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

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

doi:10.3389/fnagi.2021.774600

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.

Highlights

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease characterized by gradual episodic and spatial memory decline
We examined the differences in spatial pattern separation performance between AD biomarker positive and negative amnestic MCI (aMCI) participants and explored the associations between the performance and structural measures of specific hippocampal, entorhinal cortex (EC) subregions and basal forebrain (BF) Ch1-2 nuclei, and the interrelations between these regions with respect to the performance
We found that the AD aMCI participants had less accurate spatial pattern separation than the non-AD aMCI participants while performing in other cognitive tests

Summary

Introduction

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease characterized by gradual episodic and spatial memory decline. The posteromedial EC (pmEC) is involved in spatial information processing and receives projections from the parahippocampal cortex (PhC) and posterior-medial cortical regions (Navarro Schröder et al, 2015; Berron et al, 2018). These two pathways convey information to the hippocampus and contribute to object and spatial pattern separation processes (Reagh and Yassa, 2014). 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

Methods

Results

Discussion

Conclusion