Abstract
Background: Combining optimized cognitive (Alzheimer's Disease Assessment Scale- Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer's disease for tracking progression in clinical trials may provide greater sensitivity than currently used methods, which have yielded negative results in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcomponents yielded by cognitive and imaging testing, to address the symptomatic and anatomical variability of Alzheimer's disease.
Method: Using latent variable analysis, we thoroughly investigated the relationship between cognitive impairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer's clinical trials that combines cognitive and atrophy markers.
Results: Atrophy within specific brain regions was found to be closely related with impairment in cognitive domains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivity in tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and a real world problem. The biomarker also improved the selection of MCI patients (78.8±4.9% specificity at 80% sensitivity) that will evolve to Alzheimer's disease for clinical trials.
Conclusion: The proposed biomarker provides a boost to the efficacy of clinical trials focused in the mild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatment effects and improving the selection of MCI patients that will evolve to Alzheimer’s disease.
Keywords: Latent variable modeling, Alzheimer's disease assessment scale, Alzheimer's clinical trial, cerebral atrophy, cognitive impairment, mild cognitive impairment.
Current Alzheimer Research
Title:A Biomarker Combining Imaging and Neuropsychological Assessment for Tracking Early Alzheimer's Disease in Clinical Trials
Volume: 15 Issue: 5
Author(s): Nishant Verma, S. Natasha Beretvas, Belen Pascual, Joseph C. Masdeu, Mia K. Markey* The Alzheimer's Disease Neuroimaging Initiative
Affiliation:
- Department of Biomedical Engineering, The University of Texas at Austin, 107 W. Dean Keeton Street Stop C0800, Austin, TX 78712,United States
Keywords: Latent variable modeling, Alzheimer's disease assessment scale, Alzheimer's clinical trial, cerebral atrophy, cognitive impairment, mild cognitive impairment.
Abstract: Background: Combining optimized cognitive (Alzheimer's Disease Assessment Scale- Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer's disease for tracking progression in clinical trials may provide greater sensitivity than currently used methods, which have yielded negative results in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcomponents yielded by cognitive and imaging testing, to address the symptomatic and anatomical variability of Alzheimer's disease.
Method: Using latent variable analysis, we thoroughly investigated the relationship between cognitive impairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer's clinical trials that combines cognitive and atrophy markers.
Results: Atrophy within specific brain regions was found to be closely related with impairment in cognitive domains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivity in tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and a real world problem. The biomarker also improved the selection of MCI patients (78.8±4.9% specificity at 80% sensitivity) that will evolve to Alzheimer's disease for clinical trials.
Conclusion: The proposed biomarker provides a boost to the efficacy of clinical trials focused in the mild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatment effects and improving the selection of MCI patients that will evolve to Alzheimer’s disease.
Export Options
About this article
Cite this article as:
Verma Nishant , Beretvas Natasha S. , Pascual Belen , Masdeu C. Joseph , Markey K. Mia *, The Alzheimer's Disease Neuroimaging Initiative , A Biomarker Combining Imaging and Neuropsychological Assessment for Tracking Early Alzheimer's Disease in Clinical Trials, Current Alzheimer Research 2018; 15 (5) . https://dx.doi.org/10.2174/1567205014666171106150309
DOI https://dx.doi.org/10.2174/1567205014666171106150309 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Is the Deficiency of Vitamin B12 Related to Oxidative Stress and Neurotoxicity in Parkinsons Patients?
CNS & Neurological Disorders - Drug Targets Progress and Promise of Nur77-based Therapeutics for Central Nervous System Disorders
Current Neuropharmacology Association of Prolyl Oligopeptidase with Conventional Neurotransmitters in the Brain
CNS & Neurological Disorders - Drug Targets Breathing Generation and Potential Pharmacotherapeutic Approaches to Central Respiratory Disorders
Current Medicinal Chemistry Cognitive Dysfunction in Major Depressive Disorder: A State-of-the-Art Clinical Review
CNS & Neurological Disorders - Drug Targets Harmaline and its Derivatives Against the Infectious Multi-Drug Resistant Escherichia coli
Medicinal Chemistry Responders to ChEI Treatment of Alzheimers Disease Show Restitution of Normal Regional Cortical Activation
Current Alzheimer Research The Role of Genes (and Environmental Stress) in Depression: An Update
Current Psychiatry Reviews Patient Variables Associated with the Assignment of a Formal Dementia Diagnosis to Positively Screened Primary Care Patients
Current Alzheimer Research Therapeutic Potential of γ -Secretase Inhibitors and Modulators
Current Topics in Medicinal Chemistry Fetzima (levomilnacipran), a Drug for Major Depressive Disorder as a Dual Inhibitor for Human Serotonin Transporters and Beta-Site Amyloid Precursor Protein Cleaving Enzyme-1
CNS & Neurological Disorders - Drug Targets Potential for Stem Cells Therapy in Alzheimer’s Disease: Do Neurotrophic Factors Play Critical Role?
Current Alzheimer Research Editorial [Hot topic: Cognitive Enhancing Drugs: A Blessing for Society? (Joris C. Verster)]
Current Drug Abuse Reviews Val17Ile Single Nucleotide Polymorphisms Similarly as Ala15Thr Could be Related to the Lower Secretory Dynamics of PAI-1 Secretion – Theoretical Evidence
Current Molecular Medicine Oxidative Stress Mechanisms and Potential Therapeutic Modalities in Alzheimer Disease
Medicinal Chemistry Reviews - Online (Discontinued) Is VEGF a Key Target of Cotinine and Other Potential Therapies Against Alzheimer Disease?
Current Alzheimer Research Evaluation of Blood Pressure Control using a New Arterial Stiffness Parameter, Cardio-ankle Vascular Index (CAVI)
Current Hypertension Reviews Pathophysiology of Atherosclerosis: The Role of Inflammation
Current Pharmaceutical Design Synthesis of Highly Functionalised Dispiropyrrolidine Derivatives as Novel Acetylcholinesterase Inhibitors
Letters in Drug Design & Discovery Older Australians: Structural barriers to learning in later life
Current Aging Science