Chengjie Xiong1, Mateusz S Jasielec2, Hua Weng2, Anne M Fagan2, Tammie L S Benzinger2, Denise Head2, Jason Hassenstab2, Elizabeth Grant2, Courtney L Sutphen2, Virginia Buckles2, Krista L Moulder2, John C Morris2. 1. From the Charles F. and Joanne Knight Alzheimer's Disease Research Center (C.X., M.S.J., H.W., A.M.F., T.L.S.B., D.H., J.H., E.G., C.L.S., V.B., K.L.M., J.C.M.), Departments of Neurology (V.B., K.L.M., A.M.F., J.H., J.C.M., C.L.S.), Pathology and Immunology (J.C.M.), Physical Therapy (J.C.M.), and Occupational Therapy (J.C.M.), Division of Biostatistics (C.X., M.S.J., H.W., E.G.), and Departments of Psychology (D.H., J.H.), Radiology (T.L.S.B., D.H.), and Neurological Surgery (T.L.S.B.), Washington University School of Medicine, St. Louis, MO. chengjie@wubios.wustl.edu. 2. From the Charles F. and Joanne Knight Alzheimer's Disease Research Center (C.X., M.S.J., H.W., A.M.F., T.L.S.B., D.H., J.H., E.G., C.L.S., V.B., K.L.M., J.C.M.), Departments of Neurology (V.B., K.L.M., A.M.F., J.H., J.C.M., C.L.S.), Pathology and Immunology (J.C.M.), Physical Therapy (J.C.M.), and Occupational Therapy (J.C.M.), Division of Biostatistics (C.X., M.S.J., H.W., E.G.), and Departments of Psychology (D.H., J.H.), Radiology (T.L.S.B., D.H.), and Neurological Surgery (T.L.S.B.), Washington University School of Medicine, St. Louis, MO.
Abstract
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 Aβ42 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 Ptau181) 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 Aβ42 and PiB MCSUVR (p < 0.001), CSF tau and PiB MCSUVR (p < 0.001), and CSF Aβ42 and global cognition (p = 0.01). CONCLUSIONS: CSF tau (Ptau181), PiB MCSUVR, and hippocampal volume were all longitudinally correlated with each other, whereas CSF Aβ42 was correlated only with PiB binding. Unlike the baseline values, the longitudinal change in CSF tau (Ptau181) and hippocampal volume were correlated with the longitudinal change in global cognition, validating the role of these biomarkers in Alzheimer disease prevention trials.
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 Aβ42 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 CSFtau (and Ptau181) 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 Aβ42 and PiB MCSUVR (p < 0.001), CSFtau and PiB MCSUVR (p < 0.001), and CSF Aβ42 and global cognition (p = 0.01). CONCLUSIONS:CSFtau (Ptau181), PiB MCSUVR, and hippocampal volume were all longitudinally correlated with each other, whereas CSF Aβ42 was correlated only with PiB binding. Unlike the baseline values, the longitudinal change in CSFtau (Ptau181) and hippocampal volume were correlated with the longitudinal change in global cognition, validating the role of these biomarkers in Alzheimer disease prevention trials.
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