Multisensory, Motor, and Biomarker Changes in Aging and Preclinical Alzheimer's Disease

衰老和临床前阿尔茨海默病的多感觉、运动和生物标志物变化

• 批准号: 10814554
• 负责人: Natascha Merten
• 金额: $ 15.37万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10814554
• 关键词: Adult; Adult Children; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-42; Amyloid beta-Protein; Ancillary Study; Baby Booms; Behavioral; Biological Assay; Biological Markers; Biological Models; Brain; Caring; Clinical; Cognition; Cognitive; Cognitive aging; Cohort Studies; Data; Dementia; Development; Diabetes Mellitus; Elderly; Epidemiology; Future; Generations; Genetic Risk; Hearing; High birth weight infant; Impaired cognition; Impairment; Inflammation; Inner Plexiform Layer; Intervention; Least-Squares Analysis; Light; Linear Regressions; Longitudinal Studies; Longitudinal cohort study; Measures; Metabolic Diseases; Methods; Modeling; Modification; Motor; National Institute on Alcohol Abuse and Alcoholism; Nerve Degeneration; Neuronal Injury; Neurotoxins; Olfactory dysfunction; Optical Coherence Tomography; Outcome; Participant; Pathologic; Pathology; Persons; Phenotype; Predictive Value; Public Health; Research; Resources; Risk; Risk Factors; Role; Sampling; Sensory; Serum; Smell Perception; Symptoms; System; Taste Perception; Testing; Thick; Time; Trail Making Test; United States National Institutes of Health; Vascular Diseases; Vision; Visual impairment; Vitamins; age related; clinical diagnosis; clinically significant; cognitive change; cognitive function; cohort; follow-up; functional outcomes; ganglion cell; hearing impairment; high risk; improved; macula; middle age; motor disorder; motor impairment; multisensory; neurofilament; neuropathology; offspring; parent grant; population based; pre-clinical; predictive modeling; preservation; response; risk prediction; risk prediction model; social; tau Proteins

PARENT GRANT ABSTRACT (RF1 AG066837) Alzheimer’s disease (AD) and other causes of cognitive impairment are growing public health problems with the aging of the large baby boom generation and there is a shortage of workers and facilities to meet the future care needs of those with AD and other dementias. AD-related brain changes may occur years or decades before the onset of symptoms and, therefore, it is important to identify, in midlife, people at high risk for AD to provide ample opportunity to intervene when it may be possible to delay the onset of clinically significant symptoms and loss of independence. Longitudinal studies have shown that sensory (hearing, vision, olfaction) and motor impairments are associated with increased risk of cognitive impairment, dementia, or AD. This project is to study the impact of aging changes in sensory function (hearing, olfaction, vision, and taste) and motor function on the 10-yr risk of pre-clinical AD in middle-aged adults. The Beaver Dam Offspring Study is a longitudinal cohort study of sensory and cognitive aging in the adult offspring of the population-based Epidemiology of Hearing Loss Study cohort. Data from participants (N=1536, mean age 49 years) who have stored serum samples from the baseline (2005-2008), 5-yr follow-up (2010-2013) and 10-yr follow-up (2015- 2017) examinations will be included. Stored samples from the three time points will be assayed for serum amyloid β40 and β42 (Aβ40, Aβ42), serum total tau (TT) and neurofilament light chain (NfL); biomarkers of Alzheimer’s pathology, neuronal injury and neurodegeneration. Least squares multiple linear regression models and longitudinal linear mixed effects models will be used to determine if sensory and motor function and other traditional risk factors for AD and dementia are associated with levels of Aβ, TT and NfL at baseline and 10-year change, respectively, in these serum biomarkers. The biomarkers, Aβ, TT and NfL, and thickness of the macular ganglion cell inner plexiform layer (mGCIPL) will be applied to a modification of the NIA-Alzheimer’s Association AT(N) framework to identify preclinical Alzheimer’s and non-Alzheimer’s neuropathology in midlife. Using this modified framework and traditional cognitive outcomes we will determine if sensory and motor changes in aging contribute to 10-year risk prediction models for biologically and functionally defined preclinical AD. The best prediction model results will be extended to create clinically useful risk scores. Risk scores for asymptomatic middle-aged people which are based on practical test batteries will be useful in clinical and research settings.

家长补助金摘要 (RF1 AG066837) 阿尔茨海默病 (AD) 和其他导致认知障碍的原因正在日益严重的公共卫生问题 婴儿潮一代老龄化，劳动力和设施短缺，无法满足未来需求 AD 和其他痴呆症患者的护理需求可能会发生数年或数十年。 在症状出现之前，因此，在中年时识别 AD 高危人群非常重要 当有可能延迟具有临床意义的疾病的发生时，提供充足的干预机会 纵向研究表明，感觉（听觉、视觉、嗅觉）会导致症状和丧失独立性。 运动障碍与认知障碍、痴呆或 AD 的风险增加有关。 该项目旨在研究衰老变化对感觉功能（听觉、嗅觉、视觉和味觉）的影响 Beaver Dam 后代研究是一项运动功能对中年成人临床前 AD 风险的影响。 基于人群的成年后代感觉和认知衰老的纵向队列研究 听力损失流行病学研究队列的数据来自患有听力损失的参与者（N=1536，平均年龄 49 岁）。 储存基线（2005-2008）、5年随访（2010-2013）和10年随访（2015-2015）的血清样本 2017）将包括三个时间点存储的样本的血清检测。 淀粉样蛋白 β40 和 β42 (Aβ40、Aβ42)、血清总 tau (TT) 和神经丝轻链 (NfL) 生物标志物； 阿尔茨海默病病理学、神经元损伤和神经变性。 最小二乘多元线性回归模型和纵向线性混合效应模型将用于 确定感觉和运动功能以及 AD 和痴呆症的其他传统风险因素是否相关 这些血清生物标志物中的 Aβ、TT 和 NfL 水平分别在基线和 10 年变化。 生物标志物 Aβ、TT 和 NfL，以及黄斑神经节细胞内丛状层 (mGCIPL) 的厚度将 应用于 NIA-阿尔茨海默病协会 AT(N) 框架的修改，以识别临床前阿尔茨海默病 以及中年非阿尔茨海默病的神经病理学。 我们将确定衰老过程中的感觉和运动变化是否有助于 10 年风险预测模型 对于生物学和功能定义的临床前 AD 的最佳预测模型结果将扩展到 为无症状中年人创建临床上有用的风险评分。 实际测试电池将在临床和研究环境中有用。