Investigating the associations between tau and mental orientation among cognitively unimpaired individuals

Background: Impairments in orientation in space, time, and person occur frequently in Alzheimer's disease (AD) dementia. Subtle changes in orientation may arise in preclinical and prodromal disease stages. Thus, assessing orientation may help identify those on a trajectory toward AD dementia. Objective: To investigate how orientation, measured using a novel artificial intelligence-based paradigm, relates to AD biomarkers (amyloid and tau) in cognitively unimpaired older adults. Methods: Using an automated chatbot, 53 cognitively unimpaired participants (74.0 ± 5.5 years; 60% female) provided details about memories and relationships, recognition of historical event dates, and geographical locations. These details were then used to assess orientation to space, time, and person. For each domain separately, orientation accuracy was calculated by dividing the number of correct responses by response time. All participants underwent Pittsburgh compound-B (amyloid) and flortaucipir (tau) positron emission tomography. We analyzed the relationship between performance on the three orientation domains and retrosplenial, precuneus, neocortical, and medial temporal tau, and global amyloid. Results: Higher retrosplenial and precuneus tau burden were associated with worse temporal orientation (β = −0.32, 95% confidence interval [95%CI] = [−0.59, −0.05] and β = −0.29, 95%CI = [−0.57, −0.01], respectively). Spatial or social orientation were not associated with amyloid or tau. Conclusions: These results suggest that impaired temporal orientation is related to AD pathological processes, even before the onset of overt cognitive impairment, and may infer a role for personalized assessment of orientation in early diagnosis of AD.