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Imaging Genetics and Biomarker Variations of Clinically Diagnosed Alzheimer's Disease

Imaging Genetics and Biomarker Variations of Clinically Diagnosed Alzheimer's Disease
Author: Edwin Carl Jr Stage
Publisher:
Total Pages: 278
Release: 2020
Genre:
ISBN:

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Neuroimaging biomarkers play a crucial role in our understanding of Alzheimer's disease. Beyond providing a fast and accurate in vivo picture of the neuronal structure and biochemistry, these biomarkers make up a research framework, defined in a 2018 as the A(amyloid)/T(tau)/N(neurodegeneration) framework after three of the hallmarks of Alzheimer's disease. I first used imaging measures of amyloid, tau and neurodegeneration to study clinically diagnosed Alzheimer's disease. After dividing subjects into early (onset younger than 65) and late-onset (onset of 65 and older) amyloid-positive (AD) and amyloid-negative (nonAD) groups, I saw radically differing topographical distribution of tau and neurodegeneration. AD subjects with an early disease onset had a much more severe amyloid, tau and neurodegeneration than lateonset AD. In the nonAD group, neurodegeneration was found only in early-onset FDG PET data and in a nonAlzheimer's-like MRI and FDG pattern for late-onset. The late-onset nonAD resembled that of limbic-predominant age-related TDP-43 encephalopathy. I next utilized an imaging genetics approach to associate genome-wide significant Alzheimer's risk variants to structural (MRI), metabolic (FDG PET) and tau (tau PET) imaging biomarkers. Linear regression was used to select variants for each of the models and included a pooled sample, cognitively normal, mild cognitive impairment and dementia groups in order to fully capture the cognitive spectrum from normal cognition to the most severely impaired. Model selected variants were replicated using voxelwise regression in an exploratory analysis of spatial associations for each modality. For each imaging type, I replicated some associations to the biomarkers previously seen, as well as identified several novel associations. Several variants identified with crucial Alzheimer's biomarkers may be potential future targets for drug interventions.


Biomarkers in Alzheimer's Disease

Biomarkers in Alzheimer's Disease
Author: Tapan Khan
Publisher: Academic Press
Total Pages: 278
Release: 2016-08-02
Genre: Psychology
ISBN: 0128051477

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Biomarkers in Alzheimer’s Disease provides a comprehensive overview of all modalities of Alzheimer’s disease biomarkers, including neuroimaging, cerebrospinal fluid, genomic, and peripheral systems. Each chapter integrates molecular/cellular abnormality due to Alzheimer’s disease and technological advancement of biomarkers techniques. The book is ideal for clinical neuroscience and molecular/cellular neuroscience researchers, psychiatrists, and allied healthcare practitioners involved in the diagnosis and management of patients with cognitive impairment and Alzheimer’s disease, and for differential diagnosis of Alzheimer’s disease with other non-Alzheimer’s dementia. Presents a comprehensive overview detailing all modalities of Alzheimer’s disease biomarkers Written for neuroscience researchers and clinicians studying or treating patients with Alzheimer’s Disease Integrates, in each chapter, the molecular/cellular abnormality due to Alzheimer’s disease and the technological advancement of biomarkers techniques


Imaging and Multiomic Biomarker Applications

Imaging and Multiomic Biomarker Applications
Author: Yongxia Zhou
Publisher: Nova Medicine & Health
Total Pages: 0
Release: 2021-01-20
Genre: Alzheimer's disease
ISBN: 9781536190793

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The well-known Alzheimer's Disease Neuroimaging Initiative (ADNI) Center provides the most advanced, comprehensive, multiparametric and up-to-date biomarkers for mild cognitive impairment (MCI) and early Alzheimer's disease (AD) projects, including neuroimaging, clinical assessments, biospecimens and genetic data. Recent developments in imaging techniques, including new molecular tracers for imaging disease burden and systematic multi-modal integration, have emerged to overcome the limitations of each single modality and individual-dependent variability. The MRI-based high-resolution structural and morphological changes in the brain, such as atrophy, and the abnormal activity/connectivity patterns of the hippocampus subfields and default mode network (DMN) modulation, together with the amyloid and tau neuropathological quantification using PET molecular tracers, could be used to predict brain changes and cognitive performance declines in early AD, including transitional MCI. Finally, a generalized and integrative model with multiple biomarkers could be built to target disease progression and symptom prediction as well as to optimize patient management.Multiomics investigates metabolomic, lipidomic, genomic, transcriptomic and proteomic perspectives by presenting an accurate biochemical profile of the organism in health and disease. The Alzheimer's Disease Metabolomics Consortium (ADMC) in partnership with ADNI is creating a comprehensive biochemical database for patients in the ADNI1 cohort, consisting of eight metabolomics datasets. The vast majorities of biospecimen data provide rich biological information to the human brain at normal and dementia status. One of the purposes is to reveal the connections between disease and multiomics such as obesity, hypertension, cholesterol imbalance and inflammation risks that might lead to neurodegenerative disease. Multiomic biomarker developments in the dementia field have provided earlier clues to novel treatments that help correct metabolic dysfunction and delay disease progression. Furthermore, the assembling of multiomics-based biomarkers including metabolites and lipids, cholesterol biosynthesis, purine metabolism, lipoprotein, bile acids, and genetics as well as their relation to the pathological amyloid and tau network could improve disease diagnosis sensitivity and reveal more diverse and complementary molecular pathways to allow for the advancement of early AD diagnosis and therapeutic prevention. In this book, we report on the significant differences of multiple biomarkers from the ADNI database including neuroimaging, clinical assessments and multiomic biospecimen/genetic data in MCI and early probable AD (pAD), and elucidate the interconnections among different metrics at various domains. Classification results with high accuracies (0.95-1) for each early dementia subtype including early MCI (EMCI), late MCI (LMCI) and pAD, and better prediction of clinical symptoms is achieved with these comprehensive biomarkers. Further longitudinal changes of imaging and neuropsychological biomarkers, and inter-correlations with baseline parameters are examined for a better illustration of disease progression association. Additionally, an analysis of the post-traumatic stress disorder biomarkers is performed with high classification accuracy. With illustrative and rigorous data analyses and confirmative results, this book provides readers with a full spectrum of biomarker research for early dementia diagnosis and treatment, and helps convey the technical development and data evaluation perspectives in advanced medical imaging and various disease application fields.


Imaging in Alzheimer's Disease and Other Dementias, An Issue of Neuroimaging Clinics

Imaging in Alzheimer's Disease and Other Dementias, An Issue of Neuroimaging Clinics
Author: Alison D. Murray
Publisher: Elsevier Health Sciences
Total Pages: 136
Release: 2012-09-14
Genre: Medical
ISBN: 1455742074

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Dementia is a massive and increasing global problem, with the current prevalence anticipated to double every 20 years as people live longer. Neuroimaging in dementia is recommended by most clinical guidelines and its role has traditionally been to exclude a mass lesion, rather than to support a specific diagnosis. All radiologists will be aware of a steady rise in the number of requests for brain imaging in old people, but what can imaging reliably tell us and what kind of imaging should we use? In affluent societies we now have a range of structural and molecular brain imaging techniques at our disposal, with specific ligands and sophisticated image analysis techniques now available for clinical use. However, we have difficulty justifying which patients to scan, using which modality and when. We know that Alzheimer's disease is the most common neuropathology contributing to a diagnosis of Alzheimer's disease but we also know from large post-mortem studies that most brain pathology in those who have died with a diagnosis of dementia is mixed. Thus understanding different diseases that can cause dementia, how these co-exist or interact and appreciating that not all dementia is Alzheimer's disease is important. Equally important is awareness of individual differences in response to a neuropathological burden and what factors provide resilience against dementia that might be maximized to reduce or postpone its impact. This issue draws together contributions from experts in their fields to provide clarity to the topic in a comprehensive collection of articles.


Alzheimer's Disease

Alzheimer's Disease
Author: Harald Hampel
Publisher: Karger Medical and Scientific Publishers
Total Pages: 200
Release: 2012
Genre: Medical
ISBN: 3805598025

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How current biomarkers are modernizing the diagnosis of Alzheimer's disease Expanding knowledge on genetic and epigenetic risk factors is rapidly enhancing our understanding of the complex molecular interactions and systems involved in the pathogenesis of Alzheimer's disease. In this publication, leading experts discuss emerging novel conceptual models of the disease along with advances in the development of surrogate markers that will not only improve the accuracy of diagnostic technologies but also improve the prospects of developing disease-modifying interventions. The novel framework of the disease presented here highlights research on biological markers as well as efforts to validate technologies for early and accurate detection. It also introduces notion of a complex systems dysfunction that extends beyond prevailing ideas derived from the amyloid' or tau' hypotheses. This outstanding publication provides researchers, clinicians, students and other professionals interested in neurodegenerative disorders with a comprehensive update on current trends and future directions in therapy development, with special focus on advances in clinical trial designs.


Biomarkers for Preclinical Alzheimer’s Disease

Biomarkers for Preclinical Alzheimer’s Disease
Author: Robert Perneczky
Publisher: Humana
Total Pages: 272
Release: 2019-03-13
Genre: Medical
ISBN: 9781493992553

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This volume discusses the importance of imaging, fluid, and genetic biomarkers in detecting the earliest pre-symptomatic stages of Alzheimer’s disease (AD). The chapters in this book are separated into five parts. Part one explores the reasons why we need improved approaches for early detection and diagnosis of AD. Part two describes clinical and research techniques for preclinical AD diagnosis. Part three looks at the current methods in use to diagnose AD and how they can also be used for early detection in healthy older individuals. Parts four and five talk about technological advancements in AD diagnosis and ethical considerations in AD research. In Neuromethods series style, chapters include the kind of detail and key advice from the specialists needed to get successful results in your laboratory. Comprehensive and cutting-edge, Biomarkers for Preclinical Alzheimer’s Disease is a valuable resource for individuals interested in the use of biomarker strategies to improve early AD detection. This book will be of great interest to researchers and clinicians from both academia and industry.”


Neuroimaging Markers of Genetic Risk for Alzheimer's Disease in Cognitively Healthy Cohorts

Neuroimaging Markers of Genetic Risk for Alzheimer's Disease in Cognitively Healthy Cohorts
Author: Theresa Maria Harrison
Publisher:
Total Pages: 243
Release: 2016
Genre:
ISBN:

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Drugs developed to slow, halt or reverse the progression of Alzheimer's Disease (AD) have failed to alter the course of the disease in clinical trials. One possible explanation is that drugs need to be administered earlier, before the onset of clinical symptoms. AD-related pathological processes that occur before clinical symptoms emerge define the preclinical phase of the disease. Neuroimaging biomarkers and genetics together present a powerful system for characterizing potential preclinical changes in the brain. The work presented in this volume is predicated on the need for a better understanding of genetic risk and neuroimaging biomarkers for AD in healthy adults. In Chapter 1, a thorough review of neuroimaging genetics in AD is presented. The studies described in Chapters 2 and 3 explore the relationship between functional connectivity and the apolioprotein E (APOE) risk allele, APOE 4. In the first study a pattern of context-dependent connectivity was uncovered that indicates APOE 4 carriers disengage key cortical regions from the hippocampus during a memory task. These findings support the growing consensus that functional connectivity changes may be among the earliest preclinical markers of AD-related changes in the brain. The second study utilized resting state fMRI scans from 570 healthy college-age adults. Young carriers of APOE 4 showed decreased connectivity between key regions involved in AD and increased segregation of task-positive and task-negative regions. This work is a crucial reminder that genetic risk for AD has important implications across the lifespan and that gene-biomarker associations must be tracked over time to identify changes that might be signs of imminent clinical decline. In Chapter 4, the focus expands to include additional genetic risk factors for AD beyond APOE. This study is the first to show that a genetic risk score for AD is significantly associated with hippocampal thinning over two years in a cohort of older, cognitively healthy adults. Finally, Chapter 5 is a call for the further development of polygenic approaches to studying neuroimaging markers of genetic risk for AD. Together, this volume represents steps toward understanding how genetic risk for AD and neuroimaging can be used to identify individuals at greatest risk for decline.


Cerebrospinal Fluid Biomarkers

Cerebrospinal Fluid Biomarkers
Author: Charlotte E. Teunissen
Publisher: Humana
Total Pages: 236
Release: 2022-05-19
Genre: Medical
ISBN: 9781071613214

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This volume covers the latest methods used in clinical neurochemistry laboratories for both clinical practice and research. Chapters in this book discuss topics such as techniques for cerebrospinal fluid (CSF) collection, pre-analytical processing, and basic CSF analysis; an examination of biomarkers including ELISA and automated immunochemical assays for amyloid and tau markers for Alzheimer’s disease; the analysis of neurofilaments by digital ELISA; and an example of successful novel immunoassay development. In the Neuromethods series style, chapters include the kind of detail and key advice from the specialists needed to get successful results in your laboratory. Cutting-edge and thorough, Cerebrospinal Fluid Biomarkers is a valuable resource for clinicians and researchers to use in CSF labs and CSF courses.


Neuroimaging in Dementia

Neuroimaging in Dementia
Author: Frederik Barkhof
Publisher: Springer Science & Business Media
Total Pages: 295
Release: 2011-02-11
Genre: Medical
ISBN: 3642008186

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This up-to-date, superbly illustrated book is a practical guide to the effective use of neuroimaging in the patient with cognitive decline. It sets out the key clinical and imaging features of the various causes of dementia and directs the reader from clinical presentation to neuroimaging and on to an accurate diagnosis whenever possible. After an introductory chapter on the clinical background, the available "toolbox" of structural and functional neuroimaging techniques is reviewed in detail, including CT, MRI and advanced MR techniques, SPECT and PET, and image analysis methods. The imaging findings in normal ageing are then discussed, followed by a series of chapters that carefully present and analyze the key findings in patients with dementias. Throughout, a practical approach is adopted, geared specifically to the needs of clinicians (neurologists, radiologists, psychiatrists, geriatricians) working in the field of dementia, for whom this book will prove an invaluable resource.


Diseases of the Brain, Head and Neck, Spine 2020–2023

Diseases of the Brain, Head and Neck, Spine 2020–2023
Author: Juerg Hodler
Publisher: Springer Nature
Total Pages: 252
Release: 2020-02-14
Genre: Medical
ISBN: 303038490X

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This open access book offers an essential overview of brain, head and neck, and spine imaging. Over the last few years, there have been considerable advances in this area, driven by both clinical and technological developments. Written by leading international experts and teachers, the chapters are disease-oriented and cover all relevant imaging modalities, with a focus on magnetic resonance imaging and computed tomography. The book also includes a synopsis of pediatric imaging. IDKD books are rewritten (not merely updated) every four years, which means they offer a comprehensive review of the state-of-the-art in imaging. The book is clearly structured and features learning objectives, abstracts, subheadings, tables and take-home points, supported by design elements to help readers navigate the text. It will particularly appeal to general radiologists, radiology residents, and interventional radiologists who want to update their diagnostic expertise, as well as clinicians from other specialties who are interested in imaging for their patient care.