Journal
NEUROLOGY
Volume 77, Issue 17, Pages 1619-1628Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e3182343314
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Funding
- NIH [NIA K01AG029218, NINDS K02NS067427, P30 AG010129, K01 AG030514]
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- Scripps Mercy Hospital, San Diego, CA
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Abbott
- AstraZeneca
- Bayer Schering Pharma
- Bristol-Myers Squibb
- Eisai Inc.
- Elan Corporation
- Genentech, Inc.
- GE Healthcare
- GlaxoSmithKline
- Innogenetics
- Johnson Johnson
- Eli Lilly and Co.
- Medpace, Inc.
- Merck and Co., Inc.
- Novartis
- Pfizer Inc
- Roche
- Schering-Plough Corp.
- Synarc, Inc.
- Wyeth
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- US Food and Drug Administration
- Dana Foundation
- NIH/NINDS
- Janssen Alzheimer Immunotherapy
- General Electric Medical Foundation
- NIH (NINDS, NIA)
- Research Council, Sweden
- LUA/ALF
- Vastra Gotalandsregionen, Sweden
- Swedish Alzheimer Foundation
- Stiftelsen for Gamla Tjanarinnor
- King Gustaf V and Queen Victoria Foundation
- Swedish Brain Power project
- Swedish Council for Working Life and Social Research
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Objective: To determine the ability of clinically available volumetric MRI (vMRI) and CSF biomarkers, alone or in combination with a quantitative learning measure, to predict conversion to Alzheimer disease (AD) in patients with mild cognitive impairment (MCI). Methods: We stratified 192 MCI participants into positive and negative risk groups on the basis of 1) degree of learning impairment on the Rey Auditory Verbal Learning Test; 2) medial temporal atrophy, quantified from Food and Drug Administration-approved software for automated vMRI analysis; and 3) CSF biomarker levels. We also stratified participants based on combinations of risk factors. We computed Cox proportional hazards models, controlling for age, to assess 3-year risk of converting to AD as a function of risk group and used Kaplan-Meier analyses to determine median survival times. Results: When risk factors were examined separately, individuals testing positive showed significantly higher risk of converting to AD than individuals testing negative (hazard ratios [HR] 1.8-4.1). The joint presence of any 2 risk factors substantially increased risk, with the combination of greater learning impairment and increased atrophy associated with highest risk (HR 29.0): 85% of patients with both risk factors converted to AD within 3 years, vs 5% of those with neither. The presence of medial temporal atrophy was associated with shortest median dementia-free survival (15 months). Conclusions: Incorporating quantitative assessment of learning ability along with vMRI or CSF biomarkers in the clinical workup of MCI can provide critical information on risk of imminent conversion to AD. Neurology (R) 2011;77:1619-1628
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