title: Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease.
abstract: The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from "normal" cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease-modifying therapies may be most efficacious.
authors.affiliation: Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. reisa@rics.bwh.harvard.edu
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Beckett
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
authors.forename: Suzanne
authors.initials: S
authors.lastname: Craft
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fagan
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwatsubo
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kaye
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.forename: Denise C
authors.initials: DC
authors.lastname: Park
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
authors.forename: Eric
authors.initials: E
authors.lastname: Siemers
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Stern
authors.forename: Kristine
authors.initials: K
authors.lastname: Yaffe
authors.forename: Maria C
authors.initials: MC
authors.lastname: Carrillo
authors.forename: Bill
authors.initials: B
authors.lastname: Thies
authors.forename: Marcelle
authors.initials: M
authors.lastname: Morrison-Bogorad
authors.forename: Molly V
authors.initials: MV
authors.lastname: Wagster
authors.forename: Creighton H
authors.initials: CH
authors.lastname: Phelps
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis* / Q000503:physiopathology / Q000523:psychology; D015415:Biomarkers / Q000032:analysis; D003072:Cognition Disorders / Q000175:diagnosis* / Q000503:physiopathology / Q000523:psychology; D006801:Humans; D054561:National Institute on Aging (U.S.) / Q000592:standards*; D017410:Practice Guidelines as Topic / Q000592:standards*; D014481:United States
chemical_list: D015415:Biomarkers