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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;77:1619–1628

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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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Journal ArticleDOI

Amyloid imaging in aging and dementia: testing the amyloid hypothesis in vivo

TL;DR: Current amyloid imaging techniques, focusing on positron emission tomography with Pittsburgh Compound-B (11C-PIB), are surveyed, finding that PIB binds specifically to fibrillar beta-amyloid deposits, and is a sensitive marker for Aβ pathology in cognitively normal older individuals and patients with mild cognitive impairment and Alzheimer's disease.
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CSF Biomarkers in Prediction of Cerebral and Clinical Change in Mild Cognitive Impairment and Alzheimer's Disease

TL;DR: Results indicate that morphometric changes in MCI and AD are not secondary to CSF biomarker changes and that the two types of biomarkers yield complementary information.
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CSF biomarkers and medial temporal lobe atrophy predict dementia in mild cognitive impairment.

TL;DR: Findings suggest an added value of CSF to MRI in the diagnostic work up of patients presenting at a memory clinic and a fourfold higher risk was found for patients with both abnormal CSF biomarkers and MTA compared to patients with either test abnormal.
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Fully-Automated Quantification of Regional Brain Volumes for Improved Detection of Focal Atrophy in Alzheimer Disease

TL;DR: Tests of a fully automated MR imaging postprocessing system for volumetric analysis of structures known to be affected in early Alzheimer disease yielded results that correlated highly with independent computer-aided manual segmentation and were sensitive to the anatomic atrophy characteristic of mild AD.
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A single ascending dose study of bapineuzumab in patients with Alzheimer disease.

TL;DR: This small, single-dose study demonstrated the safety profile and PK characteristics of bapineuzumab and was used to design later safety and efficacy trials.
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