title: Cognitive impairment and decline in cognitively normal older adults with high amyloid-β: A meta-analysis.
abstract: BACKGROUND
  This meta-analysis aimed to characterize the nature and magnitude of amyloid (Aβ)-related cognitive impairment and decline in cognitively normal (CN) older individuals.
  
  
  METHODS
  MEDLINE Ovid was searched from 2012 to June 2016 for studies reporting relationships between cerebrospinal fluid or positron emission tomography (PET) Aβ levels and cognitive impairment (cross-sectional) and decline (longitudinal) in CN older adults. Neuropsychological data were classified into domains of episodic memory, executive function, working memory, processing speed, visuospatial function, semantic memory, and global cognition. Type of Aβ measure, how Aβ burden was analyzed, inclusion of control variables, and clinical criteria used to exclude participants, were considered as moderators. Random-effects models were used for analyses with effect sizes expressed as Cohen'sd.
  
  
  RESULTS
  A total of 38 studies met inclusion criteria contributing 30 cross-sectional (N= 5005) and 14 longitudinal (N= 2584) samples. Aβ-related cognitive impairment was observed for global cognition (d= 0.32), visuospatial function (d= 0.25), processing speed (d= 0.18), episodic memory, and executive function (bothd's = 0.15), with decline observed for global cognition (d= 0.30), semantic memory (d= 0.28), visuospatial function (d= 0.25), and episodic memory (d= 0.24). Aβ-related impairment was moderated by age, amyloid measure, type of analysis, and inclusion of control variables and decline moderated by amyloid measure, type of analysis, inclusion of control variables, and exclusion criteria used.
  
  
  CONCLUSIONS
  CN older adults with high Aβ show a small general cognitive impairment and small to moderate decline in episodic memory, visuospatial function, semantic memory, and global cognition.
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; CRC for Mental Health, Carlton South, Victoria, Australia.
authors.forename: Jenalle E
authors.initials: JE
authors.lastname: Baker
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Cogstate Ltd., Melbourne, Victoria, Australia.
authors.forename: Yen Ying
authors.initials: YY
authors.lastname: Lim
authors.affiliation: U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Pietrzak
authors.affiliation: Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA; Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Hassenstab
authors.affiliation: Department of Neurology, Warren Alpert School of Medicine, Brown University, Providence, RI, USA; Department of Neurology, Rhode Island Hospital & Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Snyder
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; CRC for Mental Health, Carlton South, Victoria, Australia; Cogstate Ltd., Melbourne, Victoria, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Maruff
keywords: Amyloid-beta; Cognition; Decline; Impairment; Meta-analysis; Preclinical Alzheimer's disease