title: Longitudinal relationships among biomarkers for Alzheimer disease in the Adult Children Study.
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.
authors.affiliation: 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.
authors.forename: Chengjie
authors.initials: C
authors.lastname: Xiong
authors.affiliation: 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.
authors.forename: Mateusz S
authors.initials: MS
authors.lastname: Jasielec
authors.affiliation: 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.
authors.forename: Hua
authors.initials: H
authors.lastname: Weng
authors.affiliation: 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.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fagan
authors.affiliation: 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.
authors.forename: Tammie L S
authors.initials: TL
authors.lastname: Benzinger
authors.affiliation: 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.
authors.forename: Denise
authors.initials: D
authors.lastname: Head
authors.affiliation: 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.
authors.forename: Jason
authors.initials: J
authors.lastname: Hassenstab
authors.affiliation: 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.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Grant
authors.affiliation: 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.
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Sutphen
authors.affiliation: 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.
authors.forename: Virginia
authors.initials: V
authors.lastname: Buckles
authors.affiliation: 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.
authors.forename: Krista L
authors.initials: KL
authors.lastname: Moulder
authors.affiliation: 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.
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
mesh_terms: D000328:Adult; D032721:Adult Children; D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000378:metabolism* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D003071:Cognition; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D049268:Positron-Emission Tomography; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins