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      Neuroimaging and Other Biomarkers for Alzheimer's Disease: The Changing Landscape of Early Detection

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      Annual Review of Clinical Psychology

      Annual Reviews

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          Abstract

          The goal of this review is to provide an overview of biomarkers for Alzheimer's disease (AD), with emphasis on neuroimaging and cerebrospinal fluid (CSF) biomarkers. We first review biomarker changes in patients with late-onset AD, including findings from studies using structural and functional magnetic resonance imaging (MRI), advanced MRI techniques (diffusion tensor imaging, magnetic resonance spectroscopy, perfusion), positron emission tomography with fluorodeoxyglucose, amyloid tracers, and other neurochemical tracers, and CSF protein levels. Next, we evaluate findings from these biomarkers in preclinical and prodromal stages of AD including mild cognitive impairment (MCI) and pre-MCI conditions conferring elevated risk. We then discuss related findings in patients with dominantly inherited AD. We conclude with a discussion of the current theoretical framework for the role of biomarkers in AD and emergent directions for AD biomarker research.

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          Most cited references 155

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          The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease.

          The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia. Copyright © 2011. Published by Elsevier Inc.
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            Cortical surface-based analysis. I. Segmentation and surface reconstruction.

            Several properties of the cerebral cortex, including its columnar and laminar organization, as well as the topographic organization of cortical areas, can only be properly understood in the context of the intrinsic two-dimensional structure of the cortical surface. In order to study such cortical properties in humans, it is necessary to obtain an accurate and explicit representation of the cortical surface in individual subjects. Here we describe a set of automated procedures for obtaining accurate reconstructions of the cortical surface, which have been applied to data from more than 100 subjects, requiring little or no manual intervention. Automated routines for unfolding and flattening the cortical surface are described in a companion paper. These procedures allow for the routine use of cortical surface-based analysis and visualization methods in functional brain imaging. Copyright 1999 Academic Press.
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              The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease.

              The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of developing criteria for the symptomatic predementia phase of Alzheimer's disease (AD), referred to in this article as mild cognitive impairment due to AD. The workgroup developed the following two sets of criteria: (1) core clinical criteria that could be used by healthcare providers without access to advanced imaging techniques or cerebrospinal fluid analysis, and (2) research criteria that could be used in clinical research settings, including clinical trials. The second set of criteria incorporate the use of biomarkers based on imaging and cerebrospinal fluid measures. The final set of criteria for mild cognitive impairment due to AD has four levels of certainty, depending on the presence and nature of the biomarker findings. Considerable work is needed to validate the criteria that use biomarkers and to standardize biomarker analysis for use in community settings. Copyright © 2011 The Alzheimer's Association. All rights reserved.
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                Author and article information

                Journal
                Annual Review of Clinical Psychology
                Annu. Rev. Clin. Psychol.
                Annual Reviews
                1548-5943
                1548-5951
                March 28 2013
                March 28 2013
                : 9
                : 1
                : 621-648
                Affiliations
                [1 ]Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana 46202; email: ,
                Article
                10.1146/annurev-clinpsy-050212-185535
                3955298
                23297785
                © 2013

                Neurology, Health & Social care, Clinical Psychology & Psychiatry, Public health

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