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Author: Erika Jane Starks
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Author: Erika Jane Starks
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
Get Book Here
Book Description
Author: Erika Jane Starks
Publisher:
ISBN:
Category :
Languages : en
Pages : 390
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Book Description
Dementia due to Alzheimer’s disease (AD) is a devastating condition characterized clinically by progressive cognitive impairment and pathologically by amyloid plaques, neurofibrillary tangles and severe atrophy. Diabetes mellitus (DM), obesity, and associated insulin resistance in middle age, are linked to a greater risk of developing dementia due to AD. Given the potential of modifying metabolic risk factors at midlife, my research explored the pathophysiological mechanisms involved in the link between insulin resistance and obesity at middle-age and AD pathology using molecular and imaging biomarkers. Specifically, my studies aimed to investigate the potential effect of metabolic risk factors on the accumulation of amyloid plaques and neurofibrillary tangles, alter brain structure and blood flow, and influence cognition in middle age. The first study was conducted to assess the effects of insulin resistance on cognitive decline over a 4-10 year period, and demonstrated that indeed, insulin resistance is associated with cognitive trajectories. The next three studies were aimed at identifying changes in AD biomarkers in CSF and brain imaging as predicted by insulin resistance, body mass index and abdominal obesity. The main findings indicate that elevated insulin resistance at midlife may affect amyloid processing as indicated by altered CSF levels, as well as acting via a tau-related mechanism, an effect that differed by APOE [epsilon]4 genotype. Given that tau in CSF is likely originating from axons, this finding was followed up by a neuroimaging study employing diffusion tensor imaging to examine the effects of insulin resistance and APOE [epsilon]4 on neural microstructure. Similar to the findings in CSF, the effects of insulin resistance on microstructure differed by APOE [epsilon]4 genotype. Finally, my studies of abdominal obesity suggest that this risk factor is not associated with amyloid or tau pathology as measured in CSF, nor microstructural changes, yet central obesity was associated with moderate effects on cerebral blood flow. In conclusion, the work presented in my thesis demonstrates a robust effect of insulin resistance on cognitive and biomarker outcomes in midlife, which may explain the increased risk of developing AD.
Author: Erika Jane Starks
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Dementia due to Alzheimer's disease (AD) is a devastating condition characterized clinically by progressive cognitive impairment and pathologically by amyloid plaques, neurofibrillary tangles and severe atrophy. Diabetes mellitus (DM), obesity, and associated insulin resistance in middle age, are linked to a greater risk of developing dementia due to AD. Given the potential of modifying metabolic risk factors at midlife, my research explored the pathophysiological mechanisms involved in the link between insulin resistance and obesity at middle-age and AD pathology using molecular and imaging biomarkers. Specifically, my studies aimed to investigate the potential effect of metabolic risk factors on the accumulation of amyloid plaques and neurofibrillary tangles, alter brain structure and blood flow, and influence cognition in middle age. The first study was conducted to assess the effects of insulin resistance on cognitive decline over a 4-10 year period, and demonstrated that indeed, insulin resistance is associated with cognitive trajectories. The next three studies were aimed at identifying changes in AD biomarkers in CSF and brain imaging as predicted by insulin resistance, body mass index and abdominal obesity. The main findings indicate that elevated insulin resistance at midlife may affect amyloid processing as indicated by altered CSF levels, as well as acting via a tau-related mechanism, an effect that differed by APOE [epsilon]4 genotype. Given that tau in CSF is likely originating from axons, this finding was followed up by a neuroimaging study employing diffusion tensor imaging to examine the effects of insulin resistance and APOE [epsilon]4 on neural microstructure. Similar to the findings in CSF, the effects of insulin resistance on microstructure differed by APOE [epsilon]4 genotype. Finally, my studies of abdominal obesity suggest that this risk factor is not associated with amyloid or tau pathology as measured in CSF, nor microstructural changes, yet central obesity was associated with moderate effects on cerebral blood flow. In conclusion, the work presented in my thesis demonstrates a robust effect of insulin resistance on cognitive and biomarker outcomes in midlife, which may explain the increased risk of developing AD.
Author: Akhlaq A. Farooqui
Publisher: Springer Science & Business Media
ISBN: 1461473187
Category : Medical
Languages : en
Pages : 429
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Book Description
Metabolic syndrome as an important risk factor for stroke, Alzheimer disease, and depression presents readers with cutting edge and comprehensive information on relationship among metabolic syndrome, stroke, Alzheimer disease, and depression. It is hoped that this monograph will be useful to postgraduate students, faculty, research scientists, pharmacologists, nutritionists, and physicians, who are curious about the molecular mechanisms that link metabolic syndrome with stroke, Alzheimer disease, and depression.
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: Beller Health
Publisher: Independently Published
ISBN: 9781097268511
Category :
Languages : en
Pages : 114
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Book Description
Book 9 focuses on a new dementia type, LATE, mistaken as Alzheimer's disease until now.LATE stands for Limbic-predominant age-related TDP-43 encephalopathy, the protein buildup responsible for this dementia. This book is organic, like the series, meaning we never consider our books as finished. Science evolves, which is why our books go through continuous updates. Since LATE is a new dementia classification, we expect continuous further information to emerge. Watch Amazon alerts for potential digital updates. We provide free digital copies on all paperback purchases, so everybody receives free updates.
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: Ruocheng Dong (Ph.D.)
Publisher:
ISBN:
Category :
Languages : en
Pages : 128
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Book Description
The recent advancements of untargeted metabolomics and the strategy of metabolome-wide association study (MWAS) enable us to incorporate metabolomics data in different tissue, e.g., blood and cerebrospinal fluid (CSF), and open a window to study the biological mechanisms of Alzheimer's disease (AD), especially in the preclinical stage. Using longitudinal and multi-omics data from the Wisconsin Registry for Alzheimer's Prevention (WRAP) and Wisconsin Alzheimer's Disease Research Center (ADRC) cohorts, we investigated the relationships between plasma and CSF metabolites, modifiable risk factors, genomics, and AD endophenotypes. First of all, by integrating plasma metabolites, modifiable risk factors of AD, including the MIND diet, physical activity, smoking and caffeine intake, and AD endophenotypes, e.g., CSF biomarkers and cognitive functions, we improved our knowledge about the potential metabolic changes associated with modifiable risk factors and their relationship with AD pathology. Second, we identified several CSF metabolites, e.g., phospholipids and metabolic pathways associated with different AD pathologies, and confirmed the causal effect of some metabolites based on Mendelian randomization. Finally, calculating and evaluating the polygenic risk score (PRS) for AD and AD endophenotypes based on traditional and recently developed methods offers valuable insight into AD PRS research. The combination of PRS and MWAS presents an example of integrating multi-omics data and extending the application of PRS. In general, the findings from this dissertation provide a solid foundation for future investigations of omics, pathology, environment impact, and the discovery of biomarkers in AD research, therefore, to help the prevention, diagnosis, and ultimately the therapy of AD.
Author: National Academies of Sciences Engineering and Medicine
Publisher:
ISBN: 9780309495035
Category :
Languages : en
Pages :
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Book Description
As the largest generation in U.S. history - the population born in the two decades immediately following World War II - enters the age of risk for cognitive impairment, growing numbers of people will experience dementia (including Alzheimer's disease and related dementias). By one estimate, nearly 14 million people in the United States will be living with dementia by 2060. Like other hardships, the experience of living with dementia can bring unexpected moments of intimacy, growth, and compassion, but these diseases also affect people's capacity to work and carry out other activities and alter their relationships with loved ones, friends, and coworkers. Those who live with and care for individuals experiencing these diseases face challenges that include physical and emotional stress, difficult changes and losses in their relationships with life partners, loss of income, and interrupted connections to other activities and friends. From a societal perspective, these diseases place substantial demands on communities and on the institutions and government entities that support people living with dementia and their families, including the health care system, the providers of direct care, and others. Nevertheless, research in the social and behavioral sciences points to possibilities for preventing or slowing the development of dementia and for substantially reducing its social and economic impacts. At the request of the National Institute on Aging of the U.S. Department of Health and Human Services, Reducing the Impact of Dementia in America assesses the contributions of research in the social and behavioral sciences and identifies a research agenda for the coming decade. This report offers a blueprint for the next decade of behavioral and social science research to reduce the negative impact of dementia for America's diverse population. Reducing the Impact of Dementia in America calls for research that addresses the causes and solutions for disparities in both developing dementia and receiving adequate treatment and support. It calls for research that sets goals meaningful not just for scientists but for people living with dementia and those who support them as well. By 2030, an estimated 8.5 million Americans will have Alzheimer's disease and many more will have other forms of dementia. Through identifying priorities social and behavioral science research and recommending ways in which they can be pursued in a coordinated fashion, Reducing the Impact of Dementia in America will help produce research that improves the lives of all those affected by dementia.
Author: Ruocheng Dong (Ph.D.)
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
The recent advancements of untargeted metabolomics and the strategy of metabolome-wide association study (MWAS) enable us to incorporate metabolomics data in different tissue, e.g., blood and cerebrospinal fluid (CSF), and open a window to study the biological mechanisms of Alzheimer's disease (AD), especially in the preclinical stage. Using longitudinal and multi-omics data from the Wisconsin Registry for Alzheimer's Prevention (WRAP) and Wisconsin Alzheimer's Disease Research Center (ADRC) cohorts, we investigated the relationships between plasma and CSF metabolites, modifiable risk factors, genomics, and AD endophenotypes. First of all, by integrating plasma metabolites, modifiable risk factors of AD, including the MIND diet, physical activity, smoking and caffeine intake, and AD endophenotypes, e.g., CSF biomarkers and cognitive functions, we improved our knowledge about the potential metabolic changes associated with modifiable risk factors and their relationship with AD pathology. Second, we identified several CSF metabolites, e.g., phospholipids and metabolic pathways associated with different AD pathologies, and confirmed the causal effect of some metabolites based on Mendelian randomization. Finally, calculating and evaluating the polygenic risk score (PRS) for AD and AD endophenotypes based on traditional and recently developed methods offers valuable insight into AD PRS research. The combination of PRS and MWAS presents an example of integrating multi-omics data and extending the application of PRS. In general, the findings from this dissertation provide a solid foundation for future investigations of omics, pathology, environment impact, and the discovery of biomarkers in AD research, therefore, to help the prevention, diagnosis, and ultimately the therapy of AD.
