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

基本信息

批准号：
10534237
负责人：
Yuri Agrawal
金额：
$ 72.35万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-02-01 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10534237
关键词：
3-Dimensional Accelerometer Adult Age Aging Alzheimer disease prevention Alzheimer&apos s Disease Alzheimer&apos s disease diagnosis Alzheimer&apos s disease pathology Alzheimer&apos 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 Disease Progression Early identification 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 Phase Phenotype Physical Function Physical activity Physical therapy Physiological Pittsburgh Compound-B Positron-Emission Tomography Predictive Value Procedures Prospective Studies Protocols documentation Psychometrics Rehabilitation therapy Research Resources Risk Role Sensorimotor functions Sensory Societies Speed Symptoms System Technology Time Training Validation Visit Visual Visual impairment Work abeta deposition aged aging brain cerebral atrophy cognitive function cognitive performance cognitive testing data resource disorder risk experience gait correction gait examination hearing impairment high risk improved insight lens mild cognitive impairment novel performance tests pharmacologic pre-clinical pre-clinical assessment predictive modeling prevent progression risk risk prediction model tau Proteins tau aggregation tau-1

项目摘要

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.

项目摘要阿尔茨海默氏病（AD）是痴呆症的最常见原因。基础病理和生理据信与AD的发作和进展有关的变化在临床前几年出现表现。感觉障碍，步态异常和运动放慢可能是AD诊断之前的到十年或更长时间以上，感觉运动功能变化的令人兴奋的可能性可能会充当 AD的早期无创生物标志物。我们小组的先前工作已经确定了认知之间的联系性能和感觉障碍并满足速度和可变性，使它们具有潜在的临床前标记早期广告病理学。我们建议最多使用10年的现有纵向数据，并持续/新数据在巴尔的摩纵向研究（BLSA）的大约1,000名老年人中收集感觉功能的作用，速度和变异性以及每日体育锻炼的自由生活量度（PA）作为认知障碍的前体。我们还将确定感觉运动测量和 AD病理学的生物标志物，包括使用[11C] -Pittsburgh化合物B Polaron发射的Aβ沉积层析成像，使用结构磁共振成像（MRI），tau和PTAU的脑萎缩流体和认知表现。我们将进一步利用BLSA的丰富数据资源来开发 Parsimonius的预测模型是向MCI/AD发展的风险，并验证其在社区（ARIC）研究中的动脉粥样硬化风险。更好地理解感觉运动变化，亚临床AD病理和认知性能可能阐明高风险表型随着时间的流逝，认知结果不良的风险增加，并增加了我们对随着年龄的增长，感官，身体和认知功能下降之间的复杂关联。为此，预防AD的未来干预研究可能会筛选感官障碍作为高风险表型反映了开发AD的风险增加，这可以作为临床试验中的替代结果。此外，感觉运动障碍可能会构成可行且可修改的目标，以预防AD 确定实施辅助和康复技术（例如听力）的关键阈值艾滋病，纠正镜，外科或药物的结肠化程序，以纠正听力和/或视力障碍（例如，白内障手术，人工耳蜗）以及运动训练的物理疗法/时间安排正确的步态异常。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cross-sectional associations between multisensory impairment and brain volumes in older adults: Baltimore Longitudinal Study of Aging.

老年人多感觉障碍与脑容量之间的横断面关联：巴尔的摩老龄化纵向研究。

DOI：
10.1038/s41598-024-59965-w
发表时间：
2024
期刊：
Scientific reports
影响因子：
4.6
作者：
Tian,Chenxin;Schrack,JenniferA;Agrawal,Yuri;An,Yang;Cai,Yurun;Wang,Hang;Gross,AldenL;Tian,Qu;Simonsick,EleanorM;Ferrucci,Luigi;Resnick,SusanM;Wanigatunga,AmalA
通讯作者：
Wanigatunga,AmalA