Spatial navigation questionnaires as a supportive diagnostic tool in early Alzheimer's disease

Abstract

Background: Impaired spatial navigation is an early marker of Alzheimer's disease (AD), but the utility of reported navigation abilities is poorly understood. We examined the ability of self- and informant-reported spatial navigation questionnaires to discriminate between clinically and AD biomarker-defined participants from the Czech Brain Aging Study (CBAS). The associations of the questionnaires with objective measures of spatial navigation, atrophy of AD-related brain regions, AD biomarker abnormalities, and biomarker status were also examined. Methods: In total, we recruited 262 CBAS participants, including 41 cognitively normal (CN) older adults and 221 participants from the memory clinic cohort with subjective cognitive decline (SCD, n=76), amnestic mild cognitive impairment (aMCI, n=117), and mild dementia (n=28). Participants and their informants completed three spatial navigation questionnaires. Cognitive functions, spatial navigation using real-space and computerized versions of a human analog of the Morris Water Maze, and MRI-derived volume or thickness of six AD-related brain regions were assessed. Biomarker assessment, including measurement of amyloid-β1-42, p-tau181, and total tau in cerebrospinal fluid or dual-phase amyloid PET imaging or both, was performed in a subset of the memory clinic cohort (n=137) to stratify participants by amyloid-β and AT(N) status. Results: Informant-reported spatial navigation questionnaires distinguished participants with aMCI and mild dementia from CN participants, and amyloid-β positive aMCI participants from amyloid-β negative aMCI and CN participants. In contrast, informant-reported spatial navigation abilities were similar in amyloid-β negative aMCI and CN participants. Among participants in the memory clinic cohort (i.e., SCD, aMCI and mild dementia), informant-reported poorer spatial navigation abilities were associated with less accurate performance on real-space and computerized spatial navigation tasks, greater atrophy of the posterior hippocampus and the posteromedial entorhinal cortex, greater AD biomarker abnormalities, and amyloid-β positive status. Self-reported spatial navigation abilities were similar across all participant groups and were not associated with atrophy of AD-related brain regions, AD biomarker abnormalities, or biomarker status. Next, self—reported spatial navigation abilities were only weakly associated with objective measures of spatial navigation. Conclusions: Informant-reported spatial navigation questionnaires may be a useful screening tool for early AD in clinical settings, reflecting atrophy of AD-related brain regions and AD pathology.