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

Martina Laczó; Lukas Martinkovic; Ondrej Lerch; Jan M Wiener; Jana Kalinova; Veronika Matuskova; Zuzana Nedelska; Martin Vyhnalek; Jakub Hort; Jan Laczó

doi:10.3389/fnagi.2022.886778

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

Front Aging Neurosci. 2022 Jun 2:14:886778. doi: 10.3389/fnagi.2022.886778. eCollection 2022.

Authors

Martina Laczó¹, Lukas Martinkovic¹, Ondrej Lerch^{1

2}, Jan M Wiener³, Jana Kalinova¹, Veronika Matuskova^{1

2}, Zuzana Nedelska^{1

2}, Martin Vyhnalek^{1

2}, Jakub Hort^{1

2}, Jan Laczó^{1

2}

Affiliations

¹ Memory Clinic, Department of Neurology, Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czechia.
² International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czechia.
³ Department of Psychology, Ageing and Dementia Research Centre, Bournemouth University, Poole, United Kingdom.

Abstract

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 tau₁₈₁ (p-tau₁₈₁)] 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-tau₁₈₁ 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.

Keywords: allocentric navigation; egocentric navigation; entorhinal cortex; hippocampus; neurodegeneration; precuneus; retrosplenial cortex; tauopathies.