Predicting MCI outcome with clinically available MRI and CSF biomarkers
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TLDR
In this paper, 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).Abstract:
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 ® 2011;77:1619–1628read more
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TL;DR: The major accomplishments of ADNI have been the development of standardized methods for clinical tests, magnetic resonance imaging, positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting, and the improvement of clinical trial efficiency through the identification of subjects most likely to undergo imminent future clinical decline and the use of more sensitive outcome measures to reduce sample sizes.
References
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Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease
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Clifford R. Jack,David S. Knopman,William J. Jagust,Leslie M. Shaw,Paul S. Aisen,Michael W. Weiner,Ronald C. Petersen,John Q. Trojanowski +7 more
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TL;DR: The approach taken in ADNI to standardization across sites and platforms of the MRI protocol, postacquisition corrections, and phantom‐based monitoring of all scanners could be used as a model for other multisite trials.
Journal ArticleDOI
Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects.
Leslie M. Shaw,Hugo Vanderstichele,Malgorzata Knapik-Czajka,Christopher M. Clark,Paul S. Aisen,Ronald C. Petersen,Kaj Blennow,Holly Soares,Adam J. Simon,Piotr Lewczuk,Robert A. Dean,Eric Siemers,William Z. Potter,Virginia M.-Y. Lee,John Q. Trojanowski +14 more
TL;DR: Develop a cerebrospinal fluid biomarker signature for mild Alzheimer's disease (AD) in Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects.
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