Spatial Pattern Separation in Early Alzheimer's Disease

Abstract

Background: The hippocampus, entorhinal cortex, and basal forebrain are among the first brain structures affected by Alzheimer's disease (AD). They play an essential role in spatial pattern separation, a process critical for accurate encoding of similar spatial information.

Objective: Our aim was to examine spatial pattern separation and its association with volumetric changes of the hippocampus, entorhinal cortex, and basal forebrain nuclei projecting to the hippocampus (the medial septal nuclei and vertical limb of the diagonal band of Broca - Ch1-2 nuclei) in the biomarker-defined early clinical stages of AD.

Methods: A total of 98 older adults were recruited from the Czech Brain Aging Study cohort. The participants with amnestic mild cognitive impairment (aMCI) due to AD (n = 44), mild AD dementia (n = 31), and cognitively normal older adults (CN; n = 23) underwent spatial pattern separation testing, comprehensive cognitive assessment, and MRI brain volumetry.

Results: Spatial pattern separation accuracy was lower in the early clinical stages of AD compared to the CN group (p < 0.001) and decreased with disease severity (CN > aMCI due to AD > AD dementia). Controlling for general memory and cognitive performance, demographic characteristics and psychological factors did not change the results. Hippocampal and Ch1-2 volumes were directly associated with spatial pattern separation performance while the entorhinal cortex operated on pattern separation indirectly through the hippocampus.

Conclusion: Smaller volumes of the hippocampus, entorhinal cortex, and basal forebrain Ch1-2 nuclei are linked to spatial pattern separation impairment in biomarker-defined early clinical AD and may contribute to AD-related spatial memory deficits.

Keywords: Basal forebrain; entorhinal cortex; hippocampus; memory; mild cognitive impairment.