@article{9a3139a8889545a295d73f5bd6d61e6d,
title = "Subtypes based on cerebrospinal fluid and magnetic resonance imaging markers in normal elderly predict cognitive decline",
abstract = "Cerebrospinal fluid (CSF) and structural magnetic resonance imaging (MRI) show patterns of change in Alzheimer's disease (AD) that precede dementia. The Alzheimer's Disease Neuroimaging Initiative (ADNI) studied normal controls (NC), subjects with mild cognitive impairment (MCI), and subjects with AD to identify patterns of biomarkers to aid in early diagnosis and effective treatment of AD. Two hundred twenty-two NC underwent baseline MRI and clinical examination at baseline and at least one follow-up. One hundred twelve also provided CSF at baseline. Unsupervised clustering based on initial CSF and MRI measures was used to identify clusters of participants with similar profiles. Repeated measures regression modeling assessed the relationship of individual measures, and of cluster membership, to cognitive change over 3 years. Most individuals showed little cognitive change. Individual biomarkers had limited predictive value for cognitive decline, but membership in the cluster with the most extreme profile was associated with more rapid decline in ADAS-cog. Subtypes among NC based on multiple biomarkers may represent the earliest stages of subclinical cognitive decline and AD.",
keywords = "Alzheimer's disease, Amyloid beta-protein, Cerebrospinal fluid, Clustering, Cognition, Dementia, Early diagnosis, Hippocampal volume, Normal controls, Structural magnetic resonance imaging, Tau protein",
author = "J. Nettiksimmons and D. Harvey and J. Brewer and O. Carmichael and C. DeCarli and Jack, {C. R.} and R. Petersen and Shaw, {L. M.} and Trojanowski, {J. Q.} and Weiner, {M. W.} and L. Beckett",
note = "Funding Information: Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) ( National Institutes of Health , Grant U01 AG024904 ). ADNI is funded by the 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., and Wyeth, as well as nonprofit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the US Food and Drug Administration. Private sector contributions to ADNI 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, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. 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 , K01 AG030514 , and the Dana Foundation .",
year = "2010",
month = aug,
doi = "10.1016/j.neurobiolaging.2010.04.025",
language = "English (US)",
volume = "31",
pages = "1419--1428",
journal = "Neurobiology of aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
number = "8",
}