title: Aβ and cognitive change: examining the preclinical and prodromal stages of Alzheimer's disease.
abstract: BACKGROUND
  High β-amyloid (Aβ) is associated with faster memory decline in healthy individuals and adults with mild cognitive impairment (MCI). However, longer prospective studies are required to determine if Aβ-related memory decline continues and whether it is associated with increased rate of disease progression.
  
  
  METHODS
  Healthy controls (HCs; n = 177) and adults with MCI (n = 48) underwent neuroimaging for Aβ and cognitive assessment at baseline. Cognition was reassessed 18 and 36 months later.
  
  
  RESULTS
  Compared with low-Aβ HCs, high-Aβ HC and MCI groups showed moderate decline in episodic and working memory over 36 months. Those with MCI with low Aβ did not show any cognitive decline. Rates of disease progression were increased in the high-Aβ HC and MCI groups.
  
  
  CONCLUSIONS
  In healthy individuals, high Aβ likely indicates that Alzheimer's disease (AD)-related neurodegeneration has begun. Once commenced, the rate of decline in cognitive function remains constant across the preclinical and prodromal stages of AD.
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia. Electronic address: yen_ying_lim@brown.edu.
authors.forename: Yen Ying
authors.initials: YY
authors.lastname: Lim
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; CogState Ltd., Melbourne, Victoria, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Maruff
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Pietrzak
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, Kew, Victoria, Australia; National Ageing Research Institute, Parkville, Victoria, Australia.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Ellis
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Darby
authors.affiliation: Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, Kew, Victoria, Australia; National Ageing Research Institute, Parkville, Victoria, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
authors.forename: Karra
authors.initials: K
authors.lastname: Harrington
authors.affiliation: Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical, and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia.
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; National Ageing Research Institute, Parkville, Victoria, Australia; CSIRO Preventative Health Flagship, Parkville, Victoria, Australia.
authors.forename: Cassandra
authors.initials: C
authors.lastname: Szoeke
authors.affiliation: Department of Psychology and ARC Centre of Excellence in Cognition and Its Disorders, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Greg
authors.initials: G
authors.lastname: Savage
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000000981:diagnostic imaging; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D003072:Cognition Disorders / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000209:etiology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007858:Learning; D016014:Linear Models; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D008570:Memory, Short-Term; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D062706:Prodromal Symptoms; D011569:Psychiatric Status Rating Scales; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D013844:Thiazoles
keywords: Aβ; Cognitive decline; Neuropsychology; Preclinical AD; Prodromal AD