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Predicting MCI outcome with clinically available MRI and CSF biomarkers

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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The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging and Alzheimer's Association workgroup

TL;DR: Criteria for the symptomatic predementia phase of Alzheimer’s disease (AD), referred to in this article as mild cognitive impairment due to AD, has four levels of certainty, depending on the presence and nature of the biomarker findings.
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Cerebrospinal fluid tau and ptau181 increase with cortical amyloid deposition in cognitively normal individuals: Implications for future clinical trials of Alzheimer's disease

TL;DR: This work reports a positive linear relationship between CSF tau/ptau181 (primary constituents of neurofibrillary tangles) with the amount of cortical amyloid and observes a strong inverse relationship of cortical PIB binding with CSF Aβ42 but not for plasma Aβ species.
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Alzheimer Disease: Quantitative Structural Neuroimaging for Detection and Prediction of Clinical and Structural Changes in Mild Cognitive Impairment

TL;DR: Semiautomated, individually specific quantitative MR imaging methods can be used to identify a pattern of regional atrophy in MCI that is predictive of clinical decline and structural loss that may aid in prediction of patient prognosis and increase the efficiency of clinical trials.
Journal ArticleDOI

Cognitive Decline and Brain Volume Loss as Signatures of Cerebral Amyloid-β Peptide Deposition Identified With Pittsburgh Compound B: Cognitive Decline Associated With Aβ Deposition

TL;DR: The in vivo measure of cerebral amyloidosis known as [(11)C]PiB is associated with cross-sectional regionally specific brain atrophy and longitudinal cognitive decline in multiple cognitive domains that occur before the clinical diagnosis of Alzheimer disease.
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