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

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:...

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Autores principales: Martina Laczó, Ondrej Lerch, Lukas Martinkovic, Jana Kalinova, Hana Markova, Martin Vyhnalek, Jakub Hort, Jan Laczó
Formato: article
Lenguaje:EN
Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/cbec0812a0db4f8798f34506e58a624d
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Sumario: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.