Meta‐analysis of the associations of biomarkers of amyloid and tau with cognition in cognitively normal older adults

Abstract

AbstractBackgroundConflicting evidence exists on the in vivo relationship of amyloid and tau levels to cognition among cognitively normal older adults. We conducted a meta‐analysis of reported relationships of biomarkers of amyloid or tau levels with baseline and change in cognition in cognitively normal older adults.MethodWe performed a literature search that returned studies between 2005 and January 2021 for studies reporting a relationship between amyloid or tau biomarkers measured via PET ligands, CSF, or plasma assays, with episodic memory or global cognition. Effect sizes were obtained for each study and weighted by sample size. For studies examining the same cohort, we selected effect sizes from the largest sample size available for each relationship of interest.ResultOne hundred and seven studies (89% reporting cross sectional measures and 62% reporting longitudinal) representing 26968 adults (82% characterized with amyloid measures and 23% with tau) were included. Amyloid levels showed a significant correlation with baseline and longitudinal global cognition (r=0.05, p<0001; r=0.05, p=0.021, respectively), and with baseline episodic memory (r=0.05, p=0.001). Tau was significantly correlated with baseline and longitudinal global cognition (r=0.08, p=0.004; r=0.08, p=0.01, respectively), and with longitudinal episodic memory (r=0.02, p=0.04), whereas the interaction of amyloid and tau was significantly correlated only with baseline global cognition (r=0.09, p=0.024). The overall estimated correlation between amyloid and tau was r=0.17.ConclusionIn older adults with normal cognition, there is a very small but significant relationship between baseline global cognition and amyloid, tau, and their interactive effect. Episodic memory had a very small but significant relationship with amyloid at baseline and with tau longitudinally. These findings could help determine power estimations for future clinical trials evaluating cognition in asymptomatic older adults. Effect size and power estimations from this meta‐analysis may be limited by unmeasured variability among studies in the timing of biomarker measurement, differences in cognitive assessments, or other cohort‐specific differences.