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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：
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
项目类别：
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&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 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

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.

项目总结