Naturalistic driving as a functional neurobehavioral marker of preclinical and symptomatic Alzheimer disease

项目总结/摘要 我们的长期目标是准确识别谁有驾驶能力下降的风险， 行为可以作为阿尔茨海默病（AD）的功能性神经行为生物标志物， 驾驶下降将发生，干预下降之前的时间，并防止大量的 车祸受伤和死亡我们的研究结果表明，阿尔茨海默病的长期临床前阶段，如淀粉样蛋白， 和tau成像和脑脊液（CSF）生物标志物之间的认知正常的老年人， 道路测试中的驾驶性能较差，以及在个人车辆中进行的行程较少。这 该项目将测试车载数据记录器，连续测量日常驾驶行为， 反映了潜在的神经病理性AD，并与普遍和偶发的认知障碍有关。 这项研究意义重大，因为3600万持牌司机年龄在65岁或以上， 到2050年，美国老年人的数量预计将翻一番，届时四分之一的司机将超过65岁。我们 这项研究表明，驾驶的变化，一种涉及认知和 功能能力，可能反映神经病理性AD和痴呆症状的出现之前。 我们的具体目标是（1）使用已建立的脑脊液（CSF）和成像生物标志物来定义 临床前AD和测试驾驶真实世界车载评估系统（DRIVES）的能力， 在认知正常个体中区分患有和不患有临床前AD的人，并评估 （2）测试DRIVES数据区分痴呆的能力 认知正常的人与痴呆症患者的横断面，并检查驾驶行为， （3）确定DRIVES数据是否与认知、健康、功能 来自老年人的数据可以改善对认知障碍和痴呆的预测。 为了测试这些特定目标，我们组建了一个具有AD专业知识的多学科团队， 神经成像生物标志物（淀粉样蛋白和tau），流体生物标志物（CSF和血液），自然驾驶，空间 导航，认知和大脑老化，以及纵向生物统计方法。我们将利用现有的 机构基础设施纵向跟踪300名认知正常的老年人和50名老年人， 轻度或非常轻度的痴呆症，以创建一个350人的队列。这一组将使用自然主义的 驾驶方法，将捕捉他们的日常驾驶行为。他们的认知将受到考验 每年使用临床痴呆症评级和各种神经心理学措施。 一旦获得，这些知识可以用来绘制驾驶作为神经行为生物标志物， 监测并用于临床试验和AD整个疾病进展的干预。

PROJECT SUMMARY/ABSTRACT Our long-term goal is to accurately identify who is at risk of driving decline, to establish whether driving behavior can be used as a functional, neurobehavioral biomarker of Alzheimer disease (AD), to forecast when driving decline will occur, to intervene before the time of decline, and to prevent a significant number of crashes, injuries, and death. Our findings indicate that the long preclinical stage of AD, as reflected in amyloid and tau imaging and cerebrospinal fluid (CSF) biomarkers among cognitively normal older adults, is associated with poorer driving performance on a road test, as well as with fewer trips made in a personal vehicle. This project will test the extent to which an in-vehicle datalogger, measuring everyday driving behavior continuously, reflects underlying neuropathological AD and is associated with prevalent and incident cognitive impairment. 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+. Our work suggests that changes in driving, an instrumental activity of daily living that involves both cognitive and functional abilities, may reflect neuropathological AD and precede the emergence of dementia symptoms. Our Specific Aims will (1) Use established cerebrospinal fluid (CSF) and imaging biomarkers to define preclinical AD and test the ability of the Driving Real-world In-Vehicle Evaluation System (DRIVES) to distinguish persons with and without preclinical AD among cognitively normal individuals, and assess the ability of this system to predict the future onset of dementia, (2) Test the ability of the DRIVES data to distinguish cognitively normal persons from those with dementia cross-sectionally, and to examine driving behavior over time for both groups, (3) Determine whether the DRIVES data, combined with cognitive, health, and functional data from older adults, can improve prediction of incident cognitive impairment and dementia. To test these Specific Aims, we have assembled a multidisciplinary team with expertise in AD, neuroimaging biomarkers (amyloid and tau), fluid biomarkers (CSF and blood), naturalistic driving, spatial navigation, cognitive and brain aging, and longitudinal biostatistical methods. We will capitalize on existing institutional infrastructure to longitudinally follow 300 cognitively normal older adults and 50 older adults with mild or very mild dementia, to create a cohort of 350 individuals. This cohort will be followed using a naturalistic driving methodology that will capture their driving behaviors on a daily basis. Their cognition will be tested annually using the Clinical Dementia Rating and various neuropsychological measures. Once obtained, this knowledge can be used to map driving as a neurobehavioral biomarker that may be monitored and used for clinical trials and interventions throughout disease progression of AD.