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Differentiation of mild cognitive impairment using an entorhinal cortex-based test of virtual reality navigation.

ABSTRACT: The entorhinal cortex is one of the first regions to exhibit neurodegeneration in Alzheimer's disease, and as such identification of entorhinal cortex dysfunction may aid detection of the disease in its earliest stages. Extensive evidence demonstrates that the entorhinal cortex is critically implicated in navigation underpinned by the firing of spatially modulated neurons. This study tested the hypothesis that entorhinal-based navigation is impaired in pre-dementia Alzheimer's disease. Forty-five patients with mild cognitive impairment (26 with CSF Alzheimer's disease biomarker data: 12 biomarker-positive and 14 biomarker-negative) and 41 healthy control participants undertook an immersive virtual reality path integration test, as a measure of entorhinal-based navigation. Behavioural performance was correlated with MRI measures of entorhinal cortex volume, and the classification accuracy of the path integration task was compared with a battery of cognitive tests considered sensitive and specific for early Alzheimer's disease. Biomarker-positive patients exhibited larger errors in the navigation task than biomarker-negative patients, whose performance did not significantly differ from controls participants. Path-integration performance correlated with Alzheimer's disease molecular pathology, with levels of CSF amyloid-β and total tau contributing independently to distance error. Path integration errors were negatively correlated with the volumes of the total entorhinal cortex and of its posteromedial subdivision. The path integration task demonstrated higher diagnostic sensitivity and specificity for differentiating biomarker positive versus negative patients (area under the curve = 0.90) than was achieved by the best of the cognitive tests (area under the curve = 0.57). This study demonstrates that an entorhinal cortex-based virtual reality navigation task can differentiate patients with mild cognitive impairment at low and high risk of developing dementia, with classification accuracy superior to reference cognitive tests considered to be highly sensitive to early Alzheimer's disease. This study provides evidence that navigation tasks may aid early diagnosis of Alzheimer's disease, and the basis of this in animal cellular and behavioural studies provides the opportunity to answer the unmet need for translatable outcome measures for comparing treatment effect across preclinical and clinical trial phases of future anti-Alzheimer's drugs.

SUBMITTER: Howett D

PROVIDER: S-EPMC6536917 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCognitive training using virtual reality (VR) may result in motivational and playful training for patients with mild cognitive impairment and mild dementia. Fully immersive VR sets patients free from external interference and thus encourages patients with cognitive impairment to maintain selective attention. The enriched environment, which refers to a rich and stimulating environment, has a positive effect on cognitive function and mood.ObjectiveThe aim of this study was to investigate the feasibility and usability of cognitive training using fully immersive VR programs in enriched environments with physiatrists, occupational therapists (OTs), and patients with mild cognitive impairment and mild dementia.MethodsThe VR interface system consisted of a commercialized head-mounted display and a custom-made hand motion tracking module. We developed the virtual harvest and cook programs in enriched environments representing rural scenery. Physiatrists, OTs, and patients with mild cognitive impairment and mild dementia received 30 minutes of VR training to evaluate the feasibility and usability of the test for cognitive training. At the end of the test, the usability and feasibility were assessed by a self-report questionnaire based on a 7-point Likert-type scale. Response time and finger tapping were measured in patients before and after the test.ResultsParticipants included 10 physiatrists, 6 OTs, and 11 patients with mild cognitive impairment and mild dementia. The mean scores for overall satisfaction with the program were 5.75 (SD 1.00) for rehabilitation specialists and 5.64 (SD 1.43) for patients. The response time of the dominant hand in patients decreased after the single session of cognitive training using VR, but this was not statistically significant (P=.25). There was no significant change in finger tapping in either the right or left hand (P=.48 and P=.42, respectively). None of the participants reported headaches, dizziness, or any other motion sickness after the test.ConclusionsA fully immersive VR cognitive training program may be feasible and usable in patients with mild cognitive impairment and mild dementia based on the positive satisfaction and willingness to use the program reported by physiatrists, OTs, and patients. Although not statistically significant, decreased response time without a change in finger tapping rate may reflect a temporary increase in attention after the test. Additional clinical trials are needed to investigate the effect on cognitive function, mood, and physical outcomes.

Project description:BackgroundTherapeutic virtual reality (VR) has emerged as an effective treatment modality for cognitive and physical training in people with mild cognitive impairment (MCI). However, to replace existing nonpharmaceutical treatment training protocols, VR platforms need significant improvement if they are to appeal to older people with symptoms of cognitive decline and meet their specific needs.ObjectiveThis study aims to design and test the acceptability, usability, and tolerability of an immersive VR platform that allows older people with MCI symptoms to simultaneously practice physical and cognitive skills on a dual task.MethodsOn the basis of interviews with 20 older people with MCI symptoms (15 females; mean age 76.25, SD 5.03 years) and inputs from their health care providers (formative study VR1), an interdisciplinary group of experts developed a VR system called VRADA (VR Exercise App for Dementia and Alzheimer's Patients). Using an identical training protocol, the VRADA system was first tested with a group of 30 university students (16 females; mean age 20.86, SD 1.17 years) and then with 27 older people (19 females; mean age 73.22, SD 9.26 years) who had been diagnosed with MCI (feasibility studies VR2a and VR2b). Those in the latter group attended two Hellenic Association Day Care Centers for Alzheimer's Disease and Related Disorders. Participants in both groups were asked to perform a dual task training protocol that combined physical and cognitive exercises in two different training conditions. In condition A, participants performed a cycling task in a lab environment while being asked by the researcher to perform oral math calculations (single-digit additions and subtractions). In condition B, participants performed a cycling task in the virtual environment while performing calculations that appeared within the VR app. Participants in both groups were assessed in the same way; this included questionnaires and semistructured interviews immediately after the experiment to capture perceptions of acceptability, usability, and tolerability, and to determine which of the two training conditions each participant preferred.ResultsParticipants in both groups showed a significant preference for the VR condition (students: mean 0.66, SD 0.41, t29=8.74, P<.001; patients with MCI: mean 0.72, SD 0.51, t26=7.36, P<.001), as well as high acceptance scores for intended future use, attitude toward VR training, and enjoyment. System usability scale scores (82.66 for the students and 77.96 for the older group) were well above the acceptability threshold (75/100). The perceived adverse effects were minimal, indicating a satisfactory tolerability.ConclusionsThe findings suggest that VRADA is an acceptable, usable, and tolerable system for physical and cognitive training of older people with MCI and university students. Randomized controlled trial studies are needed to assess the efﬁcacy of VRADA as a tool to promote physical and cognitive health in patients with MCI.

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Differentiation of mild cognitive impairment using an entorhinal cortex-based test of virtual reality navigation.

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