FALLS: A MARKER OF PRECLINICAL ALZHEIMERS DISEASE

总结/摘要 这项提案将研究福尔斯在老年人与临床前阿尔茨海默氏病（AD）。改划为 症状性AD不是一个立即的过程;相反，它在一系列临床前阶段缓慢发展。 虽然症状性AD的特征是进行性认知问题，但越来越多的证据表明， 功能性活动异常和福尔斯增加可能先于认知损害。福尔斯是 老年人发病率和死亡率的原因。老年AD患者的风险超过两倍 与一般人群相比，福尔斯的死亡率。日常功能的测量目前不包括在 临床前AD认知正常个体的评估。在一组特征明确的老年人中， 认知正常的人（>65岁），由Knight Alzheimer's Disease Research 中心，我们将在家中进行纵向评估，以定量评估福尔斯和功能 迁移率我们假设脑神经病理学（例如，淀粉样蛋白和/或tau蛋白的存在， 神经变性的证据）导致大脑网络的功能连接的变化。这些脑 网络变化影响中枢神经系统标记（例如，认知性能）和外围 神经系统标记物（例如，平衡、力量、视觉和感觉）。我们建议， 中枢和外周变化之间的相互作用导致功能活动性改变，从而增加 在福尔斯。我们的发现将通过在临床前研究中识别新的“真实世界”生物标志物来推进AD领域。 AD的阶段。在家庭环境中评估福尔斯和步态不稳可能作为一种潜在的 廉价和非侵入性的筛选工具，以确定个人在最大的风险转换为 症状性AD这可能对二级预防干预的时机有重要影响 在AD的审判

SUMMARY/ABSTRACT This proposal will study falls in older adults with preclinical Alzheimer’s disease (AD). Conversion to symptomatic AD is not an immediate process; rather, it develops slowly over a series of preclinical stages. Although symptomatic AD is characterized by progressive cognitive problems, growing evidence suggests that functional mobility abnormalities and an increase in falls may precede cognitive impairment. Falls are a leading cause of morbidity and mortality in the older adult population. Older AD patients have more than twice the risk of falls compared to the general population. Measures of everyday function are currently not included in the evaluation of cognitively normal individuals with preclinical AD. Within a well-characterized cohort of older, cognitively normal individuals (>65 years old) who are followed by the Knight Alzheimer’s Disease Research Center, we will perform longitudinal in-home assessments to quantitatively evaluate falls and functional mobility. We hypothesize that brain neuropathology (e.g., the presence of amyloid and/or tau proteins, evidence of neurodegeneration) lead to changes in functional connectivity of brain networks. These brain network changes affect both central nervous system markers (e.g., cognitive performance) and peripheral nervous system markers (e.g., balance, strength, vision, and sensation). We suggest that a synergistic interaction between central and peripheral changes leads to altered functional mobility, resulting in an increase in falls. Our findings will advance the field of AD by identifying novel “real-world” biomarkers in preclinical stages of AD. Assessment of falls and gait instability in the home setting could potentially serve as an inexpensive and non-invasive screening tool to identify individuals at greatest risk for conversion to symptomatic AD. This may have important implications for the timing of interventions in secondary prevention trials in AD.