title: Early and late change on the preclinical Alzheimer's cognitive composite in clinically normal older individuals with elevated amyloid β.
abstract: BACKGROUND
  Sensitive detection of cognitive decline over the course of preclinical Alzheimer's disease is critical as the field moves toward secondary prevention trials.
  
  
  METHODS
  We examined amyloid β (Aβ)-related change in several variations of the preclinical Alzheimer cognitive composite (PACC) and each individual PACC component in clinically normal (CN) older participants in the Harvard Aging Brain Study. We then examined the PACC variations in the Alzheimer's Disease Cooperative Study Prevention Instrument Study as a replication cohort.
  
  
  RESULTS
  Aβ+ CN individuals demonstrated longitudinal decline on all individual PACC components and all PACC variations. Aβ group differences emerged earlier when Free and Cued Selective Reminding Test Free Recall was included in the PACC. PACC decline was associated with Clinical Dementia Rating progression.
  
  
  CONCLUSIONS
  This independent data set and a replication cohort confirm the ability of the PACC to capture both early and late cognitive decline during the preclinical stages of Alzheimer's disease, which may prove advantageous in the prevention trial design.
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Mormino
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Kathryn V
authors.initials: KV
authors.lastname: Papp
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Dorene M
authors.initials: DM
authors.lastname: Rentz
authors.affiliation: Department of Neurology, Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Donohue
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Amariglio
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Yakeel T
authors.initials: YT
authors.lastname: Quiroz
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jasmeer
authors.initials: J
authors.lastname: Chhatwal
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Gad A
authors.initials: GA
authors.lastname: Marshall
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Donovan
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Jackson
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Gatchel
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Hanseeuw
authors.affiliation: Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Schultz
authors.affiliation: Department of Neurology, Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Johnson
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: reisa@rics.bwh.harvard.edu.
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D001057:Apolipoproteins E / Q000235:genetics; D058070:Asymptomatic Diseases; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D001057:Apolipoproteins E; D013844:Thiazoles
keywords: Amyloid PET; Cognitive composite; Longitudinal cognitive decline; Preclinical Alzheimer's disease; Secondary prevention