PMID- 26827648 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20181113 IS - 1558-1497 (Electronic) IS - 0197-4580 (Print) IS - 0197-4580 (Linking) VI - 38 DP - 2016 Feb TI - Local and distributed PiB accumulation associated with development of preclinical Alzheimer's disease. PG - 104-111 LID - S0197-4580(15)00537-0 [pii] LID - 10.1016/j.neurobiolaging.2015.10.025 [doi] AB - 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. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Brier, Matthew R AU - Brier MR AD - Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA. FAU - McCarthy, John E AU - McCarthy JE AD - Department of Mathematics, Washington University School of Medicine, St. Louis, MO, USA. FAU - Benzinger, Tammie L S AU - Benzinger TLS AD - 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. FAU - Stern, Ari AU - Stern A AD - Department of Mathematics, Washington University School of Medicine, St. Louis, MO, USA. FAU - Su, Yi AU - Su Y AD - Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA. FAU - Friedrichsen, Karl A AU - Friedrichsen KA AD - Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA. FAU - Morris, John C AU - Morris JC AD - 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. FAU - Ances, Beau M AU - Ances BM AD - 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. FAU - Vlassenko, Andrei G AU - Vlassenko AG AD - 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. LA - eng GR - R01 AG043434/AG/NIA NIH HHS/United States GR - R21 MH099979/MH/NIMH NIH HHS/United States GR - P01AG026276/AG/NIA NIH HHS/United States GR - 1R01NR012657/NR/NINR NIH HHS/United States GR - 5P01AG026276/AG/NIA NIH HHS/United States GR - P01 AG003991/AG/NIA NIH HHS/United States GR - P50 AG005681/AG/NIA NIH HHS/United States GR - P01 AG026276/AG/NIA NIH HHS/United States GR - R01 NR012907/NR/NINR NIH HHS/United States GR - 1R21MH099979/MH/NIMH NIH HHS/United States GR - R01 EB009352/EB/NIBIB NIH HHS/United States GR - P30 NS098577/NS/NINDS NIH HHS/United States GR - R01 NR014449/NR/NINR NIH HHS/United States GR - P30 NS048056/NS/NINDS NIH HHS/United States GR - R01 NR012657/NR/NINR NIH HHS/United States GR - UL1 TR000448/TR/NCATS NIH HHS/United States GR - 1R01NR012907/NR/NINR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20151031 PL - United States TA - Neurobiol Aging JT - Neurobiology of aging JID - 8100437 RN - 0 (2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole) RN - 0 (Amyloid beta-Peptides) RN - 0 (Aniline Compounds) RN - 0 (Thiazoles) SB - IM MH - Aged MH - Aged, 80 and over MH - Alzheimer Disease/diagnosis/*metabolism/pathology MH - Amyloid beta-Peptides/*metabolism MH - *Aniline Compounds MH - Brain/*metabolism MH - Female MH - Follow-Up Studies MH - Humans MH - Longitudinal Studies MH - Magnetic Resonance Imaging MH - Male MH - Middle Aged MH - Multivariate Analysis MH - Neuroimaging MH - Plaque, Amyloid/metabolism/pathology MH - Positron-Emission Tomography MH - *Thiazoles MH - Tissue Distribution PMC - PMC5279747 MID - NIHMS830816 OTO - NOTNLM OT - Amyloid beta OT - Canonical correlation OT - Lasso OT - Multivariate statistics COIS- statement The authors report no conflict of interest. This study was funded by the NIH as specified in the acknowledgements. EDAT- 2016/02/02 06:00 MHDA- 2016/12/15 06:00 PMCR- 2017/02/01 CRDT- 2016/02/02 06:00 PHST- 2015/08/10 00:00 [received] PHST- 2015/10/23 00:00 [revised] PHST- 2015/10/26 00:00 [accepted] PHST- 2016/02/02 06:00 [entrez] PHST- 2016/02/02 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] PHST- 2017/02/01 00:00 [pmc-release] AID - S0197-4580(15)00537-0 [pii] AID - 10.1016/j.neurobiolaging.2015.10.025 [doi] PST - ppublish SO - Neurobiol Aging. 2016 Feb;38:104-111. doi: 10.1016/j.neurobiolaging.2015.10.025. Epub 2015 Oct 31.