title: Local and distributed PiB accumulation associated with development of preclinical Alzheimer's disease.
abstract: Amyloid-beta plaques are a hallmark of Alzheimer's disease (AD) that can be assessed by amyloid imaging (e.g., Pittsburgh B compound [PiB]) and summarized as a scalar value. Summary values may have clinical utility but are an average over many regions of interest, potentially obscuring important topography. This study investigates the longitudinal evolution of amyloid topographies in cognitively normal older adults who had normal (N = 131) or abnormal (N = 26) PiB scans at baseline. At 3 years follow-up, 16 participants with a previously normal PiB scan had conversion to PiB scans consistent with preclinical AD. We investigated the multivariate relationship (canonical correlation) between baseline and follow-up PiB topographies. Furthermore, we used penalized regression to investigate the added information derived from PiB topography compared to summary measures. PiB accumulation can be local, that is, a topography predicting the same topography in the future, and/or distributed, that is, one topography predicting another. Both local and distributed PiB accumulation was associated with conversion of PiB status. Additionally, elements of the multivariate topography, and not the commonly used summary scalar, correlated with future PiB changes. Consideration of the entire multivariate PiB topography provides additional information regarding the development of amyloid-beta pathology in very early preclinical AD.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Brier
authors.affiliation: Department of Mathematics, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: McCarthy
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA; The Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Tammie L S
authors.initials: TLS
authors.lastname: Benzinger
authors.affiliation: Department of Mathematics, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Ari
authors.initials: A
authors.lastname: Stern
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Karl A
authors.initials: KA
authors.lastname: Friedrichsen
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA; The Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA; Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA; The Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: ancesb@neuro.wustl.edu.
authors.forename: Beau M
authors.initials: BM
authors.lastname: Ances
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA; The Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Andrei G
authors.initials: AG
authors.lastname: Vlassenko
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D001921:Brain / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D059906:Neuroimaging; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D049268:Positron-Emission Tomography; D013844:Thiazoles; D014018:Tissue Distribution
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D013844:Thiazoles
keywords: Amyloid beta; Canonical correlation; Lasso; Multivariate statistics
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