Contribution of sensorimotor function to risk and pathogenic mechanisms of Alzheimer's disease and related dementias

感觉运动功能对阿尔茨海默病和相关痴呆的风险和致病机制的贡献

• 批准号: 10318172
• 负责人: Yuri Agrawal
• 金额: $ 72.9万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10318172
• 关键词: 3-Dimensional; Accelerometer; Address; Adult; Age; Aging; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Amyloid beta-Protein; Atherosclerosis Risk in Communities; Atrophic; Auditory; Baltimore; Biological Markers; Blindness; Brain; Cataract Extraction; Cerebrospinal Fluid; Clinical; Clinical Trials; Cochlear Implants; Cognitive; Communities; Complex; Consensus; Data; Data Collection; Dementia; Deterioration; Diagnosis; Disease Progression; Elderly; Family; Future; Gait; Gait abnormality; Gait speed; Goals; Health; Hearing Aids; Impaired cognition; Impairment; Individual; Intervention; Intervention Studies; Joints; Knowledge; Laboratories; Life Style; Link; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Modeling; Monitor; Motion; Motor; Movement; Operative Surgical Procedures; Outcome; Participant; Pathogenicity; Pathologic; Pathology; Performance; Pharmacology; Phase; Phenotype; Physical Function; Physical activity; Physical therapy; Physiological; Pittsburgh Compound-B; Positron-Emission Tomography; Predictive Value; Procedures; Prospective Studies; Protocols documentation; Psychometrics; Research; Resources; Risk; Role; Self-Help Devices; Sensorimotor functions; Sensory; Societies; Symptoms; Time; Training; Validation; Visit; Visual; Visual impairment; Work; abeta accumulation; abeta deposition; aged; aging brain; base; cerebral atrophy; cognitive function; cognitive performance; cognitive testing; data resource; disorder risk; experience; gait examination; hearing impairment; high risk; improved; insight; lens; mild cognitive impairment; novel; performance tests; pre-clinical; pre-clinical assessment; predictive modeling; prevent; rehabilitation technology; risk prediction model; sensorimotor system; tau Proteins; tau aggregation; tau-1

PROJECT SUMMARY Alzheimer's disease (AD) is the most common cause of dementia. Underlying pathological and physiological changes related to the onset and progression of AD are believed to emerge several years prior to clinical manifestations. Sensory impairments, gait abnormalities, and motor slowing may precede the diagnosis of AD by a decade or more, presenting the exciting possibility that changes in sensorimotor functioning may act as early noninvasive biomarkers for AD. Previous work by our group has identified links between cognitive performance and sensory impairment and gait speed and variability, making them potential preclinical markers of early AD pathology. We propose to use up to 10 years of existing longitudinal data, and ongoing/new data collection in approximately 1,000 older adults in the Baltimore Longitudinal Study of Aging (BLSA), to examine the roles of sensory function, gait speed and variability, and free-living measures of daily physical activity (PA) as precursors to cognitive impairment. We will also determine the link between sensorimotor measures and biomarkers of AD pathology, including Aβ deposition using [11C]-Pittsburgh compound B positron emission tomography, brain atrophy using structural magnetic resonance imaging (MRI), Tau and pTau from cerebrospinal fluid, and cognitive performance. We will further utilize the rich data resources of the BLSA to develop a parsimonius prediction model for risk of progression to MCI/AD, and validate its performance in the Atherosclerosis Risk in Communities (ARIC) study. A better understanding of the associations among sensorimotor changes, subclinical AD pathology, and cognitive performance may elucidate a high-risk phenotype that is associated with increased risk of poor cognitive outcomes over time and increase our understanding of the complex associations among declines in sensory, physical, and cognitive functioning with age. To this end, future intervention studies of AD prevention might screen for sensorimotor impairments as a high-risk phenotype reflective of increased risk for developing AD, which could serve as surrogate outcomes in clinical trials. Moreover, sensorimotor impairments may present feasible and modifiable targets for AD prevention by identifying critical threshold(s) for implementation of assistive and rehabilitative technologies such as hearing aids, corrective lenses, surgical or pharmacologic procedures to correct hearing and/or vision impairment (e.g., cataract surgery, cochlear implants), and physical therapy/timing and coordination of movement training to correct gait abnormalities.

项目概要 阿尔茨海默病（AD）是痴呆症最常见的原因。潜在的病理和生理 据信，与 AD 发病和进展相关的变化在临床前几年就出现了。 表现形式。感觉障碍、步态异常和运动减慢可能先于 AD 诊断 十年或更长时间，感觉运动功能的变化可能会起到令人兴奋的作用 AD 的早期非侵入性生物标志物。我们小组之前的工作已经确定了认知之间的联系 表现和感觉障碍以及步态速度和变异性，使它们成为潜在的临床前标志物 早期 AD 病理学。我们建议使用长达 10 年的现有纵向数据以及持续/新数据 巴尔的摩老龄化纵向研究 (BLSA) 收集了大约 1,000 名老年人，以检查 感觉功能、步态速度和变异性以及日常身体活动 (PA) 的自由生活测量的作用 作为认知障碍的先兆。我们还将确定感觉运动测量与 AD 病理学的生物标志物，包括使用 [11C]-匹兹堡化合物 B 正电子发射的 Aβ 沉积 断层扫描、使用结构磁共振成像 (MRI) 的脑萎缩、脑脊液中的 Tau 和 pTau 流体和认知表现。我们将进一步利用BLSA丰富的数据资源，开发 简约预测模型进展为 MCI/AD 的风险，并验证其在 社区动脉粥样硬化风险 (ARIC) 研究。更好地理解它们之间的关联 感觉运动变化、亚临床 AD 病理学和认知表现可能阐明高风险表型 随着时间的推移，这与认知结果不佳的风险增加相关，并增加我们对 随着年龄的增长，感觉、身体和认知功能下降之间存在着复杂的关联。为此， 未来 AD 预防的干预研究可能会将感觉运动障碍作为一种高风险表型进行筛查 反映了患 AD 的风险增加，这可以作为临床试验的替代结果。 此外，感觉运动障碍可能为 AD 预防提供可行且可修改的目标 确定实施辅助和康复技术（例如听力）的关键阈值 矫正听力和/或视力障碍的辅助器具、矫正镜片、手术或药物程序（例如， 白内障手术、人工耳蜗）以及物理治疗/运动训练的时机和协调 纠正步态异常。