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Differentiation of mild cognitive impairment using an entorhinal cortex- based test of VR navigation

Howett, D; Castegnaro, A; Krzywicka, K; Hagman1, J; Marchment, D; HENSON, R; king, J; ... Rio, M; + view all (2019) Differentiation of mild cognitive impairment using an entorhinal cortex- based test of VR navigation. Brain , 142 (6) pp. 1751-1766. 10.1093/brain/awz116. Green open access

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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.

Type: Article
Title: Differentiation of mild cognitive impairment using an entorhinal cortex- based test of VR navigation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/brain/awz116
Publisher version: https://doi.org/10.1093/brain/awz116
Language: English
Additional information: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Alzheimer’s disease; mild cognitive impairment; entorhinal cortex; path integration; virtual reality
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences > Clinical, Edu and Hlth Psychology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences > Institute of Cognitive Neuroscience
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Electronic and Electrical Eng
URI: https://discovery.ucl.ac.uk/id/eprint/10072931
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