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Prediction of Amyloidosis from Neuropsychological and MRI Data for Cost Effective Inclusion of Pre-symptomatic Subjects in Clinical Trials [chapter]

Manon Ansart, Stéphane Epelbaum, Geoffroy Gagliardi, Olivier Colliot, Didier Dormont, Bruno Dubois, Harald Hampel, Stanley Durrleman
2017 Lecture Notes in Computer Science  
We propose a method for selecting pre-symptomatic subjects likely to have amyloid plaques in the brain, based on the automatic analysis of neuropsychological and MRI data and using a cross-validated binary  ...  By avoiding systematic PET scan for selecting subjects, it reduces the cost of forming cohorts of subjects with amyloid plaques for clinical trials, by scanning fewer subjects but increasing the number  ...  HH is supported by the AXA Research Fund, the Fondation UPMC and the Fondation pour la Recherche sur Alzheimer, Paris, France. OC is supported by a "contrat d'interface local" from AP-HP.  ... 
doi:10.1007/978-3-319-67558-9_41 fatcat:rxb4wwfiyfartbyjokhgz2bffe

Biomarker-based prediction of progression in MCI: comparison of AD signature and hippocampal volume with spinal fluid amyloid-β and tau

Bradford Dickerson
2013 Frontiers in Aging Neuroscience  
Data were obtained from the ADNI-1 (Alzheimer's Disease Neuroimaging Initiative Phase 1) database on all individuals with a baseline diagnosis of MCI, baseline MRI and CSF data, and at least one follow-up  ...  We investigated the utility of magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers in predicting progression from amnesic MCI to dementia, testing the hypotheses that (1) markers  ...  This analysis was also supported by grants from the NIA P50-AG005134, P30AG010124, and the Alzheimer's Association. We thank Michael Brickhouse for his assistance in data management and analysis.  ... 
doi:10.3389/fnagi.2013.00055 pmid:24130528 pmcid:PMC3795312 fatcat:q7a5gd62vbasvde576gmksbjgi

The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement

Michael W. Weiner, Dallas P. Veitch, Paul S. Aisen, Laurel A. Beckett, Nigel J. Cairns, Robert C. Green, Danielle Harvey, Clifford R. Jack, William Jagust, John C. Morris, Ronald C. Petersen, Jennifer Salazar (+4 others)
2017 Alzheimer's & Dementia  
INTRODUCTION- The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials.  ...  DISCUSSION-ADNI-3 will aim to inform AD treatment trials and facilitate development of AD disease-modifying treatments.  ...  ; has served on the editorial advisory boards for Alzheimer's & Dementia and MRI; has received honoraria from NeuroVigil, Inc., Insitut Catala de Neurociencies Aplicades, PMDA/Japanese Ministry of Health  ... 
doi:10.1016/j.jalz.2016.10.006 pmid:27931796 pmcid:PMC5536850 fatcat:sutbyvnlqrhtrbexozepcvsimi

Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers

Giovanni B Frisoni, Marina Boccardi, Frederik Barkhof, Kaj Blennow, Stefano Cappa, Konstantinos Chiotis, Jean-Francois Démonet, Valentina Garibotto, Panteleimon Giannakopoulos, Anton Gietl, Oskar Hansson, Karl Herholz (+36 others)
2017 Lancet Neurology  
combinations of biomarkers; and developing best practice guidelines for the use of biomarkers in qualified memory clinics in the context of phase IV studies.  ...  Priorities included: definition of the assays; reading procedures and thresholds for normality; performance in detecting early disease; accounting for the effect of covariates; diagnostic algorithms comprising  ...  Poor specificity may result in over-diagnosis and cause unnecessary anxiety, over-treatment and inappropriate inclusion in clinical trials, exposing patients to unnecessary side-effects as well as diluting  ... 
doi:10.1016/s1474-4422(17)30159-x pmid:28721928 fatcat:pnefncfctvhulnxqg4rvwsxfwy

Combination of plasma amyloid beta(1-42/1-40) and glial fibrillary acidic protein strongly associates with cerebral amyloid pathology

Inge M. W. Verberk, Elisabeth Thijssen, Jannet Koelewijn, Kimberley Mauroo, Jeroen Vanbrabant, Arno de Wilde, Marissa D. Zwan, Sander C. J. Verfaillie, Rik Ossenkoppele, Frederik Barkhof, Bart N. M. van Berckel, Philip Scheltens (+4 others)
2020 Alzheimer's Research & Therapy  
Background Blood-based biomarkers for Alzheimer's disease (AD) might facilitate identification of participants for clinical trials targeting amyloid beta (Abeta) accumulation, and aid in AD diagnostics  ...  Discussion and conclusions Combination of plasma Abeta(1-42/1-40) and GFAP provides a valuable tool for the identification of amyloid PET status.  ...  Acknowledgements We thank Hans Heijst for his help in performing 723 the plasma biomarker measurements. This research is performed in close col724 laboration with ADx NeuroSciences, Ghent, Belgium.  ... 
doi:10.1186/s13195-020-00682-7 pmid:32988409 fatcat:uuz2ci5txjcklczps4dadkhz5e

Biomarker tests for the diagnosis of Alzheimer's disease: Generating evidence to inform insurance coverage determinations

Steven D. Pearson, Daniel A. Ollendorf, Jennifer A. Colby
2013 Alzheimer's & Dementia  
But it is in the design of these new trials seeking to test AD therapeutics in minimally symptomatic and pre-symptomatic patients that key elements should be considered in order to "build in" the means  ...  Real-world costs of this type will not come from pivotal clinical trials of new therapeutic agents but the data from these trials could be used to create simulation models that can provide estimates of  ... 
doi:10.1016/j.jalz.2013.06.002 pmid:24094912 fatcat:pb3jalwnmvfchoffr4jspvxumi

The critical need for defining preclinical biomarkers in Alzheimer's disease

Massimo S. Fiandaca, Mark E. Mapstone, Amrita K. Cheema, Howard J. Federoff
2014 Alzheimer's & Dementia  
The recent focus on biomarkers for defining the preclinical state of MCI/AD is in the hope of defining a therapeutic window in which the neural substrate remains responsive to treatment.  ...  These failures in treatment efficacy have led many to believe that symptomatic disease, including both mild cognitive impairment (MCI) and AD, may be refractory to therapeutic intervention.  ...  Acknowledgments The authors thank their collaborators at the Georgetown University Medical Center, the University of Rochester School of Medicine, and the University of California at Irvine School of Medicine  ... 
doi:10.1016/j.jalz.2014.04.015 pmid:24924671 fatcat:cixnrb3ylvdyni2jroaiklwbo4

Use of multimodality imaging and artificial intelligence for diagnosis and prognosis of early stages of Alzheimer's disease

Xiaonan Liu, Kewei Chen, Teresa Wu, David Weidman, Fleming Lure, Jing Li
2018 Translational Research: The Journal of Laboratory and Clinical Medicine  
We review the existing work in three sub-areas: diagnosis, prognosis, and methods for handling modality-wise missing data -a commonly encountered problem when using multi-modality imaging for prediction  ...  Factors contributing to missing data include lack of imaging equipment, cost, difficulty of obtaining patient consent, and patient drop off (in longitudinal studies).  ...  The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.  ... 
doi:10.1016/j.trsl.2018.01.001 pmid:29352978 pmcid:PMC5875456 fatcat:o2cljras4fakph536zjys3gybq

Drug development in Alzheimer's disease: the path to 2025

Jeffrey Cummings, Paul S. Aisen, Bruno DuBois, Lutz Frölich, Clifford R. Jack, Roy W. Jones, John C. Morris, Joel Raskin, Sherie A. Dowsett, Philip Scheltens
2016 Alzheimer's Research & Therapy  
from successes and failures; promote data standardization and increase wider data sharing; understand AD at the basic biology level; and rapidly translate new knowledge into clinical development.  ...  There is an opportunity to reduce the time and risk of AD drug development through an improvement in trial design; better trial infrastructure; disease registries of well-characterized participant cohorts  ...  Acknowledgements We thank Bethany Fox for her role in writing the initial outline of this manuscript.  ... 
doi:10.1186/s13195-016-0207-9 pmid:27646601 pmcid:PMC5028936 fatcat:2hcydh3gtrbvrjkxn6uxfi6nhq

Alzheimer's Disease Including Focal Presentations

Nicolas Villain, Bruno Dubois
2019 Seminars in neurology  
This presents a challenge in current clinical practice due to a lack of reliable biomarkers for non-AD neurodegenerative diseases.  ...  Current research criteria focus on biomarkers' status for amyloid and tau using positron emission tomography and cerebrospinal fluid analysis, independent of clinical status.  ...  ACKNOWLEGMENTS The authors would like to thank Corinna Gundelach and Dr Arash Salardini for theirr writing assistance andtheir help in language editing.  ... 
doi:10.1055/s-0039-1681041 fatcat:e73kwd5hdnbijd7ykbeqdutmia

Five-year biomarker progression variability for Alzheimer's disease dementia prediction: Can a complex instrumental activities of daily living marker fill in the gaps?

Ioannis Tarnanas, Anthoula Tsolaki, Mark Wiederhold, Brenda Wiederhold, Magda Tsolaki
2015 Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring  
This has important implications for clinical trials focusing on prevention in asymptomatic individuals.  ...  Methods: A total of 215 subjects were used with a diagnosis of normal, mild cognitive impairment (MCI) or Alzheimer's disease (AD) at baseline.  ...  The authors state that no conflicts of interest exist for this study.  ... 
doi:10.1016/j.dadm.2015.10.005 pmid:27239530 pmcid:PMC4879487 fatcat:vi2hn5nfxrds3omgqngce3aafu

2014 Report on the Milestones for the US National Plan to Address Alzheimer's Disease

Keith N. Fargo, Paul Aisen, Marilyn Albert, Rhoda Au, Maria M. Corrada, Steven DeKosky, David Drachman, Howard Fillit, Laura Gitlin, Magali Haas, Karl Herrup, Claudia Kawas (+28 others)
2014 Alzheimer's & Dementia  
Pursuant to this, the US Department of Health and Human Services (HHS) released the National Plan to Address Alzheimer's Disease in 2012, including an ambitious research goal of preventing and effectively  ...  The workgroup evaluated each milestone and made recommendations to ensure that they collectively constitute an adequate work plan for reaching the goal of preventing and effectively treating Alzheimer's  ...  Milestone F calls for initiation of Phase III trials against at least three known targets, with at least one of these trials in asymptomatic, at risk subjects; and for the inclusion of biomarkers and cognitive  ... 
doi:10.1016/j.jalz.2014.08.103 pmid:25341459 fatcat:vjpraopvtvhw7lisdmpdjgtrnq

Amyloid imaging as a biomarker for cerebral β-amyloidosis and risk prediction for Alzheimer dementia

William E. Klunk
2011 Neurobiology of Aging  
The application of amyloid imaging to screening subjects for trials and use as an outcome measure is discussed in light of longitudinal changes in the in vivo amyloid signal.  ...  Similarities and differences of cerebral amyloid assessment by amyloid imaging and CSF measurements are delineated and an agenda for further research to improve the applicability of amyloid PET to clinical  ...  Acknowledgments Supported by The National Institutes of Health grants: P50 AG005133, R37 AG025516, P01 AG025204.  ... 
doi:10.1016/j.neurobiolaging.2011.09.006 pmid:22078170 pmcid:PMC3233688 fatcat:al4u3hp2prb45hd4i2ryurpppy

Blood-based biomarkers for Alzheimer disease: mapping the road to the clinic

Harald Hampel, Sid E. O'Bryant, José L. Molinuevo, Henrik Zetterberg, Colin L. Masters, Simone Lista, Steven J. Kiddle, Richard Batrla, Kaj Blennow
2018 Nature Reviews Neurology  
Biomarker discovery and development for clinical research, diagnostics and therapy monitoring in clinical trials have advanced rapidly in key areas of medicine - most notably, oncology and cardiovascular  ...  co-development pathway from identification and assay development to validation for clinical use.  ...  He received lecture fees from Biogen and Roche, research grants from Pfizer, Avid, and MSD Avenir (paid to the institution), travel funding from Axovant, Eli Lilly and  ... 
doi:10.1038/s41582-018-0079-7 pmid:30297701 pmcid:PMC6211654 fatcat:m3hvcq2cvzgablmzkzek5chsla

Plasma pTau181 predicts cortical brain atrophy in aging and Alzheimer's disease

Cécile Tissot, for the Alzheimer's Disease Neuroimaging Initiative, Andréa L. Benedet, Joseph Therriault, Tharick A. Pascoal, Firoza Z. Lussier, Paramita Saha-Chaudhuri, Mira Chamoun, Melissa Savard, Sulantha S. Mathotaarachchi, Gleb Bezgin, Yi-Ting Wang (+11 others)
2021 Alzheimer's Research & Therapy  
Methods Observational data was obtained from the Alzheimer's Disease Neuroimaging Initiative, in which participants underwent plasma assessment and magnetic resonance imaging.  ...  Conclusions Higher levels of plasma pTau181 correlate with neurodegeneration and predict further brain atrophy in aging and Alzheimer's disease.  ...  Imaging analyses Pre-processed 1.5-T and 3-T T1-weighted MRI scans were downloaded from the ADNI database (adni.loni.; for pre-processing details, see [10] ).  ... 
doi:10.1186/s13195-021-00802-x pmid:33781319 fatcat:2czzn7vg3jaqzefwufrcej43nu
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