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      The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease

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          Abstract

          Introduction

          This study investigated the diagnostic and disease‐monitoring potential of plasma biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and cognitively unimpaired (CU) individuals.

          Methods

          Plasma was analyzed using Simoa assays from 99 CU, 107 MCI, and 103 AD dementia participants.

          Results

          Phosphorylated‐tau181 (P‐tau181), neurofilament light, amyloid‐β (Aβ42/40), Total‐tau and Glial fibrillary acidic protein were altered in AD dementia but P‐tau181 significantly outperformed all biomarkers in differentiating AD dementia from CU (area under the curve [AUC] = 0.91). P‐tau181 was increased in MCI converters compared to non‐converters. Higher P‐tau181 was associated with steeper cognitive decline and gray matter loss in temporal regions. Longitudinal change of P‐tau181 was strongly associated with gray matter loss in the full sample and with Aβ measures in CU individuals.

          Discussion

          P‐tau181 detected AD at MCI and dementia stages and was strongly associated with cognitive decline and gray matter loss. These findings highlight the potential value of plasma P‐tau181 as a non‐invasive and cost‐effective diagnostic and prognostic biomarker in AD.

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          Most cited references63

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          The meaning and use of the area under a receiver operating characteristic (ROC) curve.

          A representation and interpretation of the area under a receiver operating characteristic (ROC) curve obtained by the "rating" method, or by mathematical predictions based on patient characteristics, is presented. It is shown that in such a setting the area represents the probability that a randomly chosen diseased subject is (correctly) rated or ranked with greater suspicion than a randomly chosen non-diseased subject. Moreover, this probability of a correct ranking is the same quantity that is estimated by the already well-studied nonparametric Wilcoxon statistic. These two relationships are exploited to (a) provide rapid closed-form expressions for the approximate magnitude of the sampling variability, i.e., standard error that one uses to accompany the area under a smoothed ROC curve, (b) guide in determining the size of the sample required to provide a sufficiently reliable estimate of this area, and (c) determine how large sample sizes should be to ensure that one can statistically detect differences in the accuracy of diagnostic techniques.
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            A new look at the statistical model identification

            IEEE Transactions on Automatic Control, 19(6), 716-723
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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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                Author and article information

                Contributors
                nicholas.ashton@gu.se
                Journal
                Alzheimers Dement
                Alzheimers Dement
                10.1002/(ISSN)1552-5279
                ALZ
                Alzheimer's & Dementia
                John Wiley and Sons Inc. (Hoboken )
                1552-5260
                1552-5279
                25 January 2021
                July 2021
                : 17
                : 7 ( doiID: 10.1002/alz.v17.7 )
                : 1145-1156
                Affiliations
                [ 1 ] Department of Psychiatry and Neurochemistry The Sahlgrenska Academy at the University of Gothenburg Mölndal Sweden
                [ 2 ] Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Gothenburg Sweden
                [ 3 ] Clinical Memory Research Unit Lund University Malmö Sweden
                [ 4 ] Department of Old Age Psychiatry Institute of Psychiatry, Psychology & Neuroscience, King's College London London UK
                [ 5 ] Translational Neuroimaging Laboratory McGill University Montréal Canada
                [ 6 ] Department of Neurology Skåne University Hospital Lund Sweden
                [ 7 ] Wallenberg Centre for Molecular Medicine Lund University Lund Sweden
                [ 8 ] Wallenberg Centre for Molecular and Translational Medicine University of Gothenburg Gothenburg Sweden
                [ 9 ] Department of Neurodegenerative Disease UCL Queen Square Institute of Neurology London UK
                [ 10 ] Department of Medicine Institute of Gerontology and Geriatrics University of Perugia Perugia Italy
                [ 11 ] CHU Toulouse Toulouse France
                [ 12 ] Aristotle University of Thessaloniki Thessaloniki Greece
                [ 13 ] Medical University of Lodz Lodz Poland
                [ 14 ] Institute of Clinical Medicine University of Eastern Finland Kuopio Finland
                [ 15 ] University of Oxford Oxford UK
                [ 16 ] Centre for Age‐Related Medicine Stavanger University Hospital Stavanger Norway
                [ 17 ] Memory Clinic Skåne University Hospital Malmö Sweden
                [ 18 ] Division of Clinical Geriatrics Department of Neurobiology Care Sciences and Society Karolinska Institute Stockholm Sweden
                [ 19 ] Department of Neuroimaging Centre for Neuroimaging Sciences Psychology and Neuroscience King's College London Institute of Psychiatry London UK
                [ 20 ] UK Dementia Research Institute at UCL London UK
                Author notes
                [*] [* ] Correspondence

                Dr. Nicholas J. Ashton, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

                Email: nicholas.ashton@ 123456gu.se

                [†]

                First authors Joel Simrén and Antoine Leuzy contributed equally to this work.

                [‡]

                Senior authors Henrik Zetterberg and Nicholas J. Ashton contributed equally to this work.

                Article
                ALZ12283
                10.1002/alz.12283
                8359457
                33491853
                591322dd-88b2-47ec-bfed-d32bfedbd3eb
                © 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 28 November 2020
                : 20 July 2020
                : 02 December 2020
                Page count
                Figures: 4, Tables: 1, Pages: 12, Words: 7028
                Funding
                Funded by: Swedish Research Council , doi 10.13039/501100004359;
                Award ID: #2017‐00915
                Funded by: Alzheimer Drug Discovery Foundation (ADDF), USA
                Award ID: #RDAPB‐201809‐2016615
                Funded by: Swedish Alzheimer Foundation
                Award ID: #AF‐742881
                Funded by: Hjärnfonden, Sweden
                Award ID: #FO2017‐0243
                Funded by: Swedish government and the County Councils
                Funded by: ALF‐agreement
                Award ID: #ALFGBG‐715986
                Funded by: European Union Joint Program for Neurodegenerative Disorders
                Award ID: JPND2019‐466‐236
                Funded by: European Research Council , doi 10.13039/100010663;
                Award ID: #681712
                Funded by: Swedish State Support for Clinical Research
                Award ID: #ALFGBG‐720931
                Funded by: Alzheimer Drug Discovery Foundation (ADDF), USA
                Award ID: #201809‐2016862
                Funded by: UK Dementia Research Institute at UCL
                Categories
                Featured Article
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                Custom metadata
                2.0
                July 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.5 mode:remove_FC converted:12.08.2021

                alzheimer's disease,magnetic resonance imaging,phosphorylated tau,plasma biomarkers

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