No abstract

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.

Background: The hippocampus, entorhinal cortex (EC), and basal forebrain (BF) are among the earliest regions affected by Alzheimer’s disease (AD) pathology. They play an essential role in spatial pattern separation, a process critical for accurate discrimination between similar locations.Objective: We examined differences in spatial pattern separation performance between older adults with amnestic mild cognitive impairment (aMCI) with AD versus those with non-Alzheimer’s pathologic change (non-AD) and interrelations between volumes of the hippocampal, EC subregions and BF nuclei projecting to these subregions (medial septal nuclei and vertical limb of the diagonal band of Broca – Ch1-2 nuclei) with respect to performance.Methods: Hundred and eighteen older adults were recruited from the Czech Brain Aging Study. Participants with AD aMCI (n = 37), non-AD aMCI (n = 26), mild AD dementia (n = 26), and cognitively normal older adults (CN; n = 29) underwent spatial pattern separation testing, cognitive assessment and brain magnetic resonance imaging.Results: The AD aMCI group had less accurate spatial pattern separation performance than the non-AD aMCI (p = 0.039) and CN (p < 0.001) groups. The AD aMCI and non-AD groups did not differ in other cognitive tests. Decreased BF Ch1-2 volume was indirectly associated with worse performance through reduced hippocampal tail volume and reduced posteromedial EC and hippocampal tail or body volumes operating in serial.Conclusion: The study demonstrates that spatial pattern separation testing differentiates AD biomarker positive and negative older adults with aMCI and provides evidence that BF Ch1-2 nuclei influence spatial pattern separation through the posteromedial EC and the posterior hippocampus.

Age-related spatial navigation decline is more pronounced in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia. We used a realistic-looking virtual navigation test suite to analyze different aspects of visuospatial processing in typical and atypical aging. A total of 219 older adults were recruited from the Czech Brain Aging Study cohort. Cognitively normal older adults (CN; n = 78), patients with amnestic MCI (n = 75), and those with mild AD dementia (n = 66) underwent three navigational tasks, cognitive assessment, and brain MRI. Route learning and wayfinding/perspective-taking tasks distinguished the groups as performance and learning declined and specific visuospatial strategies were less utilized with increasing cognitive impairment. Increased perspective shift and utilization of non-specific strategies were associated with worse task performance across the groups. Primacy and recency effects were observed across the groups in the route learning and the wayfinding/perspective-taking task, respectively. In addition, a primacy effect was present in the wayfinding/perspective-taking task in the CN older adults. More effective spatial navigation was associated with better memory and executive functions. The results demonstrate that a realistic and ecologically valid spatial navigation test suite can reveal different aspects of visuospatial processing in typical and atypical aging.

Background Spatial navigation deficits are present early in Alzheimer´s disease (AD) and could thus serve as an early cognitive marker of the disease. AD patients were shown to have altered scene exploration during spatial navigation as they overlook objects of interest. We aimed to evaluate the potential of a virtual spatial navigation task and eye‐tracking assessment to identify individuals with early AD and to differentiate them from those with cognitive deficit of other etiology. Methods 48 participants: amnestic mild cognitive impairment (aMCI) with positive AD‐biomarkers (aMCI due to AD, n=14), aMCI with negative biomarkers (aMCI AD‐negative, n=8), mild AD dementia (n=9) and cognitively normal (CN) older adults (n=17) underwent clinical and neuropsychological evaluation, MRI brain scan, amyloid PET imaging, cerebrospinal fluid biomarker assessment and spatial navigation testing in a virtual realistic‐looking “Intersections” test. The test consisted of three tasks: i) egocentric “route repetition”, where participants repeated the route through a virtual city, ii) allocentric “route retracing”, where participants indicated their way back, and iii) allocentric “different approach direction” combined with eye‐tracking, where participants indicated their original position from a different perspective at each intersection with two same and two unique houses. Number of fixations and length of fixation of unique houses were analyzed. Results The aMCI due to AD and mild AD dementia groups had lower scores in the egocentric “route repetition” and allocentric “route retracing” tasks compared to the CN (p<0.012) and aMCI AD‐negative (p<0.007) groups. There were no differences between the CN and aMCI AD‐negative groups in these tasks. The AD dementia group had lower scores in the allocentric “different approach direction” task compared to the CN group (p=0.027). Duration and number of fixations of unique landmarks in the “different approach direction” was similar across all groups that demonstrated higher number and longer duration of fixations regardless of the task performance (p<0.001). Conclusion The egocentric and allocentric tasks from the virtual “Intersection” test reliably detect spatial navigation impairment typical for early stages of AD. Spatial navigation unlike scene exploration can differentiate individuals with aMCI due to AD from those with non‐AD etiology.