Spatial cognition is associated with levels of phosphorylated-tau and β-amyloid in clinically normal older adults

Abstract

Spatial cognition is associated with Alzheimer's disease (AD) biomarkers in the symptomatic stages of the disease. We investigated whether cerebrospinal fluid (CSF) biomarkers (phosphorylated-tau [p-tau] and β-amyloid) are associated with poorer spatial cognition in clinically normal older adults. Participants were 1875 clinically normal adults (age 67.8 [8.5] years) from the European Prevention of Alzheimer's Dementia Consortium. Mixed effect models assessed the cross-sectional association between p-tau₁₈₁, β-amyloid_1-42 (Aβ_1-42) and p-tau₁₈₁/Aβ_1-42 ratio and spatial cognition measured using semi-automated Supermarket Task and the 4 Mountains Task. Levels of p-tau₁₈₁, Aβ_1-42, and p-tau₁₈₁/Aβ_1-42 ratio were significantly associated with spatial cognition scores on both tasks. The p-tau₁₈₁/Aβ_1-42 ratio showed the largest effect sizes (β = -0.04/0.05, p < 0.001). Lower entorhinal cortical volume was associated with poorer outcomes on both tasks (β = 0.06, p < 0.002) and accounted for 18%-22% of the direct association between p-tau₁₈₁ and spatial cognition scores. In conclusion, degeneration of the entorhinal cortex mediates a significant proportion of the association between p-tau₁₈₁ and spatial assessments in cognitively normal adults. Future studies should focus on increasing the sensitivity of digital spatial assessments.

Keywords: Amyloid beta; Cerebrospinal fluid (CSF); Digital technology; Preclinical Alzheimer's disease; Spatial cognition; Tau.