Longitudinal relationships among biomarkers for Alzheimer disease in the Adult Children Study

Objective: To determine whether and how longitudinal rates of change in MRI volumetrics, CSF concentrations of Alzheimer-related proteins, molecular imaging of cerebral fibrillar amyloid with PET using the [ 11 C] benzothiazole tracer, Pittsburgh compound B (PiB), and cognition were associated among asymptomatic middle-aged to older individuals. Methods: Multivariate mixed models for repeated measures were used to assess the correlations on the rates of changes across markers. Results: Among 209 asymptomatic middle-aged to older individuals longitudinally followed for up to 11 years (mean 6.7 years), a faster intraindividual decrease in CSF Aβ 42 was associated with a faster increase in PiB mean cortical standardized uptake value ratio (MCSUVR, p 0.04), but not others. The rate of change in CSF tau (and Ptau 181) was correlated with the rate of change in PiB MCSUVR (p 0.002), hippocampal volume (p 0.04), and global cognition (p 0.008). The rate of change in hippocampal volume was correlated with the rate of change in global cognition (p 0.04). Only 3 significant correlations were observed at baseline: CSF Aβ 42 and PiB MCSUVR (p < 0.001), CSF tau and PiB MCSUVR (p < 0.001), and CSF Aβ 42 and global cognition (p 0.01). Conclusions: CSF tau (Ptau 181), PiB MCSUVR, and hippocampal volume were all longitudinally correlated with each other, whereas CSF Aβ 42 was correlated only with PiB binding. Unlike the baseline values, the longitudinal change in CSF tau (Ptau 181) and hippocampal volume were correlated with the longitudinal change in global cognition, validating the role of these biomarkers in Alzheimer disease prevention trials.