@article{34984c9ba0664d92ba4e53b01e015b1a,
title = "CSF biomarker and PIB-PET-derived beta-amyloid signature predicts metabolic, gray matter, and cognitive changes in nondemented subjects",
abstract = "Beta-amyloid (Aβ) is a histopathological hallmark of Alzheimer's disease dementia, but high levels of Aβ in the brain can also be found in a substantial proportion of nondemented subjects. Here we investigated which 2-year rate of brain and cognitive changes are present in nondemented subjects with high and low Aβ levels, as assessed with cerebrospinal fluid and molecular positron emission tomography (PET)-based biomarkers of Aβ. In subjects with mild cognitive impairment, increased brain Aβ levels were associated with significantly faster cognitive decline, progression of gray matter atrophy within temporal and parietal brain regions, and a trend for a faster decline in parietal Fludeoxyglucose (FDG)-PET metabolism. Changes in gray matter and FDG-PET mediated the association between Aβ and cognitive decline. In contrast, elderly cognitively healthy controls (HC) with high Aβ levels showed only a faster medial temporal lobe and precuneus volume decline compared with HC with low Aβ. In conclusion, the current results suggest not only that both functional and volumetric brain changes are associated with high Aβ years before the onset of dementia but also that HC with substantial Aβ levels show higher Aβ pathology resistance, lack other pathologies that condition neurotoxic effects of Aβ, or accumulated Aβ for a shorter time period.",
keywords = "Aβ, FDG-PET, MCI, PIB-PET",
author = "Michael Ewers and Philip Insel and Jagust, {William J.} and Leslie Shaw and {Trojanowski J}, {John Q.} and Paul Aisen and Petersen, {Ronald C.} and Norbert Schuff and Weiner, {Michael W.}",
note = "Funding Information: Merck, Avid, the National Institutes of Health, the DOD, and the Veterans Affairs to M.W.W; Elan/Wyeth Alzheimer{\textquoteright}s Immunotherapy Program North American Advisory Board, Alzheimer{\textquoteright}s Association, Forest, University of California, Davis, Tel-Aviv University Medical School, Colloquium Paris, Ipsen, Wenner-Gren Foundations, Social Security Administration, Korean Neurological Association, National Institutes of Health, Washington University at St Louis, Banner Alzheimer{\textquoteright}s Institute, Clinical Trials on Alzheimer{\textquoteright}s Disease, Veterans Affairs Central Office, Beijing Institute of Geriatrics, Innogenetics, New York University, NeuroVigil, Inc., CHRU-Hopital Roger Salengro, Siemens, AstraZeneca, Geneva University Hospitals, Lilly, University of California, San Diego—ADNI, Paris University, Institut Catala de Neurociencies Aplicades, University of New Mexico School of Medicine, Ipsen, Clinical Trials on Alzheimer{\textquoteright}s Disease, Pfizer, AD PD meeting, Paul Sabatier University, and Novartis to M.W.W. for travel; Alzheimer{\textquoteright}s Disease Neuroimaging Initiative (National Institutes of Health Grant U01 AG024904) for data collection and sharing; National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., as well as nonprofit partners the Alzheimer{\textquoteright}s Association and Alzheimer{\textquoteright}s Drug Discovery Foundation, with participation from the US Food and Drug Administration to ADNI; Foundation for the National Institutes of Health (www.fnih.org) to ADNI for private sector contributions; National Institutes of Health grants P30 AG010129, K01 AG030514, and the Dana Foundation. Funding Information: Data used in the preparation of this article were obtained from the Alzheimer{\textquoteright}s Disease Neuroimaging Initiative (ADNI) database (www .loni.ucla.edu/ADNI). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. ADNI investigators include (complete listing available at http://www.loni.-ucla.edu/ADNI/Collaboration/ADNI_Manuscript_Citations.pdf). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer{\textquoteright}s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuroimaging at the University of California, Los Angeles. Conflict of Interest : Dr Weiner has been on advisory boards for Lilly, Araclon, and Institut Catala de Neurociencies Aplicades, Gulf War Veterans Illnesses Advisory Committee, VACO, Biogen Idec, Elan/Wyeth Alzheimer{\textquoteright}s Immunotherapy Program North American Advisory Board, Novartis Misfolded Protein Scientific Advisory Board Meeting, Banner Alzheimer{\textquoteright}s Institute Alzheimer{\textquoteright}s Prevention Initiative Advisory Board Meeting, and the Research Advisory Committee on Gulf War Veterans{\textquoteright} Illnesses. He has been a consultant for Elan/Wyeth, Novartis, Forest, Ipsen, Daiichi Sankyo, Inc., Astra Zeneca, Araclon, Medivation/Pfizer, TauRx Therapeutics LTD, Bayer Healthcare, Biogen Idec, Exonhit Therapeutics, SA, Servier, and Synarc. Dr Weiner holds stock options with Synarc and Elan. He has been on the Editorial Advisory Boards of the Journals Alzheimer{\textquoteright}s and Dementia and MRI. He has received Honoraria from American Academy of Neurology, Ipsen, NeuroVigil, Inc., and Insitut Catala de Neuro-ciencies Aplicades. Organizations contributing to the Foundation for National Institutes of Health and thus to the National Institute on Aging funded Alzheimer{\textquoteright}s Disease Neuroimaging Initiative are Abbott, Alzheimer{\textquoteright}s Association, Alzheimer{\textquoteright}s Drug Discovery Foundation, Anonymous Foundation, AstraZeneca, Bayer Healthcare, BioClinica, Inc. (ADNI 2), Bristol-Myers Squibb, Cure Alzheimer{\textquoteright}s Fund, Eisai, Elan, Gene Network Sciences, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson & Johnson, Eli Lilly & Company, Medpace, Merck, Novartis, Pfizer Inc, Roche , Schering Plough, Synarc, and Wyeth.",
year = "2012",
month = sep,
doi = "10.1093/cercor/bhr271",
language = "English (US)",
volume = "22",
pages = "1993--2004",
journal = "Cerebral Cortex",
issn = "1047-3211",
publisher = "Oxford University Press",
number = "9",
}