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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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Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study

TL;DR: The extent of innate immune gene upregulation in AD was modest relative to the robust response apparent in the aged brain, consistent with the emerging idea of a critical involvement of inflammation in the earliest stages, perhaps even in the preclinical stage, of AD.
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Alzheimer’s Disease: Past, Present, and Future

TL;DR: A lineage of work beginning with Alzheimer’s own writings and drawings is reviewed, then jump to the modern era beginning in the 1970s and early 1980s and a sampling of neuropsychological and other contextual work from each ensuing decade is provided.
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2014 Update of the Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception

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

Cerebrospinal fluid and plasma biomarkers in Alzheimer disease.

TL;DR: The rationales behind and the diagnostic performances of the core cerebrospinal fluid biomarkers for AD, namely total tau, phosphorylated tau and the 42 amino acid form of amyloid-β are presented.
Journal ArticleDOI

CSF markers for incipient Alzheimer's disease

TL;DR: The CSF biomarkers total tau protein, phosphorylated tauprotein, and the 42 amino-acid residue form of amyloid-beta may, if put in the right clinical context, prove to have high enough diagnostic accuracy to meet the challenge of identifying incipient AD in patients with MCI.
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