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=14

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=<sec><title>Background</title><p>Spatial navigation impairment is a promising cognitive marker of Alzheimer’s disease (AD) that can reflect the underlying pathology.</p></sec><sec><title>Objectives</title><p>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.</p></sec><sec><title>Methods</title><p>A total of 122 participants with AD aMCI (<italic>n</italic> = 33), non-AD aMCI (<italic>n</italic> = 31), mild AD dementia (<italic>n</italic> = 28), and 30 cognitively normal older adults (CN) underwent cognitive assessment, brain MRI (<italic>n</italic> = 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<sub>1–42</sub>, total tau, and phosphorylated tau<sub>181</sub> (p-tau<sub>181</sub>)] and amyloid PET imaging (<italic>n</italic> = 47 and <italic>n</italic> = 45, respectively), with a subset having both (<italic>n</italic> = 19).</p></sec><sec><title>Results</title><p>In route learning, AD aMCI performed worse than non-AD aMCI (<italic>p</italic> &lt; 0.001), who performed similarly to CN. In wayfinding, aMCI participants performed worse than CN (both <italic>p</italic> ≤ 0.009) and AD aMCI performed worse than non-AD aMCI in the second task session (<italic>p</italic> = 0.032). In perspective taking/wayfinding, aMCI participants performed worse than CN (both <italic>p</italic> ≤ 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<sub>1–42</sub>, wayfinding was associated with posterior medial temporal lobe (MTL) volume and p-tau<sub>181</sub> and perspective taking/wayfinding was correlated with MRI measures of several brain regions and all CSF biomarkers.</p></sec><sec><title>Conclusion</title><p>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.</p></sec>