Abstract
Clinical trials of cholinesterase inhibitor (ChEI) drugs, although generally reporting only minimal improvements in patients with Alzheimers disease (AD), indicate that a subgroup of patients may respond substantially to treatment. This study aimed to assess the clinically variable ChEI treatment effects in a group of patients with mild AD using a semantic association and an N-back light working memory activation paradigm. Twenty-six patients with probable mild AD treated with a ChEI for 20 weeks were retrospectively divided into responders and non-responders. Patients were classified as responders if their Clinicians Interview Based Impression of Change (CIBIC - Plus) score was four or less and if they had an increase of at least two points on the MMSE. These criteria resulted in two subgroups comprising nine responders and seventeen non responders. Nine healthy elderly age-matched controls were also recruited as a comparison group. ChEI treatment was accompanied by significant modulation of task induced activation increases in both fMRI tasks in AD responders. The effect of ChEI response was in effect a restoration of regional brain function in the same areas used by elderly controls when performing these tasks. In non-responders decrements in task related activation were observed and over time activation patterns appeared less like the elderly controls. Screening semantic fluency scores correlated negatively with activation increases at retest. In the paper, a tentative explanation is offered of why subgroups of patients with a similar clinical diagnosis and level of clinical severity show a different physiological response to ChE inhibition.
Keywords: Alzheimer's disease, response, treatment, fMRI, ChEI, dementia
Current Alzheimer Research
Title: Responders to ChEI Treatment of Alzheimers Disease Show Restitution of Normal Regional Cortical Activation
Volume: 6 Issue: 2
Author(s): Annalena Venneri, William J. McGeown and Michael F. Shanks
Affiliation:
Keywords: Alzheimer's disease, response, treatment, fMRI, ChEI, dementia
Abstract: Clinical trials of cholinesterase inhibitor (ChEI) drugs, although generally reporting only minimal improvements in patients with Alzheimers disease (AD), indicate that a subgroup of patients may respond substantially to treatment. This study aimed to assess the clinically variable ChEI treatment effects in a group of patients with mild AD using a semantic association and an N-back light working memory activation paradigm. Twenty-six patients with probable mild AD treated with a ChEI for 20 weeks were retrospectively divided into responders and non-responders. Patients were classified as responders if their Clinicians Interview Based Impression of Change (CIBIC - Plus) score was four or less and if they had an increase of at least two points on the MMSE. These criteria resulted in two subgroups comprising nine responders and seventeen non responders. Nine healthy elderly age-matched controls were also recruited as a comparison group. ChEI treatment was accompanied by significant modulation of task induced activation increases in both fMRI tasks in AD responders. The effect of ChEI response was in effect a restoration of regional brain function in the same areas used by elderly controls when performing these tasks. In non-responders decrements in task related activation were observed and over time activation patterns appeared less like the elderly controls. Screening semantic fluency scores correlated negatively with activation increases at retest. In the paper, a tentative explanation is offered of why subgroups of patients with a similar clinical diagnosis and level of clinical severity show a different physiological response to ChE inhibition.
Export Options
About this article
Cite this article as:
Venneri Annalena, McGeown J. William and Shanks F. Michael, Responders to ChEI Treatment of Alzheimers Disease Show Restitution of Normal Regional Cortical Activation, Current Alzheimer Research 2009; 6 (2) . https://dx.doi.org/10.2174/156720509787602933
DOI https://dx.doi.org/10.2174/156720509787602933 |
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
-
<i>In Vivo/Ex Vivo</i> EPR Investigation of the Brain Redox Status and Blood-Brain Barrier Integrity in the 5xFAD Mouse Model of Alzheimer's Disease
Current Alzheimer Research The Nrf2-ARE Pathway: A Valuable Therapeutic Target for the Treatment of Neurodegenerative Diseases
Recent Patents on CNS Drug Discovery (Discontinued) An Insight in Pathophysiological Mechanism of Alzheimer’s Disease and its Management Using Plant Natural Products
Mini-Reviews in Medicinal Chemistry Low Plasma Leptin in Cognitively Impaired ADNI Subjects: Gender Differences and Diagnostic and Therapeutic Potential
Current Alzheimer Research Bioorganic Compounds Produced by the Fungus Monascus and their Use in Health Sciences and Medicine
Mini-Reviews in Organic Chemistry The Intracellular Domain of Amyloid Precursor Protein is a Potential Therapeutic Target in Alzheimer’s Disease
Current Drug Discovery Technologies Comparative Evaluation of Ethanolic Extracts of Bacopa monnieri, Evolvulus alsinoides, Tinospora cordifolia and their Combinations on Cognitive Functions in Rats
Current Aging Science Graphical Abstracts
Letters in Drug Design & Discovery Age-related Changes in Respiratory Function and Daily Living. A Tentative Model Including Psychosocial Variables, Respiratory Diseases and Cognition
Current Aging Science Glucocorticoids, the Etiology of Obesity and the Metabolic Syndrome
Current Alzheimer Research KRAB-Zinc Finger Proteins: A Repressor Family Displaying Multiple Biological Functions
Current Genomics Pleasure as an Overlooked Target of Substance Use Disorder Research and Treatment
Current Drug Abuse Reviews WITHDRAWN: MicroRNA-125b can Target p38MAPK to Resolve Intermittent Hypoxia- Induced Dementia in Murine Models
Current Neurovascular Research Appraisal of AβPP Transgenic Mice as Models for Alzheimers Disease Amyloid Cascade
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Anti-Alzheimer Therapeutic Drugs Targeting γ-Secretase
Current Topics in Medicinal Chemistry A Speech Recognition-based Solution for the Automatic Detection of Mild Cognitive Impairment from Spontaneous Speech
Current Alzheimer Research A Review: Natural Compounds as Anti-Alzheimer´s Disease Agents
Current Nutrition & Food Science Tryptamine Induces Axonopathy and Mitochondriopathy Mimicking Neurodegenerative Diseases via Tryptophanyl-tRNA Deficiency
Current Alzheimer Research Reduction in Ischemic Cerebral Infarction is Mediated through Golgi Phosphoprotein 3 and Akt/mTOR Signaling Following Salvianolate Administration
Current Neurovascular Research Epigenetics in the Cerebrovascular System: Changing the Code without Altering the Sequence
Current Neurovascular Research