Spatial Pattern Separation Testing Differentiates Alzheimer's Disease Biomarker-Positive and Biomarker-Negative Older Adults With Amnestic Mild Cognitive Impairment

Martina Laczó; Ondrej Lerch; Lukas Martinkovic; Jana Kalinova; Hana Markova; Martin Vyhnalek; Jakub Hort; Jan Laczó

doi:10.3389/fnagi.2021.774600

Spatial Pattern Separation Testing Differentiates Alzheimer's Disease Biomarker-Positive and Biomarker-Negative Older Adults With Amnestic Mild Cognitive Impairment

Front Aging Neurosci. 2021 Nov 26:13:774600. doi: 10.3389/fnagi.2021.774600. eCollection 2021.

Authors

Martina Laczó^{1

2}, Ondrej Lerch^{1

2}, Lukas Martinkovic¹, Jana Kalinova¹, Hana Markova^{1

2}, Martin Vyhnalek^{1

2}, Jakub Hort^{1

2}, Jan Laczó^{1

2}

Affiliations

¹ Memory Clinic, Department of Neurology, Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czechia.
² International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czechia.

Abstract

Background: The hippocampus, entorhinal cortex (EC), and basal forebrain (BF) are among the earliest regions affected by Alzheimer's disease (AD) pathology. They play an essential role in spatial pattern separation, a process critical for accurate discrimination between similar locations. Objective: We examined differences in spatial pattern separation performance between older adults with amnestic mild cognitive impairment (aMCI) with AD versus those with non-Alzheimer's pathologic change (non-AD) and interrelations between volumes of the hippocampal, EC subregions and BF nuclei projecting to these subregions (medial septal nuclei and vertical limb of the diagonal band of Broca - Ch1-2 nuclei) with respect to performance. Methods: Hundred and eighteen older adults were recruited from the Czech Brain Aging Study. Participants with AD aMCI (n = 37), non-AD aMCI (n = 26), mild AD dementia (n = 26), and cognitively normal older adults (CN; n = 29) underwent spatial pattern separation testing, cognitive assessment and brain magnetic resonance imaging. Results: The AD aMCI group had less accurate spatial pattern separation performance than the non-AD aMCI (p = 0.039) and CN (p < 0.001) groups. The AD aMCI and non-AD groups did not differ in other cognitive tests. Decreased BF Ch1-2 volume was indirectly associated with worse performance through reduced hippocampal tail volume and reduced posteromedial EC and hippocampal tail or body volumes operating in serial. Conclusion: The study demonstrates that spatial pattern separation testing differentiates AD biomarker positive and negative older adults with aMCI and provides evidence that BF Ch1-2 nuclei influence spatial pattern separation through the posteromedial EC and the posterior hippocampus.

Keywords: amyloid-β; basal forebrain; cerebrospinal fluid; entorhinal cortex; hippocampus; magnetic resonance imaging; memory; positron emission tomography.