title: Cued memory decline in biomarker-defined preclinical Alzheimer disease.
abstract: OBJECTIVE
  To determine whether a decline in cued recall is observable in the preclinical stage of Alzheimer disease (AD) in clinically normal older adults with elevated β-amyloid (Aβ) burden on PET imaging.
  
  
  METHODS
  Clinically normal older adults underwent baseline neuroimaging (PET to assess Aβ+/-status and MRI) and annual neuropsychological testing. Cox proportional hazards models were used to assess the relative risk of cued memory decline (drop of 1, 2, 3, or 4 points on the total score of the Free and Cued Selective Reminding Test) in relation to neuroimaging measures, functional status, age, sex, and education.
  
  
  RESULTS
  A total of 276 older adults (Clinical Dementia Rating = 0, mean Mini-Mental State Examination score = 29 ± 1.06) were followed up for a mean of 3.6 ± 1.2 years. Despite the infrequency of cued memory decline (only 19% of participants scored ≤46/48 in total recall by year 3), Aβ+participants were 3.55 times (95% confidence interval = 1.77-7.12) more likely to exhibit decline in total recall (≤46/48) compared with their Aβ-peers. Furthermore, Aβ+participants who scored ≤46/48 had smaller hippocampal volumes (t= 3.37,p= 0.001) and evidence of early functional decline, i.e., greater risk of progression to global Clinical Dementia Rating of 0.5 (χ2= 14.30,p< 0.001), compared with their Aβ+peers with intact total recall.
  
  
  CONCLUSIONS
  Cued memory decline in healthy older adults may be particularly indicative of Aβ-related decline during the preclinical stage of AD and useful for identifying Aβ+clinically normal individuals at greatest risk of short-term clinical progression.
authors.affiliation: From the Center for Alzheimer Research and Treatment (K.V.P., D.M.R., R.E.A., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Department of Neurology (D.M.R., E.C.M., A.P.S., K.A.J., R.A.S.), Department of Psychiatry (Y.Q.), and Division of Nuclear Medicine and Molecular Imaging (K.A.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; and Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Massachusetts General Hospital, Charlestown. kpapp@partners.org.
authors.forename: Kathryn V
authors.initials: KV
authors.lastname: Papp
authors.affiliation: From the Center for Alzheimer Research and Treatment (K.V.P., D.M.R., R.E.A., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Department of Neurology (D.M.R., E.C.M., A.P.S., K.A.J., R.A.S.), Department of Psychiatry (Y.Q.), and Division of Nuclear Medicine and Molecular Imaging (K.A.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; and Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Massachusetts General Hospital, Charlestown.
authors.forename: Dorene M
authors.initials: DM
authors.lastname: Rentz
authors.affiliation: From the Center for Alzheimer Research and Treatment (K.V.P., D.M.R., R.E.A., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Department of Neurology (D.M.R., E.C.M., A.P.S., K.A.J., R.A.S.), Department of Psychiatry (Y.Q.), and Division of Nuclear Medicine and Molecular Imaging (K.A.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; and Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Massachusetts General Hospital, Charlestown.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Mormino
authors.affiliation: From the Center for Alzheimer Research and Treatment (K.V.P., D.M.R., R.E.A., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Department of Neurology (D.M.R., E.C.M., A.P.S., K.A.J., R.A.S.), Department of Psychiatry (Y.Q.), and Division of Nuclear Medicine and Molecular Imaging (K.A.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; and Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Massachusetts General Hospital, Charlestown.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Schultz
authors.affiliation: From the Center for Alzheimer Research and Treatment (K.V.P., D.M.R., R.E.A., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Department of Neurology (D.M.R., E.C.M., A.P.S., K.A.J., R.A.S.), Department of Psychiatry (Y.Q.), and Division of Nuclear Medicine and Molecular Imaging (K.A.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; and Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Massachusetts General Hospital, Charlestown.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Amariglio
authors.affiliation: From the Center for Alzheimer Research and Treatment (K.V.P., D.M.R., R.E.A., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Department of Neurology (D.M.R., E.C.M., A.P.S., K.A.J., R.A.S.), Department of Psychiatry (Y.Q.), and Division of Nuclear Medicine and Molecular Imaging (K.A.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; and Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Massachusetts General Hospital, Charlestown.
authors.forename: Yakeel
authors.initials: Y
authors.lastname: Quiroz
authors.affiliation: From the Center for Alzheimer Research and Treatment (K.V.P., D.M.R., R.E.A., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Department of Neurology (D.M.R., E.C.M., A.P.S., K.A.J., R.A.S.), Department of Psychiatry (Y.Q.), and Division of Nuclear Medicine and Molecular Imaging (K.A.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; and Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Massachusetts General Hospital, Charlestown.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Johnson
authors.affiliation: From the Center for Alzheimer Research and Treatment (K.V.P., D.M.R., R.E.A., K.A.J., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Department of Neurology (D.M.R., E.C.M., A.P.S., K.A.J., R.A.S.), Department of Psychiatry (Y.Q.), and Division of Nuclear Medicine and Molecular Imaging (K.A.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; and Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Massachusetts General Hospital, Charlestown.
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology*; D000682:Amyloid / Q000378:metabolism*; D000814:Aniline Compounds / Q000493:pharmacokinetics; D015415:Biomarkers / Q000378:metabolism; D003463:Cues; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011939:Mental Recall / Q000502:physiology; D008609:Mental Status Schedule; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D013844:Thiazoles / Q000493:pharmacokinetics
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D000814:Aniline Compounds; D015415:Biomarkers; D013844:Thiazoles