@article{f0180eb2e6b844b6ac6bf94d1d27247b,
title = "Association of brain amyloid-β with cerebral perfusion and structure in Alzheimer's disease and mild cognitive impairment",
abstract = "Patients with Alzheimer's disease have reduced cerebral blood flow measured by arterial spin labelling magnetic resonance imaging, but it is unclear how this is related to amyloid-β pathology. Using 182 subjects from the Alzheimer's Disease Neuroimaging Initiative we tested associations of amyloid-β with regional cerebral blood flow in healthy controls (n = 51), early (n = 66) and late (n = 41) mild cognitive impairment, and Alzheimer's disease with dementia (n = 24). Based on the theory that Alzheimer's disease starts with amyloid-β accumulation and progresses with symptoms and secondary pathologies in different trajectories, we tested if cerebral blood flow differed between amyloid-β-negative controls and -positive subjects in different diagnostic groups, and if amyloid-β had different associations with cerebral blood flow and grey matter volume. Global amyloid-β load was measured by florbetapir positron emission tomography, and regional blood flow and volume were measured in eight a priori defined regions of interest. Cerebral blood flow was reduced in patients with dementia in most brain regions. Higher amyloid-β load was related to lower cerebral blood flow in several regions, independent of diagnostic group. When comparing amyloid-β-positive subjects with -negative controls, we found reductions of cerebral blood flow in several diagnostic groups, including in precuneus, entorhinal cortex and hippocampus (dementia), inferior parietal cortex (late mild cognitive impairment and dementia), and inferior temporal cortex (early and late mild cognitive impairment and dementia). The associations of amyloid-β with cerebral blood flow and volume differed across the disease spectrum, with high amyloid-β being associated with greater cerebral blood flow reduction in controls and greater volume reduction in late mild cognitive impairment and dementia. In addition to disease stage, amyloid-β pathology affects cerebral blood flow across the span from controls to dementia patients. Amyloid-β pathology has different associations with cerebral blood flow and volume, and may cause more loss of blood flow in early stages, whereas volume loss dominates in late disease stages.",
keywords = "Alzheimer's disease, PET imaging, beta-amyloid, magnetic resonance imaging, perfusion imaging",
author = "Niklas Mattsson and Duygu Tosun and Insel, {Philip S.} and Alix Simonson and Jack, {Clifford R.} and Beckett, {Laurel A.} and Michael Donohue and William Jagust and Norbert Schuff and Weiner, {Michael W.}",
note = "Funding Information: Data collection and sharing for this project was funded by the Alzheimer{\textquoteright}s Disease Neuroimaging Initiative (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Ageing, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimers Association; Alzheimers Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research and Development, LLC.; Johnson and Johnson Pharmaceutical Research and Development LLC.; Medpace, Inc.; Merck and Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129 and K01 AG030514.This research was also supported by the Swedish Research Council, Goteborgs Lakaresallskap, Svenska Lakaresallskapet, Sahlgrenska Universitetssjukhuset, Carl-Bertil Laurells fond, and Klinisk Biokemi i Norden. Funding Information: N.M., P.I., D.T., A.S., M.D., W.J. and N.S. report no conflicts of interest. C.R.J. provides consulting services for Siemens Healthcare and Janssen Research and Development L.L.C. He receives research funding from the National Institutes of Health (R01-AG011378, RO1-AG041851, RO1-AG037551, U01-HL096917, U01-AG032438, U01-AG024904), and the Alexander Family Alzheimer{\textquoteright}s Disease Research Professorship of the Mayo Foundation. L.A.B. has been a consultant for F. Hoffmann-LaRoche Ltd. M.W. has been on scientific advisory boards for Pfizer and BOLT Inter-national; has been a consultant for Pfizer Inc., Janssen, KLJ Associates, Easton Associates, Harvard University, inThought, INC Research, Inc., University of California, Los Angeles, Alzheimer{\textquoteright}s Drug Discovery Foundation and Sanofi-Aventis Groupe; has received funding for travel from Pfizer, AD PD meeting, Paul Sabatier University, Novartis, Tohoku University, MCI Group, France, Travel eDreams, Inc., Neuroscience School of Advanced Studies (NSAS), Danone Trading, BV, CTAD ANT Congres; serves as an associate editor of Alzheimer{\textquoteright}s & Dementia; has received honoraria from Pfizer, Tohoku University, and Danone Trading, BV; has research support from Merck, Avid, DOD and VA; and has stock options in Synarc and Elan.",
year = "2014",
month = may,
doi = "10.1093/brain/awu043",
language = "English (US)",
volume = "137",
pages = "1550--1561",
journal = "Brain",
issn = "0006-8950",
publisher = "Oxford University Press",
number = "5",
}