Integrated Fluid and Neuroimaging Biomarkers for Alzheimer's Disease Predict Longitudinal Brain Amyloid Accumulation, White Matter Microstructural Changes, and Cognitive Decline in Late-middle-aged Risk-enriched Adults PDF Download
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Author: Annie Marie Racine
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Interventions to delay or prevent the onset of Alzheimer's disease (AD) would dramatically reduce the number of people living with dementia in the future. To reach this goal, it will be critical to identify individuals with preclinical AD, a clinically asymptomatic disease stage that is characterized by accumulation of beta-amyloid aggregates and neurofibrillary tangles in the brain, which are thought to contribute to neuronal injury and structural brain changes. The overarching goal of this dissertation was to better understand relationships between key pathological features of AD during this important preclinical timeframe and to assess the combined power of biomarkers to predict progression along the AD trajectory prior to the onset of clinical impairment. These experiments addressed two major questions: 1) are early indicators of preclinical AD better associated with biomarkers that capture multiple pathologies simultaneously than with a biomarker for a single pathology measured in isolation?; and 2) do longitudinal analyses of pathology and cognitive decline within individuals provide better indications of movement along the AD trajectory compared to cross-sectional models? To address these questions, three Specific Aims assessed relationships between multiple biomarkers and both their cross-sectional and longitudinal associations with brain change. Specifically, analyses were performed to investigate whether biomarkers for amyloid and neural injury predict longitudinal brain amyloid accumulation (Specific Aim 1), white matter microstructural changes (Specific Aim 2), and cognitive decline (Specific Aim 3) in late-middle-aged adults with elevated risk of AD due to parental family history and genetic factors. As hypothesized, measures of co-occurring amyloidosis and neural injury were more commonly associated with disease outcomes than markers of a single pathology, and longitudinal models enabled detection of early pathological and cognitive decline often not possible with cross-sectional approaches. This dissertation provides important contributions to the field by assessing the preclinical phase of AD using a unique cohort of individuals who were middle-aged and cognitively healthy at study entry and who are enriched with risk factors for AD; by investigating an extensive panel of multimodal biomarkers; and by examining longitudinally measured change within individuals in terms of both biomarker levels and cognitive performance.
Author: Annie Marie Racine
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Interventions to delay or prevent the onset of Alzheimer's disease (AD) would dramatically reduce the number of people living with dementia in the future. To reach this goal, it will be critical to identify individuals with preclinical AD, a clinically asymptomatic disease stage that is characterized by accumulation of beta-amyloid aggregates and neurofibrillary tangles in the brain, which are thought to contribute to neuronal injury and structural brain changes. The overarching goal of this dissertation was to better understand relationships between key pathological features of AD during this important preclinical timeframe and to assess the combined power of biomarkers to predict progression along the AD trajectory prior to the onset of clinical impairment. These experiments addressed two major questions: 1) are early indicators of preclinical AD better associated with biomarkers that capture multiple pathologies simultaneously than with a biomarker for a single pathology measured in isolation?; and 2) do longitudinal analyses of pathology and cognitive decline within individuals provide better indications of movement along the AD trajectory compared to cross-sectional models? To address these questions, three Specific Aims assessed relationships between multiple biomarkers and both their cross-sectional and longitudinal associations with brain change. Specifically, analyses were performed to investigate whether biomarkers for amyloid and neural injury predict longitudinal brain amyloid accumulation (Specific Aim 1), white matter microstructural changes (Specific Aim 2), and cognitive decline (Specific Aim 3) in late-middle-aged adults with elevated risk of AD due to parental family history and genetic factors. As hypothesized, measures of co-occurring amyloidosis and neural injury were more commonly associated with disease outcomes than markers of a single pathology, and longitudinal models enabled detection of early pathological and cognitive decline often not possible with cross-sectional approaches. This dissertation provides important contributions to the field by assessing the preclinical phase of AD using a unique cohort of individuals who were middle-aged and cognitively healthy at study entry and who are enriched with risk factors for AD; by investigating an extensive panel of multimodal biomarkers; and by examining longitudinally measured change within individuals in terms of both biomarker levels and cognitive performance.
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 186
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Book Description
Interventions to delay or prevent the onset of Alzheimer’s disease (AD) would dramatically reduce the number of people living with dementia in the future. To reach this goal, it will be critical to identify individuals with preclinical AD, a clinically asymptomatic disease stage that is characterized by accumulation of beta-amyloid aggregates and neurofibrillary tangles in the brain, which are thought to contribute to neuronal injury and structural brain changes. The overarching goal of this dissertation was to better understand relationships between key pathological features of AD during this important preclinical timeframe and to assess the combined power of biomarkers to predict progression along the AD trajectory prior to the onset of clinical impairment. These experiments addressed two major questions: 1) are early indicators of preclinical AD better associated with biomarkers that capture multiple pathologies simultaneously than with a biomarker for a single pathology measured in isolation?; and 2) do longitudinal analyses of pathology and cognitive decline within individuals provide better indications of movement along the AD trajectory compared to cross-sectional models? To address these questions, three Specific Aims assessed relationships between multiple biomarkers and both their cross-sectional and longitudinal associations with brain change. Specifically, analyses were performed to investigate whether biomarkers for amyloid and neural injury predict longitudinal brain amyloid accumulation (Specific Aim 1), white matter microstructural changes (Specific Aim 2), and cognitive decline (Specific Aim 3) in late-middle-aged adults with elevated risk of AD due to parental family history and genetic factors. As hypothesized, measures of co-occurring amyloidosis and neural injury were more commonly associated with disease outcomes than markers of a single pathology, and longitudinal models enabled detection of early pathological and cognitive decline often not possible with cross-sectional approaches. This dissertation provides important contributions to the field by assessing the preclinical phase of AD using a unique cohort of individuals who were middle-aged and cognitively healthy at study entry and who are enriched with risk factors for AD; by investigating an extensive panel of multimodal biomarkers; and by examining longitudinally measured change within individuals in terms of both biomarker levels and cognitive performance.
Author: Tapan Khan
Publisher: Academic Press
ISBN: 0128051477
Category : Psychology
Languages : en
Pages : 278
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Book Description
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
Author: Samuel Barrack
Publisher: iMedPub
ISBN: 1492274429
Category : Health & Fitness
Languages : en
Pages : 134
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Book Description
In view of the growing prevalence of AD worldwide, there is an urgent need for the development of better diagnostic tools and more effective therapeutic interventions. Indeed, much work in this field has been done during last decades. As such, a major goal of current clinical research in AD is to improve early detection of disease and presymptomatic detection of neuronal dysfunction, concurrently with the development of better tools to assess disease progression in this group of disorders. All these putative correlates are commonly referred to as AD-related biomarkers. The ideal biomarker should be easy to quantify and measure, reproducible, not subject to wide variation in the general population and unaffected by co- morbid factors. For evaluation of therapies, a biomarker needs to change linearly with disease progression and closely correlate with established clinico-pathological parameters of the disease. There is growing evidence that the use of biomarkers will increase our ability to better indentify the underlying biology of AD, especially in its early stages. These biomarkers will improve the detection of the patients suitable for research studies and drug trials, and they will contribute to a better management of the disease in the clinical practice. Indeed, much work in this field has been done during last decades. The vast number of important applications, combined with the untamed diversity of already identified biomarkers, show that there is a pressing need to structure the research made on AD biomarkers into a solid, comprehensive and easy to use tool to de deployed in clinical settings. To date there are few publications compiling results on this topic. That is why when I was asked to address this task I accepted inmediately. I am happy to present you a bundle of the best articles published about biomarkers for Alzheimer’s disease in recent times.
Author: Jiu Chen
Publisher: Frontiers Media SA
ISBN: 2832542662
Category : Science
Languages : en
Pages : 358
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Book Description
Subjective cognitive decline (SCD) with self-reported concerns and mild cognitive impairment (MCI) are well-established to be at increased risk of developing Alzheimer’s disease (AD) dementia and a clinical continuum of dementia progression as a spectrum of AD. AD may develop from SCD to MCI (early MCI and late MCI) and eventually to AD. Nevertheless, until recently little was known about their pathophysiology associated with cognitive-behavioral syndrome. Although for researchers, scientists and clinicians, the pathophysiology of AD spectrum is an intriguing issue, delineating it in a clear way is far from easy. Taken together, in-depth understanding of neuroimaging-based pathology behind cognitive impairments across AD spectrum may help to develop new strategy for the early diagnosis and treatment of AD. Neuroimaging has been thought to potentially reveal the pathological mechanisms of AD progression. Individuals across AD spectrum are often associated with anatomical and functional brain alterations and cognitive impairment, most of the pathophysiology will focus primarily on the brain. To investigate brain structures and functions associated with cognition, neuroimaging will be the most appropriate tool.
Author: Robert Perneczky
Publisher: Springer Nature
ISBN: 1071637746
Category : Alzheimer's disease
Languages : en
Pages : 345
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Book Description
Zusammenfassung: This fully updated volume provides an up-to-date and comprehensive overview of the current state of technologies helping to accelerate Alzheimer's disease drug development. Addressing the latest advances in preclinical and clinical research, including new insights into the molecular mechanisms and emerging therapeutic strategies, the book continues by exploring digital biomarkers and advanced neuroimaging analysis which will transform how clinical trials in the Alzheimer's disease field are performed. Written for the highly successful Methods in Molecular Biology series, chapters feature the kind of detailed implementation advice that leads to greater success in the lab or clinic. Authoritative and practical, Biomarkers for Alzheimer's Disease Drug Development, Second Edition seeks to inspire and inform future efforts to develop effective treatments for this devastating disease
Author: Yongxia Zhou
Publisher: Nova Medicine & Health
ISBN: 9781536190793
Category : Alzheimer's disease
Languages : en
Pages : 0
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Book Description
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.
Author: David Libon
Publisher: Oxford University Press, USA
ISBN: 0190634235
Category : Medical
Languages : en
Pages : 505
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Book Description
"Cerebrovascular and Alzheimer disease often occur together, but are usually studied apart. This book offers a timely integrated approach to both diseases. Beginning with a section on epidemiology and neuropsychology, this volume goes on to discuss and explore the neuropathological and neurophysiological mechanisms of these disorders. This book then develops a novel concept of an Alzheimer disease/vascular dementia spectrum. Sections on neuroimaging, as well as treatments and interventions follow. The editors have succeeded in gathering an impressive group of clinicians and scientists, who are well qualified by their achievements and leadership to make important contributions to this new integrated approach to dementing disorders. This important book should have broad appeal to anyone studying or caring for patients with dementing disorders, as it is comprehensive, yet focused on a unitary, complementary and pragmatic approach"--
Author: Cassidy M. Fiford
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
This thesis is an investigation into vascular risk, vascular brain lesions, and age contributions to brain atrophy and cognitive decline in Alzheimer"s disease (AD). Associations of white matter hyperintensities (WMHs) to longitudinal hippocampal atrophy were explored in control, mild cognitive impairment (MCI) and AD participants enrolled in the Alzheimer"s Disease Neuroimaging Initiative (ADNI1). Also using ADNI1 data, I identified differences in longitudinal brain atrophy patterns in younger vs. older AD patients. Blood pressure (BP), cognition and brain atrophy were jointly modelled to see how changes in each variable are correlated in ADNI1 and National Alzheimer"s Coordinating Centre (NACC) participants. The independent associations of microbleeds (MBs), lacunes and WMHs to longitudinal atrophy were also explored in ADNIGo and ADNI2. Lastly, I developed a new protocol for semi-automated WMH segmentation and generated "gold standard" segmentations with which to assess the performance of an automated WMH segmentation algorithm. WMHs were found to associate with hippocampal atrophy in controls and MCI, which survived correction for CSF biomarkers of amyloid and tau, and concurrent brain atrophy. Secondly, I found that younger AD patients have greater extra- hippocampal atrophy, with a prominent posterior atrophy pattern, and faster atrophy rates compared to older AD patients. Greater hippocampal atrophy rates were found in MCI and AD patients with higher baseline systolic BP. In ADNI2 and ADNIGo subjects MB presence and WMH volume were associated with increased longitudinal brain atrophy rate, whilst presence of a lacune was associated with a reduced atrophy rate. Lastly, I showed that the automated WMH segmentation algorithm compares well to the "gold standard", and automated volumes were able to predict cognitive change across disease types. This work extends existing knowledge about how age, vascular risk and brain lesions with a presumed vascular aetiology, link with brain atrophy and cognitive decline in ageing and AD.
Author: Chantel Dana Mayo
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Background: Given that brain pathology precedes clinical symptoms in Alzheimer's disease (AD), identifying pre-symptomatic biomarkers is critical in order to implement symptom-delaying strategies as early as possible. Magnetic resonance imaging (MRI) is an ideal method for detecting early brain changes in Alzheimer's disease, as it is non-invasive, easily repeatable, and widely available. To date, MRI biomarker research has largely focused on neuronal loss in grey matter, but there is a lack of research on white matter and its relationship with cognitive performance. Diffusion tensor imaging (DTI) is a MRI-based technique that is particularly sensitive to microstructural white matter characteristics, making it an ideal method to study white matter changes. Methods: Longitudinal DTI and clinical data from the Alzheimer's Disease Neuroimaging Initiative 2 database were used to examine the 1) within-group microstructural white matter changes in individuals with AD and healthy aging controls at baseline and year one; 2) the between-group microstructural differences in individuals with AD and controls at both time points; and 3) the relationship between white matter and cognitive performance at both time points. Results: 1) Within-group: Tract-based Spatial Statistics reveal that individuals with AD have reduced fractional anisotropy (FA) and increased mean diffusivity (MD) in the corpus callosum; internal and external capsule; corona radiata; posterior thalamic radiations; superior and inferior longitudinal fasciculus; fronto-occipital fasciculus; cingulate gyri; fornix; uncinate fasciculus; tapetum; medial lemniscus; cerebellar and cerebral peduncle; and hippocampal cingulum at year one compared to baseline. Controls also had reduced FA and increased MD at year one compared to baseline, but such changes were less extensive and did not include the hippocampal cingulum. 2) Between-group: Relative to controls, individuals with AD had lower FA and higher MD in the corpus callosum, internal and external capsule; corona radiata; posterior thalamic radiation; superior and inferior longitudinal fasciculus and fronto-occipital fasciculus; cingulate gyri; fornix; uncinate fasciculus; tapetum and hippocampal cingulum. 3) There was a positive relationship between FA and an ADNI- derived memory composite score in individuals with AD. Conclusion: The results revealed that DTI holds potential as an AD biomarker given its sensitivity to detect microstructural white matter characteristics. Longitudinal tracking of brain imaging and AD clinical signs in large cohorts are necessary to further evaluate potential clinical utility.
