The Maze of Alzheimer’s: Exploring Spatial Navigation Deficits in Biomarker-Positive & Negative Older Adults with Amnestic Mild Cognitive Impairment

Published on June 2, 2022

Imagine navigating a complex maze, trying to find your way through its twists and turns. Now, picture the brain of someone with Alzheimer’s disease, facing its own maze of challenges — spatial navigation deficits. In a recent study, researchers compared the performance of older adults with Alzheimer’s biomarkers to those without, specifically focusing on amnestic mild cognitive impairment (aMCI). The results revealed distinct profiles of spatial navigation deficits between the two groups. Participants with Alzheimer’s biomarkers struggled more in route learning and perspective taking/wayfinding tasks compared to their biomarker-negative counterparts. Additionally, wayfinding performance declined across sessions for aMCI participants with Alzheimer’s biomarkers. These deficits were linked to brain regions associated with memory (posterior medial temporal lobe) and attention (parietal cortex), as revealed by MRI measures of atrophy. The study shed light on the connection between spatial navigation impairment and underlying Alzheimer’s pathology. To delve deeper into this fascinating research, check out the full article!

BackgroundSpatial navigation impairment is a promising cognitive marker of Alzheimer’s disease (AD) that can reflect the underlying pathology.ObjectivesWe assessed spatial navigation performance in AD biomarker positive older adults with amnestic mild cognitive impairment (AD aMCI) vs. those AD biomarker negative (non-AD aMCI), and examined associations between navigation performance, MRI measures of brain atrophy, and cerebrospinal fluid (CSF) biomarkers.MethodsA total of 122 participants with AD aMCI (n = 33), non-AD aMCI (n = 31), mild AD dementia (n = 28), and 30 cognitively normal older adults (CN) underwent cognitive assessment, brain MRI (n = 100 had high-quality images for volumetric analysis) and three virtual navigation tasks focused on route learning (body-centered navigation), wayfinding (world-centered navigation) and perspective taking/wayfinding. Cognitively impaired participants underwent CSF biomarker assessment [amyloid-β1–42, total tau, and phosphorylated tau181 (p-tau181)] and amyloid PET imaging (n = 47 and n = 45, respectively), with a subset having both (n = 19).ResultsIn route learning, AD aMCI performed worse than non-AD aMCI (p < 0.001), who performed similarly to CN. In wayfinding, aMCI participants performed worse than CN (both p ≤ 0.009) and AD aMCI performed worse than non-AD aMCI in the second task session (p = 0.032). In perspective taking/wayfinding, aMCI participants performed worse than CN (both p ≤ 0.001). AD aMCI and non-AD aMCI did not differ in conventional cognitive tests. Route learning was associated with parietal thickness and amyloid-β1–42, wayfinding was associated with posterior medial temporal lobe (MTL) volume and p-tau181 and perspective taking/wayfinding was correlated with MRI measures of several brain regions and all CSF biomarkers.ConclusionAD biomarker positive and negative older adults with aMCI had different profiles of spatial navigation deficits that were associated with posterior MTL and parietal atrophy and reflected AD pathology.

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