FALLS: A MARKER OF PRECLINICAL ALZHEIMERS DISEASE

项目摘要/摘要 这项建议将研究临床前阿尔茨海默病(AD)老年人的跌倒。转换为 症状性AD不是一个直接的过程；相反，它在一系列临床前阶段缓慢发展。 尽管症状性AD的特征是进行性认知问题，但越来越多的证据表明 功能活动异常和跌倒增加可能先于认知障碍。瀑布是一个领先的 导致老年人口发病和死亡的原因。老年AD患者的风险是前者的两倍以上 与普通人群相比，下降的可能性更大。对日常功能的衡量目前不包括在 认知正常的临床前阿尔茨海默病患者的评估。在一群特征明确的老年人中， 接受奈特阿尔茨海默病研究的认知正常的人(65岁) 中心，我们将进行纵向的家庭评估，以定量评估跌倒和功能 机动性。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， 神经退化的证据)导致大脑网络的功能连接发生变化。这些大脑 网络变化既影响中枢神经系统标志物(如认知能力)，也影响外周 神经系统标记物(如平衡、力量、视力和感觉)。我们建议一种协同效应 中枢和外周改变之间的相互作用导致功能移动性改变，导致增加 在秋天。我们的发现将通过在临床前识别新的“真实世界”生物标志物来推动AD领域的发展 AD的各个阶段。在家庭环境中对跌倒和步态不稳定性的评估可能会成为一种潜在的 廉价、非侵入性的筛查工具，可识别转换为 症状性AD。这可能对二级预防干预的时机有重要影响。 公元后的试验。

PROJECT 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.