Different Profiles of Spatial Navigation Deficits In Alzheimer's Disease Biomarker-Positive Versus Biomarker-Negative Older Adults With Amnestic Mild Cognitive Impairment.

Background: Spatial navigation impairment is a promising cognitive marker of Alzheimer's disease (AD) that can reflect the underlying pathology.
Objectives: We 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.
Methods: A 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-β _1-42 , total tau, and phosphorylated tau ₁₈₁ (p-tau ₁₈₁ )] and amyloid PET imaging ( n = 47 and n = 45, respectively), with a subset having both ( n = 19).
Results: In 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-β _1-42 , wayfinding was associated with posterior medial temporal lobe (MTL) volume and p-tau ₁₈₁ and perspective taking/wayfinding was correlated with MRI measures of several brain regions and all CSF biomarkers.
Conclusion: AD 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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Laczó, Martinkovic, Lerch, Wiener, Kalinova, Matuskova, Nedelska, Vyhnalek, Hort and Laczó.)