Abstract
Background: The Alzheimer's Disease Neuroimaging Initiative (ADNI) was created to develop standards for brain imaging and biomarkers for diagnosis and treatment trials. Using the ADNI dataset, experts have found that low cerebrospinal fluid amyloid-β1-42 (CSF Aβ1-42) concentration and high total-tau/Aβ1-42 ratio are highly predictive of progression in amnestic mild cognitive impairment (aMCI), and recommended these biomarkers to support the diagnosis of prodromal Alzheimer’s disease and select patients for clinical trials. However, biomarker selection criteria may introduce systematic bias that undermines their utility.
Methods: We tested for systematic biases among individuals undergoing lumbar puncture in the ADNI dataset who fulfilled the following entry criteria: (1) aMCI with CSF Aβ1-42 ≤ 192 pG/mL, compared to aMCI with Aβ1-42 > 192 pG/mL, and (2) aMCI with total-tau/Aβ1-42 > 0.39, compared to aMCI with total-tau/Aβ1-42 ≤ 0.39, as well as comparisons between participants with aMCI with and without lumbar puncture.
Findings: Individuals with low CSF Aβ1-42 scored significantly poorer than individuals with high Aβ1-42 on several baseline measures of disease severity, including Logical Memory II (3.24 vs 4.73; p<0.001), Functional Activities Questionnaire (4.30 vs 2.37; p<0.001), and Alzheimer's Disease Assessment Scale-cognitive (12.23 vs 10.09; p=0.002). Similar results were found using high total-tau/Aβ1-42. No differences were found for individuals with and without lumbar puncture except for marital status.
Interpretations: Individuals with aMCI with low Aβ1-42 in the ADNI dataset appear to have more advanced disease than those with high Aβ1-42. Selection criteria based on ADNI, as well as design of future studies, must account for potential confounds between biomarker status and disease severity to ensure that the former, and not the latter, is the true determinant of predictive accuracy.
Keywords: ADNI, Alzheimer’s disease, amyloid, biomarker, clinical trials, confounding, prediction, Neuroimaging Initiative, ApoE genotyping
Current Alzheimer Research
Title:Biomarker Positive and Negative Subjects in the ADNI Cohort: Clinical Characterization
Volume: 9 Issue: 10
Keywords: ADNI, Alzheimer’s disease, amyloid, biomarker, clinical trials, confounding, prediction, Neuroimaging Initiative, ApoE genotyping
Abstract: Background: The Alzheimer's Disease Neuroimaging Initiative (ADNI) was created to develop standards for brain imaging and biomarkers for diagnosis and treatment trials. Using the ADNI dataset, experts have found that low cerebrospinal fluid amyloid-β1-42 (CSF Aβ1-42) concentration and high total-tau/Aβ1-42 ratio are highly predictive of progression in amnestic mild cognitive impairment (aMCI), and recommended these biomarkers to support the diagnosis of prodromal Alzheimer’s disease and select patients for clinical trials. However, biomarker selection criteria may introduce systematic bias that undermines their utility.
Methods: We tested for systematic biases among individuals undergoing lumbar puncture in the ADNI dataset who fulfilled the following entry criteria: (1) aMCI with CSF Aβ1-42 ≤ 192 pG/mL, compared to aMCI with Aβ1-42 > 192 pG/mL, and (2) aMCI with total-tau/Aβ1-42 > 0.39, compared to aMCI with total-tau/Aβ1-42 ≤ 0.39, as well as comparisons between participants with aMCI with and without lumbar puncture.
Findings: Individuals with low CSF Aβ1-42 scored significantly poorer than individuals with high Aβ1-42 on several baseline measures of disease severity, including Logical Memory II (3.24 vs 4.73; p<0.001), Functional Activities Questionnaire (4.30 vs 2.37; p<0.001), and Alzheimer's Disease Assessment Scale-cognitive (12.23 vs 10.09; p=0.002). Similar results were found using high total-tau/Aβ1-42. No differences were found for individuals with and without lumbar puncture except for marital status.
Interpretations: Individuals with aMCI with low Aβ1-42 in the ADNI dataset appear to have more advanced disease than those with high Aβ1-42. Selection criteria based on ADNI, as well as design of future studies, must account for potential confounds between biomarker status and disease severity to ensure that the former, and not the latter, is the true determinant of predictive accuracy.
Export Options
About this article
Cite this article as:
Biomarker Positive and Negative Subjects in the ADNI Cohort: Clinical Characterization, Current Alzheimer Research 2012; 9 (10) . https://dx.doi.org/10.2174/156720512804142976
DOI https://dx.doi.org/10.2174/156720512804142976 |
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
-
Central Nervous System Acting Drugs in Treatment of Migraine Headache
Central Nervous System Agents in Medicinal Chemistry Dual Cross-Talk between Nitric Oxide and D-Serine in Astrocytes and Neurons in the Brain
Central Nervous System Agents in Medicinal Chemistry Matter of Life and Death: the Pharmacological Approaches Targeting Apoptosis in Brain Diseases
Current Pharmaceutical Design Motor and Anxiety Effects of PNU-282987, An Alpha7 Nicotinic Receptor Agonist, and Stress in an Animal Model of Alzheimer’s Disease
Current Alzheimer Research Von Willebrand Factor and Thrombosis: Risk Factor, Actor and Pharmacological Target
Current Vascular Pharmacology Diffusion Tensor Imaging in Alzheimers Disease
Current Medical Imaging Control of Neuropathic Pain by Immune Cells and Opioids
CNS & Neurological Disorders - Drug Targets The Metabotropic Glutamate Receptor System: G-Protein Mediated Pathways that Modulate Neuronal and Vascular Cellular Injury
Current Medicinal Chemistry - Central Nervous System Agents Crystal Structure and Interaction of Phycocyanin with β-Secretase: A Putative Therapy for Alzheimer's Disease
CNS & Neurological Disorders - Drug Targets Telmisartan Promotes Potential Glucose Homeostasis in Stroke-Resistant Spontaneously Hypertensive Rats via Peroxisome Proliferator-Activated Receptor γ Activation
Current Neurovascular Research University of Kentucky Sanders-Brown Healthy Brain Aging Volunteers: Donor Characteristics, Procedures and Neuropathology
Current Alzheimer Research Cortical and Putamen Age-Related Changes in the Microvessel Density and Astrocyte Deficiency in Spontaneously Hypertensive and Stroke-Prone Spontaneously Hypertensive Rats
Current Neurovascular Research RAGE: A Multi-Ligand Receptor Unveiling Novel Insights in Health and Disease
Current Medicinal Chemistry Adiponectin: Merely a Bystander or the Missing Link to Cardiovascular Disease?
Current Topics in Medicinal Chemistry Neural Stem Cell Niches in Health and Diseases
Current Pharmaceutical Design Development of a Registry for Down Syndrome in the Gulf Area of the Middle East
Applied Clinical Research, Clinical Trials and Regulatory Affairs Targeting Beta-Amyloid Pathogenesis Through Acetylcholinesterase Inhibitors
Current Pharmaceutical Design Viral Inhibition of Tumour Necrosis Factor-α (TNFα) and TNF-Receptor Induced Apoptosis and Inflammation
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Running Exercise Reduces Myelinated Fiber Loss in the Dentate Gyrus of the Hippocampus in APP/PS1 Transgenic Mice
Current Alzheimer Research Mitochondrial Aconitase in Neurodegenerative Disorders: Role of a Metabolism- related Molecule in Neurodegeneration
Current Drug Targets