Abstract
It is becoming increasingly clearer that the clinical manifestations of Alzheimers disease (AD) are not only associated with regional grey matter (GM) damage, but also with abnormal integration between cortical brain regions by disconnection mechanism. This concept comes from the evidence that white matter (WM) damage (as assessed by diffusion MR imaging) can be observed in patients with AD since the early clinical stages, and it correlates with clinical measures of cognitive disability. In this perspective, several functional imaging studies, based on PET and resting state fMRI, have provided evidence that brain hypometabolism/disconnection may precede the occurrence of GM atrophy in certain regions of AD brains, such as the cingulate cortex. The cingulum represents the most prominent WM tract of the limbic system, being directly connected to the medial temporal lobe structures. Therefore, this structure likely contributes to changes in functional connectivity observed within the so called default-mode network of AD patients, and its damage is likely to play a remarkable role in the conversion from mild cognitive impairment (MCI) to dementia. Nowadays, the combination of several neuroimaging techniques that provide both, measures of regional GM loss and measures of functional and structural connectivity offer the opportunity to investigate in vivo the pathophysiological changes of brain tissue modifications across the clinical evolution of AD. This paper reviews the main MR based methods of investigation of brain tissue involvement in patients with AD and MCI, and the role they have played in clarifying the differential contribution of GM damage and brain disconnection to AD pathophysiology. This subject seems to be relevant for both, speculative aspects of neurology and application to clinical trials.
Keywords: Alzheimer Disease (AD), Mild Cognitive Impairment (MCI), disconnection, voxel-based morphometry (VBM), tractography, diffusion tensor imaging, MRI
Current Medicinal Chemistry
Title: Regional Grey Matter Loss and Brain Disconnection Across Alzheimer Disease Evolution
Volume: 18 Issue: 16
Author(s): M. Bozzali, A. Padovani, C. Caltagirone and B. Borroni
Affiliation:
Keywords: Alzheimer Disease (AD), Mild Cognitive Impairment (MCI), disconnection, voxel-based morphometry (VBM), tractography, diffusion tensor imaging, MRI
Abstract: It is becoming increasingly clearer that the clinical manifestations of Alzheimers disease (AD) are not only associated with regional grey matter (GM) damage, but also with abnormal integration between cortical brain regions by disconnection mechanism. This concept comes from the evidence that white matter (WM) damage (as assessed by diffusion MR imaging) can be observed in patients with AD since the early clinical stages, and it correlates with clinical measures of cognitive disability. In this perspective, several functional imaging studies, based on PET and resting state fMRI, have provided evidence that brain hypometabolism/disconnection may precede the occurrence of GM atrophy in certain regions of AD brains, such as the cingulate cortex. The cingulum represents the most prominent WM tract of the limbic system, being directly connected to the medial temporal lobe structures. Therefore, this structure likely contributes to changes in functional connectivity observed within the so called default-mode network of AD patients, and its damage is likely to play a remarkable role in the conversion from mild cognitive impairment (MCI) to dementia. Nowadays, the combination of several neuroimaging techniques that provide both, measures of regional GM loss and measures of functional and structural connectivity offer the opportunity to investigate in vivo the pathophysiological changes of brain tissue modifications across the clinical evolution of AD. This paper reviews the main MR based methods of investigation of brain tissue involvement in patients with AD and MCI, and the role they have played in clarifying the differential contribution of GM damage and brain disconnection to AD pathophysiology. This subject seems to be relevant for both, speculative aspects of neurology and application to clinical trials.
Export Options
About this article
Cite this article as:
Bozzali M., Padovani A., Caltagirone C. and Borroni B., Regional Grey Matter Loss and Brain Disconnection Across Alzheimer Disease Evolution, Current Medicinal Chemistry 2011; 18 (16) . https://dx.doi.org/10.2174/092986711795843263
DOI https://dx.doi.org/10.2174/092986711795843263 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Strategies of Functional Foods Promote Sleep in Human Being
Current Signal Transduction Therapy Discovery of Chromen-7-yl Furan-2-Carboxylate as a Potent and Selective Factor XIa Inhibitor
Cardiovascular & Hematological Agents in Medicinal Chemistry Lipid Nanoformulations in the Treatment of Neuropsychiatric Diseases: An Approach to Overcome the Blood Brain Barrier
Current Drug Metabolism Adrenomedullin Expression in Alzheimer's Brain
Current Alzheimer Research Chloride Channels − New Targets for the Prevention of Stroke
Current Vascular Pharmacology Synthesis and Biological Activities of Naturally Functionalized Polyamines: An Overview
Current Medicinal Chemistry Pleiotropic Effects of Drugs Inhibiting the Renin-Angiotensin-Aldosterone System
Current Pharmaceutical Design Properties of Neurotoxic Peptides Related to the Bri Gene
Protein & Peptide Letters SUBJECT INDEX
Current Neuropharmacology Significant Overlapping Modules and Biological Processes Between Stroke and Coronary Heart Disease
CNS & Neurological Disorders - Drug Targets Pneumonia in the Elderly
Current Respiratory Medicine Reviews The Mammalian Tachykinin Ligand-Receptor System: An Emerging Target for Central Neurological Disorders
CNS & Neurological Disorders - Drug Targets Nicotinic Receptors and the Treatment of Attentional and Cognitive Deficits in Neuropsychiatric Disorders: Focus on the α7 Nicotinic Acetylcholine Receptor as a Promising Drug Target for Schizophrenia
Central Nervous System Agents in Medicinal Chemistry Pharmacogenetics and Pharmagenomics, Trends in Normal and Pathological Aging Studies: Focus on p53
Current Pharmaceutical Design AtreMorine Treatment Regulates DNA Methylation in Neurodegenerative Disorders: Epigenetic and Pharmacogenetic Studies
Current Pharmacogenomics and Personalized Medicine On the Possible Relevance of Bottom-up Pathways in the Pathogenesis of Alzheimer’s Disease
Current Topics in Medicinal Chemistry Discovery of Anti-Alzheimer Agents: Current Ligand-Based Approaches toward the Design of Acetylcholinesterase Inhibitors
Mini-Reviews in Medicinal Chemistry Neurological Complications of Anderson-Fabry Disease
Current Pharmaceutical Design Alzheimer Disease and Type 2 Diabetes Mellitus: The Link to Tyrosine Hydroxylase and Probable Nutritional Strategies
CNS & Neurological Disorders - Drug Targets Microbial Agents, Immune Function and Atheromatosis: The Chlamydophila pneumoniae Role
Current Immunology Reviews (Discontinued)