normal controls; VRNT, virtual reality navigation task.
Values are meanSD.
Table 3 Correlation between neuropsychological characteristics and the VRNT scores
Test Virtual neighbourhood
Mean response time of
virtual neighbourhood Virtual maze
Mean response time of virtual maze RAVLT
Five trials 0.830† −0.846† 0.784† −0.794†
Immediate recall 0.801† −0.822† 0.753† −0.761†
Delayed recall 0.733† −0.795† 0.725† −0.734†
R-OCFT
Immediate recall 0.885† −0.902† 0.847† −0.849†
Delayed recall 0.886† −0.904† 0.860† −0.864†
†Correlation is significant at the 0.01 level (two-tailed). R-OCFT, Rey-Osterrieth Complex Figure Test; RAVLT, Rey Auditory-Verbal Learning Test; VRNT, virtual reality navigation task. Values are meanSD.
groups performed similarly on both tasks. The aMCIsd and aMCImd groups performed significantly better on finding the target and required less time in the virtual environment than the aMCImd and miAD groups, respectively. Comparisons of the time spent to find the goal in the virtual maze and the virtual neighbour- hood showed that subjects needed more time to find the goal in the virtual maze than in the virtual neigh- bourhood. The miAD group spent the most timefind- ing the goal, whereas the NC group spent the least time. In addition, the aMCI subtypes had more diffi- cultyfinding their route in the virtual maze than in the virtual neighbourhood. In the other words, ourfindings indicated that the aMCIsd, aMCImd, and miAD sub- jects were more impaired in their egocentric than allo- centric orientation. The aMCIsd subjects did not perform as well as the NC subjects, but the difference was not significant either in allocentric or egocentric memory; this suggests that aMCIsd subjects cannot be distinguished from NC subjects via VRNT. How- ever, aMCIsd subjects performed significantly better than the aMCImd and miAD subjects and can be eas- ily distinguished from them.
In line with Hort et al.,36 who reported similarities in spatial navigation between aMCImd and miAD patients,36 we hypothesized that miAD and aMCImd subjects may be more impaired than aMCIsd sub- jects in the virtual neighbourhood and virtual maze.
This hypothesis was supported by our results: miAD and aMCImd subjects were impaired in both the vir- tual neighbourhood (allocentric memory) and virtual maze (egocentric memory) tasks, but aMCIsd sub- jects performed similarly to the NC subjects on both tasks. The differences between the aMCIsd and aMCImd groups were significant, but those between the aMCIsd and NC groups were not. Our findings also indicated that the miAD and aMCImd groups were more impaired than the others with regard to finding their way in the virtual environments; specifi- cally, they could not find landmarks and took a long time to reach the goal (parking in the virtual neigh- bourhood;finding the ball in the virtual maze).
Although only one previous study has addressed allocentric and egocentric memory deficits based on distinctions in aMCIsd and aMCImd,36 several stud- ies have examined these deficits among aMCI and AD subjects. Previous reports considered allocentric or/and egocentric navigation deficits in patients with MCI, aMCI (without single- or multiple-domain
classification), and early AD in real or virtual environ- ments.21,35,37,41,43,44,53
Kalová et al. reported that subjects with early-stage AD were severely impaired only in allocentric navigation and were able to remember several locations, but patients with subjec- tive memory problems showed no impairment.43 Kalová et al. used HGT for the first time, and their results were similar in both real and computer ver- sions.43 A case study, Burgesset al. reported a dis- tinct allocentric spatial memory deficit in a patient with very early AD.53 deIpolyi et al. and Cushman et al. reported that patients with mild and/or early- stage AD or MCI were impaired in recalling previously learned routes and landmarks; however, neither study classified the domains of the MCI patients or distin- guished between egocentric and allocentric navigation.21,41
In another study, Laczó et al. demonstrated that hippocampal aMCI subjects were more impaired than non-hippocampal aMCI subjects in spatial naviga- tion, but they did not categorize subjects as having aMCIsd or aMCImd.44 Likewise, Wenigeret al. com- pared the egocentric and allocentric memory deficits of 29 patients with aMCI (without domain categoriza- tion) with 29 healthy matched controls using a virtual reality environment (similar to our VRNT) that was superior to previously designed tasks.35 They reported allocentric and egocentric spatial navigation deficits, in addition to reduced right/left hippocampal volumes, in aMCI patients relative to cognitively healthy controls.35Hortet al.found that patients with aMCImd and AD were impaired in both allocentric and egocentric navigation compared to healthy con- trols, whereas aMCIsd patients were impaired only in the allocentric navigation.36 Also, Hort et al.reported that aMCIsd group performed 1.5-fold worse than the control group.36
In line with the report by Hort et al., our results showed that the miAD and aMCImd subjects were impaired in both allocentric (virtual neighbourhood) and egocentric (virtual maze) navigation, but the aMCImd subjects performed significantly better than miAD subjects. Unlike that report, we did notfind that aMCIsd subjects had significantly impaired allo- centric navigation; in fact, we found that the aMCIsd group performed similarly to the NC group in allo- centric and egocentric navigation. Our findings indi- cated that the aMCIsd subjects, as well as the aMCImd and miAD subjects, were more impaired in
egocentric than allocentric orientation (Table 2), sug- gesting that egocentric memory may be a potential biomarker (along with other neuropsychological assessments) to identify these patients. These valua- ble results may be thanks to the accuracy and com- prehensiveness of our newly developed VRNT.
We also explored the performance of the miAD, aMCIsd, and aMCImd subjects on the RAVLT and compared them with those of NC subjects. The results showed that miAD, aMCImd, and aMCIsd subjects performed worse on the RAVLT than the aMCImd, aMCIsd, and NC subjects, respectively.
Unlike on the VRNT, aMCIsd subjects performed sig- nificantly worse than NC subjects on the RAVLT, suggesting that the RAVLT can be used as a subsidi- ary psychological task to distinguish MCI subtype from normal elderly subjects.
Auditory-verbal memory is routinely assessed by RAVLT in MCI and AD patients, and their perfor- mance is compared with healthy subjects. It has been shown that the RAVLT subtests are reliable tools for distinguishing old-old individuals from AD patients. Furthermore, performance on the RAVLT delayed recall can differentiate individuals in the prodromal phase of AD and MCI from each other and from the healthy individuals.54,55 Similarly, Tierney et al. demonstrated that the RAVLT delayed recall can help predict probable AD with a high degree of accuracy.56 Our study also revealed that delayed recall contributes to the early detection of miAD patients and the differentiation of aMCI subtypes from cognitively normal subjects. Our findings con- firmed that the RAVLT can help predict probable aMCI, and we suggest that this test be used in the early assessment of individuals with subjective mem- ory complaints.
In this study, we analyzed the relationship between performance on the RAVLT subtests and on the VRNT. Our analysis showed that there is a strong positive relationship between the RAVLT total score, immediate recall, and delayed recall and the number of correct responses in the virtual neighbourhood and the virtual maze. A strong negative relationship was observed between the performances on the RAVLT subtests and the spent time tofind the given goal in the both virtual neighbourhood and the virtual maze.
Several studies have reported a reduction in the volume of the hippocampus and some brain regions,
such as parahippocampal and cingulate cortex, in patients with AD and MCI.35,57–62It was reported that performance on a virtual navigation task is confi- dently associated with the grey matter volume of the hippocampus and that MCI subjects with hippocam- pal memory impairment have many problems in either allocentric or egocentric navigation.22,44,63,64
Also, the allocentric navigation performance of aMCI and AD patients has been associated with the grey matter volume of the dorsolateral prefrontal cortex and right hippocampus.21,23 It is believed that the posterior hippocampus and posterior parietal cortex are brain regions that degenerate during the early stages of AD.65–67 Correct route learning and spatial abilities in MCI and AD patients are positively corre- lated with the volumes of these regions.21 A recent functional MRI study showed that the bilateral activity of the most posterior medial temporal lobe, precu- neus, postcentral gyrus, and retrosplenial cortex (noticeable on the right side) increased while sub- jected learned the virtual maze.68 Therefore, analyz- ing spatial disorientation (allocentric and egocentric navigation deficits), RAVLT scores, and functional MRI scans of the hippocampus, posterior parietal cortex, precuneus, postcentral gyrus, and retrosple- nial cortex can useful in determining a specific pat- tern that identifies aMCIsd, aMCImd, and miAD and preventing aMCIsd from developing into aMCImd and subsequently miAD.
We concluded that miAD and aMCImd subjects demonstrated impaired egocentric, allocentric, visual, and verbal memory in performing the VRNT tasks, but their allocentric memory was better than their egocentric memory (Table 4). The current study documented important differences between the per- formance of miAD, aMCIsd, aMCImd, and NC sub- jects based on VRNT and RAVLT. These findings suggest that aMCImd patients, but not aMCIsd patients, are detectable from normal elderly subjects by VRNT; this test, along with the RAVLT and R- OCFT, can be used as a valid neuropsychological biomarker to properly distinguish these patients from each other. Ultimately, simultaneous use of functional MRI, VRNT, RAVLT, and other diagnostic techniques may be very useful in obtaining an accurate diagnosis.
The main limitation of the present study was the low number of aMCIsd and aMCImd subjects and the difficulty infinding them. The second limitation of
this study was the unwillingness of some subjects to simultaneously perform the VRNT and complete the RAVLT and R-OCFT with MRI during the second phase of this project.
ACKNOWLEDGMENTS
This research was supported by a grant from the Neuroscience Research Center, Baqiyatallah Univer- sity of Medical Sciences (grant no. BMSU/950896).
We thank the subjects who participated in this study.
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Table 4 Spatial disorientation and visual/verbal memory deficits in the aMCIsd, aMCImd, and miAD patients
Patients Allocentric Egocentric Verbal memory Visual memory
miAD Impaired†,‡,§ Impaired†,‡,§ Impaired†,‡,§ Impaired†,‡,§ Lowest performance among all
subjects
Lowest performance among all subjects
Worst performance among subjects
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Getting lost and confused in navigation
Getting lost (too often) and confused in navigation
Lower than other groups Lower than other groups Better than egocentric navigation Worse than allocentric
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Better performance than miAD, but worse than aMCIsd and NC subjects
Better performance than miAD, but worse than aMCIsd and NC subjects
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