Impairment of Everyday Spatial Navigation Abilities in Mild Cognitive Impairment Is Weakly Associated with Reduced Grey Matter Volume in the Medial Part of the Entorhinal Cortex

Article type: Research Article

Authors: Hallab, Asma^a | Lange, Catharina^a | Apostolova, Ivayla^b | Özden, Cansu^b | Gonzalez-Escamilla, Gabriel^{c; d} | Klutmann, Susanne^b | Brenner, Winfried^a | Grothe, Michel J.^{c; e} | Buchert, Ralph^{b; *} | for the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany | [b] Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany | [c] German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Rostock, Germany | [d] Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany | [e] Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Correspondence: [*] Correspondence to: Ralph Buchert, Martinistr. 52, 20246 Hamburg, Germany. Tel.: +49 40 741054347; Fax: +49 40 741040265; [email protected]; ORCID ID 0000-0002-0945-0724.

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (https://www.loni.ucla.edu/ADNI). As such, the investigators within ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this paper. A complete listing of ADNI investigators can be found at: https://adni.loni.ucla.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

Abstract: Background:Research in rodents identified specific neuron populations encoding information for spatial navigation with particularly high density in the medial part of the entorhinal cortex (ERC), which may be homologous with Brodmann area 34 (BA34) in the human brain. Objective:The aim of this study was to test whether impaired spatial navigation frequently occurring in mild cognitive impairment (MCI) is specifically associated with neurodegeneration in BA34. Methods:The study included baseline data of MCI patients enrolled in the Alzheimer’s Disease Neuroimaging Initiative with high-resolution structural MRI, brain FDG PET, and complete visuospatial ability scores of the Everyday Cognition test (VS-ECog) within 30 days of PET. A standard mask of BA34 predefined in MNI space was mapped to individual native space to determine grey matter volume and metabolic activity in BA34 on MRI and on (partial volume corrected) FDG PET, respectively. The association of the VS-ECog sum score with grey matter volume and metabolic activity in BA34, APOE4 carrier status, age, education, and global cognition (ADAS-cog-13 score) was tested by linear regression. BA28, which constitutes the lateral part of the ERC, was used as control region. Results:The eligibility criteria led to inclusion of 379 MCI subjects. The VS-ECog sum score was negatively correlated with grey matter volume in BA34 (β= –0.229, p = 0.022) and age (β= –0.124, p = 0.036), and was positively correlated with ADAS-cog-13 (β= 0.175, p = 0.003). None of the other predictor variables contributed significantly. Conclusion:Impairment of spatial navigation in MCI is weakly associated with BA34 atrophy.

Keywords: Entorhinal cortex, ¹⁸F-fluorodeoxyglucose, grid cells, magnetic resonance imaging, mild cognitive impairment, positron emission tomography, spatial navigation, volumetry

DOI: 10.3233/JAD-200520

Journal: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 1149-1159, 2020