Preclinical Alzheimer Disease and Driving

项目摘要/摘要 这项研究的目标是描述阿尔茨海默病(AD)大脑的长期影响 临床前阿尔茨海默病患者和非阿尔茨海默病患者的驾驶行为和停止驾驶的病理学。我们的 结果表明，阿尔茨海默病的长期临床前阶段，反映在淀粉样蛋白成像和脑脊液 认知正常者的脑脊液生物标志物与较差的驾驶性能有关。 标准化路考。 这项研究意义重大，因为3600万持有执照的司机年龄在65岁或以上，而 预计到2050年，美国老年人的数量将翻一番，届时每4名司机中就有一人年龄为65岁 或者更老。机动车碰撞是老年人受伤和死亡的主要原因。辨别的能力 谁是驾驶衰退的最大风险，以及何时发生驾驶衰退的预测将有助于早期驾驶安全 针对老年人的干预试验。临床前AD是规划和实施AD的重要阶段 预计驾驶技能会随着疾病进展而发生变化的安全措施。 我们的具体目标将决定新的和成熟的AD生物标志物和 其他与年龄和疾病相关的因素与整个临床前过程中的驾驶表现有关 AD：(1)保持和发展我们独特的患有和不患有临床前AD的老年司机队列。(2)至 检验临床前AD是否能预测自然驱动力的横断面差异和纵向变化。 (3)识别驾驶、生物标志物、临床、身体和行为预测因素，并 使用这些变量开发预测模型。 为了测试这些具体目标，我们组建了一个拥有AD专业知识的多学科团队， 神经成像生物标记物，脑脊液生物标记物，一般驾驶，特别是自然主义驾驶，认知和 脑老化和纵向生物统计学方法。我们将利用现有的基础设施来遵循我们的 目前队列中有180名认知正常的AD患者和没有临床前AD患者，并增加了其他 参与者创建一个300人的队列。这一更大的群体将继续进行年度驾驶 测试，以及利用自然主义驾驶方法，将捕捉他们的驾驶行为在每天 基础。AD脑病理的长期影响将通过几种方式来定义，以帮助了解其影响 关于驾驶表现、行为和戒烟。此外，我们还将创建驾驶预测模型 停止。 一旦获得这些知识，就可以用来创建适合阶段的、个性化的、与驾驶相关的 安全策略，可在诊断后实施，并在疾病进展过程中进行调整。

PROJECT SUMMARY/ABSTRACT The goal of this research is to characterize the long-term impact of Alzheimer disease (AD) brain pathology on driving behavior and driving cessation among persons with and without preclinical AD. Our findings indicate that the long preclinical stage of AD, as reflected in amyloid imaging and cerebrospinal fluid (CSF) biomarkers among cognitively normal persons, is associated with poorer driving performance on a standardized road test. This research is significant because 36 million licensed drivers are aged 65 years or older, and the number of older adults in the United States is expected to double by 2050, when 1 in 4 drivers will be 65 years or older. Motor vehicle crashes are a leading cause of injury and death in older adults. The ability to identify who will be at most risk of driving decline and to predict when decline will occur will inform early driving safety intervention trials for older adults. Preclinical AD is an important stage during which to plan and implement safety measures in anticipation of changes in driving skills with disease progression. Our Specific Aims will determine how levels of both novel and well-established AD biomarkers and other age- and disease-associated factors are related to driving performance across the course of preclinical AD: (1) To maintain and grow our unique cohort of older adult drivers with and without preclinical AD. (2) To test whether preclinical AD predicts cross-sectional differences and longitudinal changes in naturalistic driving. (3) To identify driving, biomarker, clinical, physical, and behavioral predictors of driving cessation, and to develop predictive models using these variables. To test these Specific Aims, we have assembled a multidisciplinary team with expertise in AD, neuroimaging biomarkers, CSF biomarkers, driving generally, naturalistic driving specifically, cognitive and brain aging, and longitudinal biostatistical methods. We will capitalize on existing infrastructure to follow our current cohort of 180 cognitively normal participants with and without preclinical AD, and add additional participants to create a cohort of 300 individuals. This larger cohort will continue to undergo an annual driving test, as well as utilize a naturalistic driving methodology that will capture their driving behaviors on an everyday basis. The long-term impact of AD brain pathology will be defined in several ways to help understand its impact on driving performance, behavior, and cessation. Additionally, we will create predictive models of driving cessation. Once obtained, this knowledge can be used to create stage-appropriate, personalized, driving-related safety strategies that can be implemented upon diagnosis, and adjusted throughout disease progression.