Abstract
Background: Although it is now evident that normal cognition can occur despite significant AD pathology, few studies have attempted to characterize this discordance, or examine factors that may contribute to resilient brain aging in the setting of AD pathology. Methods: More than 2,000 older persons underwent annual evaluation as part of participation in the Religious Orders Study or Rush Memory Aging Project. A total of 966 subjects who had brain autopsy and comprehensive cognitive testing proximate to death were analyzed. Resilience was quantified as a continuous measure using linear regression modeling, where global cognition was entered as a dependent variable and global pathology was an independent variable. Studentized residuals generated from the model represented the discordance between cognition and pathology, and served as measure of resilience. The relation of resilience index to known risk factors for AD and related variables was examined. Results: Multivariate regression models that adjusted for demographic variables revealed significant associations for early life socioeconomic status, reading ability, APOE-ε4 status, and past cognitive activity. A stepwise regression model retained reading level (estimate = 0.10, SE = 0.02; p< 0.0001) and past cognitive activity (estimate = 0.27, SE = 0.09; p = 0.002), suggesting the potential mediating role of these variables for resilience. Conclusions: The construct of resilient brain aging can provide a framework for quantifying the discordance between cognition and pathology, and help identify factors that may mediate this relationship.
Keywords: Cognitive activity, neuropathology, reading level, reserve, resilience.
Current Alzheimer Research
Title:Resilient Brain Aging: Characterization of Discordance between Alzheimer’s Disease Pathology and Cognition
Volume: 10 Issue: 8
Author(s): Selam Negash, Robert S. Wilson, Sue E. Leurgans, David A. Wolk, Julie A. Schneider, Aron S. Buchman, David A. Bennett and Steven. E. Arnold
Affiliation:
Keywords: Cognitive activity, neuropathology, reading level, reserve, resilience.
Abstract: Background: Although it is now evident that normal cognition can occur despite significant AD pathology, few studies have attempted to characterize this discordance, or examine factors that may contribute to resilient brain aging in the setting of AD pathology. Methods: More than 2,000 older persons underwent annual evaluation as part of participation in the Religious Orders Study or Rush Memory Aging Project. A total of 966 subjects who had brain autopsy and comprehensive cognitive testing proximate to death were analyzed. Resilience was quantified as a continuous measure using linear regression modeling, where global cognition was entered as a dependent variable and global pathology was an independent variable. Studentized residuals generated from the model represented the discordance between cognition and pathology, and served as measure of resilience. The relation of resilience index to known risk factors for AD and related variables was examined. Results: Multivariate regression models that adjusted for demographic variables revealed significant associations for early life socioeconomic status, reading ability, APOE-ε4 status, and past cognitive activity. A stepwise regression model retained reading level (estimate = 0.10, SE = 0.02; p< 0.0001) and past cognitive activity (estimate = 0.27, SE = 0.09; p = 0.002), suggesting the potential mediating role of these variables for resilience. Conclusions: The construct of resilient brain aging can provide a framework for quantifying the discordance between cognition and pathology, and help identify factors that may mediate this relationship.
Export Options
About this article
Cite this article as:
Negash Selam, Wilson S. Robert, Leurgans E. Sue, Wolk A. David, Schneider A. Julie, Buchman S. Aron, Bennett A. David and Arnold E. Steven., Resilient Brain Aging: Characterization of Discordance between Alzheimer’s Disease Pathology and Cognition, Current Alzheimer Research 2013; 10 (8) . https://dx.doi.org/10.2174/15672050113109990157
DOI https://dx.doi.org/10.2174/15672050113109990157 |
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
Alzheimer's Disease Drug Development
Alzheimer's disease is a progressive neurodegenerative disorder that affects millions of people worldwide. Despite decades of research, no cure or disease-modifying treatment is available yet. Therefore, the need for developing effective therapies to treat Alzheimer's disease is an urgent matter. This special issue aims to provide a comprehensive overview of ...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
- 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
-
Maternal Fish Oil Supplementation: The Prodrom of Synaptic Protection in Alzheimers Disease
Current Nutrition & Food Science Is there a Possible Single Mediator in Modulating Neuroendocrine–thymus Interaction in Ageing?
Current Aging Science Cholesterol and Alzheimers Disease: Clinical and Experimental Models Suggest Interactions of Different Genetic, Dietary and Environmental Risk Factors
Current Drug Targets Platelet Activating Factor/Platelet Activating Factor Receptor Pathway as a Potential Therapeutic Target in Autoimmune Diseases
Inflammation & Allergy - Drug Targets (Discontinued) Mitochondria, Mitochondrial DNA and Alzheimers Disease. What Comes First?
Current Alzheimer Research Acetylcholinesterase Inhibitors as Disease-Modifying Therapies for Alzheimers Disease
Current Medicinal Chemistry Molecular Mechanisms of Ischemic Neuronal Cell Death - With Relevance to Alzheimers Disease
Current Alzheimer Research New Pharmacological Approaches in Infants with Hypoxic-Ischemic Encephalopathy
Current Pharmaceutical Design Potential Role of Inflammation in Associations between Particulate Matter and Heart Failure
Current Pharmaceutical Design The Axis of Thrombospondin-1, Transforming Growth Factor Beta and Connective Tissue Growth Factor: An Emerging Therapeutic Target in Rheumatoid Arthritis
Current Vascular Pharmacology Polymer-Based Drug Delivery Devices for Neurological Disorders
CNS & Neurological Disorders - Drug Targets Lack of Association Between SLC24A4 Polymorphism and Late-onset Alzheimer's Disease in Han Chinese
Current Neurovascular Research Therapeutic Potential of Janus Kinase 3 (JAK3) Inhibitors
Current Pharmaceutical Design Conference Report: 14th International Congress on Amino Acids, Peptides and Proteins, Vienna, Austria, August 3-7, 2015
CNS & Neurological Disorders - Drug Targets HIV-1, HCV and Alcohol in the CNS: Potential Interactions and Effects on Neuroinflammation
Current HIV Research Clinical Aspects of Melatonin Intervention in Alzheimers Disease Progression
Current Neuropharmacology Editorial [Hot Topic: QSAR Models for Computer-Aided Drug Design and Molecular Docking for Disorders of the Central Nervous System and Other Diseases]
Current Topics in Medicinal Chemistry Interplay between the APOE Genotype and Possible Plasma Biomarkers in Alzheimer’s Disease
Current Alzheimer Research Antidepressants: Update on Benefits and Risks
Current Psychopharmacology Homocysteine and Cerebral Stroke in Developing Countries
Current Medicinal Chemistry