Neuroinflammation in Vascular Dementia describes the molecular mechanisms that drive this transition to mixed pathology, along with the newer lifestyle and pharmacological approaches that can reduce the incidence of dementia. The book describes the practical aspects of neuroimaging methods, along with novel neuroimaging methods, using MRI, that are becoming important clinically. The author also discusses how the diagnosis of dementias will be greatly aided by biomarkers from neuroimaging, blood and CSF biochemistry and neuropsychological testing in the future. This information will be used in precision medicine to design treatment strategies based on the most likely causes of the disease. Dementia research has undergone dramatic growth driven by current and projected increases in the aging of the population, and thus leading to a larger number of patients with dementia by 2050. Hence, advances in neuroimaging, brain chemistry, and genetics have accelerated our understanding of diseases that lead to cognitive decline.
Key Features
Reviews the clinical aspects and subtypes of dementia Explains molecular pathways involved in brain inflammation Includes the role of CSF and blood in diagnosis Covers established and novel neuroimaging methods Discusses established and developing treatment strategies Identifies future directions, such as machine learning and precision medicine
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Cover image Title page Table of Contents Copyright
Chapter 1. Clinical aspects of diagnosis in dementia
Abstract Introduction Determining the etiology of cognitive decline Neurodegenerative causes of dementia Alzheimer’s disease Vascular causes of dementia Mixed dementia—AD and VCID Normal pressure hydrocephalus References
Chapter 2. Neuroimaging methods
Abstract Historical perspective Discovery of computerized axial tomography Nuclear magnetic resonance spectroscopy and magnetic resonance imaging Basic concepts in nuclear magnetic resonance Diffusion tensor imaging Advanced diffusion techniques: fiber tract connectivity with mean kurtosis and constrained spherical deconvolution Detection of white matter injury References
Chapter 3. Biomarkers in cerebrospinal fluid and blood aid diagnosis of dementia
Abstract Pathologic deposition of misfolded proteins in the brain: amyloid, tau, α-synuclein, TDP-43 Biomarkers for amyloid in cerebrospinal fluid Amyloid and tau Biomarkers in mild cognitive impairment Clinical and biological diagnosis of Alzheimer’s disease Theories of Alzheimer’s disease: amyloid hypothesis Alternative Alzheimer’s disease hypotheses: blood–brain barrier dysfunction Positron emission tomography biomarkers Blood-based biomarkers Selection of biomarkers: cerebrospinal fluid versus blood References
Chapter 4. Classification of subtypes of vascular dementia
Abstract Definitions Major types of vascular disease Midlife hypertension and white matter injury Blood vessels and sites of selective vulnerability Monogenic forms of white matter disease References
Chapter 5. Neuroinflammation
Abstract Classic definition of inflammation Inflammation in chronic hypoxic/ischemic disease Consequences of reduced cerebral blood flow Brain fluid interfaces Extracellular matrix and the matrix metalloproteinases Role of the metalloproteinases in the disruption of the blood–brain barrier Angiogenesis Cytokines References
Chapter 6. Animal models for vascular cognitive impairment
Abstract Introduction Bilateral carotid artery occlusion in rat Hypoxic hypoperfusion in mice Ameroid constrictor bilateral carotid artery stenosis model Spontaneously hypertensive rats White matter injury in SHRSP Blood-brain barrier opening and matrix metalloproteinases in SHRSP Hypoxia in SHRSP Mechanism of white matter injury in SHRSP References
Chapter 7. Molecular pathways
Abstract Introduction Burden of disease in normals Consequences of abnormal proteins in the brain Neurovascular unit Disruption of the neurovascular unit in dementia DCE-MRI in cerebral small vessel disease References
Chapter 8. Mechanisms of white matter injury
Abstract White matter is the major site of pathology in vascular-mediated dementia Myelin disruption in inflammation Glutamate-mediated excitotoxicity Inflammation in small vessel disease of the Binswanger’s type Interaction of proteases, angiogenic factors, and cytokines Bystander demyelination References
Chapter 9. Machine learning and precision medicine
Abstract Introduction Machine learning Approach of clinical medicine to diagnosis Early attempts at improving diagnostic accuracy in dementia NMR spectroscopy as a biomarker Diffusion tensor imaging Computer advances and big data References
Chapter 10. Future directions
Abstract Amyloid reconsidered Advanced magnetic resonance imaging methods Genetic studies on early- and late-onset Alzheimer’s disease Early diagnosis of Alzheimer’s disease with measurement of Alzheimer’s disease proteins in plasma Hypoxia and inflammation augment the amyloid theory of chronic subcortical dementia Insights into pathophysiology of Binswanger’s disease Will treatments aimed at reducing inflammation slow WM injury? Can biomarker-driven precision medicine be integrated into clinical practice? Neurology training in the future References Index
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