AUTHOR=Laczó Martina , Martinkovic Lukas , Lerch Ondrej , Wiener Jan M. , Kalinova Jana , Matuskova Veronika , Nedelska Zuzana , Vyhnalek Martin , Hort Jakub , Laczó Jan 

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 14 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.886778

DOI=10.3389/fnagi.2022.886778

ISSN=1663-4365

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) versus those AD biomarker negative (non-AD aMCI), and examined associations between navigation performance, MRI measures of brain atrophy and cerebrospinal fluid (CSF) biomarkers.
Methods: 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).
Results: In route learning, AD aMCI performed worse than non-AD aMCI (p<.001), who performed similarly to CN. In wayfinding, aMCI participants performed worse than CN (both p≤.009) and AD aMCI performed worse than non-AD aMCI in the second task session (p=.032). In perspective taking/wayfinding, aMCI participants performed worse than CN (both p≤.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.
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.