title: Unrecognized preclinical Alzheimer disease confounds rs-fcMRI studies of normal aging.
abstract: OBJECTIVE
  To determine whether, and to what degree, preclinical Alzheimer disease (AD) confounds studies of healthy aging where "healthy" is based on cognitive normality alone.
  
  
  METHODS
  We examined the effects of preclinical AD in cognitively normal older individuals using resting-state functional connectivity MRI. We investigated 2 groups of cognitively normal participants: one group with evidence of preclinical AD as assessed by CSF markers of AD and the other group with normal CSF biomarkers.
  
  
  RESULTS
  There were significant interactions between age and biomarker status in the default-mode, dorsal attention, and salience resting-state networks. In the group with evidence of preclinical AD, there were dramatic changes in functional connectivity with age. In the group without evidence of preclinical AD, those changes were greatly attenuated. In most regions with significant interactions of age and biomarker status, the age-related change in functional connectivity in the normal biomarker group was indistinguishable from zero.
  
  
  CONCLUSIONS
  These results suggest that preclinical AD accounts for a substantial portion of the reported effects of aging in the extant functional connectivity literature.
authors.affiliation: From the Program in Neuroscience, Division of Biological and Biomedical Science (M.R.B.), and Departments of Neurology (J.B.T., A.Z.S., L.W., A.M.F., J.C.M., B.M.A.) and Radiology (A.Z.S., T.B., B.M.A.), School of Medicine, Washington University in St. Louis; and Hope Center for Neurological Disorders (A.M.F., T.B., B.M.A.), Knight Alzheimer's Disease Research Center (A.M.F., T.B., J.C.M., B.M.A.), and Department of Biomedical Engineering (B.M.A.), Washington University in St. Louis, MO. brierm@wusm.wustl.edu.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Brier
authors.affiliation: From the Program in Neuroscience, Division of Biological and Biomedical Science (M.R.B.), and Departments of Neurology (J.B.T., A.Z.S., L.W., A.M.F., J.C.M., B.M.A.) and Radiology (A.Z.S., T.B., B.M.A.), School of Medicine, Washington University in St. Louis; and Hope Center for Neurological Disorders (A.M.F., T.B., B.M.A.), Knight Alzheimer's Disease Research Center (A.M.F., T.B., J.C.M., B.M.A.), and Department of Biomedical Engineering (B.M.A.), Washington University in St. Louis, MO.
authors.forename: Jewell B
authors.initials: JB
authors.lastname: Thomas
authors.affiliation: From the Program in Neuroscience, Division of Biological and Biomedical Science (M.R.B.), and Departments of Neurology (J.B.T., A.Z.S., L.W., A.M.F., J.C.M., B.M.A.) and Radiology (A.Z.S., T.B., B.M.A.), School of Medicine, Washington University in St. Louis; and Hope Center for Neurological Disorders (A.M.F., T.B., B.M.A.), Knight Alzheimer's Disease Research Center (A.M.F., T.B., J.C.M., B.M.A.), and Department of Biomedical Engineering (B.M.A.), Washington University in St. Louis, MO.
authors.forename: Abraham Z
authors.initials: AZ
authors.lastname: Snyder
authors.affiliation: From the Program in Neuroscience, Division of Biological and Biomedical Science (M.R.B.), and Departments of Neurology (J.B.T., A.Z.S., L.W., A.M.F., J.C.M., B.M.A.) and Radiology (A.Z.S., T.B., B.M.A.), School of Medicine, Washington University in St. Louis; and Hope Center for Neurological Disorders (A.M.F., T.B., B.M.A.), Knight Alzheimer's Disease Research Center (A.M.F., T.B., J.C.M., B.M.A.), and Department of Biomedical Engineering (B.M.A.), Washington University in St. Louis, MO.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: From the Program in Neuroscience, Division of Biological and Biomedical Science (M.R.B.), and Departments of Neurology (J.B.T., A.Z.S., L.W., A.M.F., J.C.M., B.M.A.) and Radiology (A.Z.S., T.B., B.M.A.), School of Medicine, Washington University in St. Louis; and Hope Center for Neurological Disorders (A.M.F., T.B., B.M.A.), Knight Alzheimer's Disease Research Center (A.M.F., T.B., J.C.M., B.M.A.), and Department of Biomedical Engineering (B.M.A.), Washington University in St. Louis, MO.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fagan
authors.affiliation: From the Program in Neuroscience, Division of Biological and Biomedical Science (M.R.B.), and Departments of Neurology (J.B.T., A.Z.S., L.W., A.M.F., J.C.M., B.M.A.) and Radiology (A.Z.S., T.B., B.M.A.), School of Medicine, Washington University in St. Louis; and Hope Center for Neurological Disorders (A.M.F., T.B., B.M.A.), Knight Alzheimer's Disease Research Center (A.M.F., T.B., J.C.M., B.M.A.), and Department of Biomedical Engineering (B.M.A.), Washington University in St. Louis, MO.
authors.forename: Tammie
authors.initials: T
authors.lastname: Benzinger
authors.affiliation: From the Program in Neuroscience, Division of Biological and Biomedical Science (M.R.B.), and Departments of Neurology (J.B.T., A.Z.S., L.W., A.M.F., J.C.M., B.M.A.) and Radiology (A.Z.S., T.B., B.M.A.), School of Medicine, Washington University in St. Louis; and Hope Center for Neurological Disorders (A.M.F., T.B., B.M.A.), Knight Alzheimer's Disease Research Center (A.M.F., T.B., J.C.M., B.M.A.), and Department of Biomedical Engineering (B.M.A.), Washington University in St. Louis, MO.
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.affiliation: From the Program in Neuroscience, Division of Biological and Biomedical Science (M.R.B.), and Departments of Neurology (J.B.T., A.Z.S., L.W., A.M.F., J.C.M., B.M.A.) and Radiology (A.Z.S., T.B., B.M.A.), School of Medicine, Washington University in St. Louis; and Hope Center for Neurological Disorders (A.M.F., T.B., B.M.A.), Knight Alzheimer's Disease Research Center (A.M.F., T.B., J.C.M., B.M.A.), and Department of Biomedical Engineering (B.M.A.), Washington University in St. Louis, MO.
authors.forename: Beau M
authors.initials: BM
authors.lastname: Ances
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000134:cerebrospinal fluid / Q000502:physiology*; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000503:physiopathology*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002540:Cerebral Cortex / Q000502:physiology / Q000503:physiopathology*; D005260:Female; D059907:Functional Neuroimaging / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000502:physiology / Q000503:physiopathology*; D062706:Prodromal Symptoms
chemical_list: D015415:Biomarkers