AUTHOR=Laczó Martina , Lerch Ondrej , Martinkovic Lukas , Kalinova Jana , Markova Hana , Vyhnalek Martin , Hort Jakub , Laczó Jan 

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=13

YEAR=2021

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.774600

DOI=10.3389/fnagi.2021.774600

ISSN=1663-4365

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Objective:</bold> 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.</p><p><bold>Methods:</bold> Hundred and eighteen older adults were recruited from the Czech Brain Aging Study. Participants with AD aMCI (<italic>n</italic> = 37), non-AD aMCI (<italic>n</italic> = 26), mild AD dementia (<italic>n</italic> = 26), and cognitively normal older adults (CN; <italic>n</italic> = 29) underwent spatial pattern separation testing, cognitive assessment and brain magnetic resonance imaging.</p><p><bold>Results:</bold> The AD aMCI group had less accurate spatial pattern separation performance than the non-AD aMCI (<italic>p</italic> = 0.039) and CN (<italic>p</italic> &lt; 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.</p><p><bold>Conclusion:</bold> 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.</p>