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;77:1619–1628read more
Citations
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The Alzheimer's Disease Neuroimaging Initiative: a review of papers published since its inception.
Michael W. Weiner,Michael W. Weiner,Dallas P. Veitch,Paul S. Aisen,Laurel A. Beckett,Nigel J. Cairns,Robert C. Green,Danielle J Harvey,Clifford R. Jack,William J. Jagust,Enchi Liu,John C. Morris,Ronald C. Petersen,Andrew J. Saykin,Mark E. Schmidt,Leslie M. Shaw,Judith Siuciak,Holly Soares,Arthur W. Toga,John Q. Trojanowski +19 more
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TL;DR: This study provides Class II evidence that for patients with AD resveratrol is safe, well-tolerated, and alters some AD biomarker trajectories.
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2014 Update of the Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception
Michael W. Weiner,Dallas P. Veitch,Paul S. Aisen,Laurel A. Beckett,Nigel J. Cairns,Jesse M. Cedarbaum,Robert C. Green,Danielle J Harvey,Clifford R. Jack,William J. Jagust,Johan Luthman,John C. Morris,Ronald C. Petersen,Andrew J. Saykin,Leslie M. Shaw,Li Shen,Adam J. Schwarz,Arthur W. Toga,John Q. Trojanowski +18 more
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
Marilyn S. Albert,Steven T. DeKosky,Dennis W. Dickson,Bruno Dubois,Howard Feldman,Nick C. Fox,Anthony Gamst,David Holtzman,William J. Jagust,Ronald C. Petersen,Peter J. Snyder,Maria C. Carrillo,Creighton H. Phelps +12 more
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.
Journal ArticleDOI
Cerebrospinal fluid tau and ptau181 increase with cortical amyloid deposition in cognitively normal individuals: Implications for future clinical trials of Alzheimer's disease
Anne M. Fagan,Mark A. Mintun,Aarti R. Shah,Patricia Aldea,Catherine M. Roe,Robert H. Mach,Daniel S. Marcus,John C. Morris,David M. Holtzman +8 more
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.
Journal ArticleDOI
Alzheimer Disease: Quantitative Structural Neuroimaging for Detection and Prediction of Clinical and Structural Changes in Mild Cognitive Impairment
Linda K. McEvoy,Christine Fennema-Notestine,J. Cooper Roddey,Donald J. Hagler,Dominic Holland,David S. Karow,Christopher J. Pung,James B. Brewer,Anders M. Dale +8 more
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.
Journal ArticleDOI
Qualification of the analytical and clinical performance of CSF biomarker analyses in ADNI
Leslie M. Shaw,Hugo Vanderstichele,Malgorzata Knapik-Czajka,Michal J. Figurski,Els Coart,Kaj Blennow,Holly Soares,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: In this paper, a seven-center inter-laboratory standardization study for cerebrospinal fluid (CSF) total tau (t-tau), phospho-Tau (p-tAU(181), and Aβ(1-42) was conducted as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI).
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