This research project tackles the NIH/NIA grand challenge of using a person's own vehicle as a passive-detection system for flagging potential age- and disease-related aberrant driving that may signal early warning signs of functional decline or incipient Alzheimer's disease (AD). Early identification and treatment are essential steps to mitigating the growing costs and burden of AD. Our foundational advancements in quantifying driver behavior from in-vehicle systems ("Black Boxes") and wearable sensors, and strategic analytic methods and pipelines using statistical and machine learning approaches, are directly relevant to meeting this NIH/NIA challenge. The proposal builds strategically on current project discoveries and successes that comprehensively characterized patterns of real-world driving exposure and risk in 136 older drivers across 500,000 miles driven. Under the proposal's conceptual framework, functional abilities determine specific driver behavior patterns and errors. Behaviors, in tum, index driver functional abilities and clinical features of NIA-Alzheimer's Association (AA) core clinical criteria of mild cognitive impairment (MCI) and AD (operationalized by Alzheimer's clinical syndrome [ACS]). Sleep and mobility play roles as key mediators of relationships between driver behavior and functional impairment. Accordingly, our Specific Aims (SA) are: SA1) Extract key real-world driver behavior features over a continuous, 3-month, baseline period that classify normally aging, MCI, and ACS drivers by NIA-AA core clinical criteria. SA2) Determine the extent to which real-world driver sleep and mobility factors, collected over a continuous, 3-month baseline period, mediate the relationship between extracted driver behavior and clinical features (SA1). SA3) Develop models (statistical and supervised machine learning) that combine features of driver behavior (SA 1) and real-world sleep and mobility (SA2) to detect clinical feature severity of MCI and AD and predict disease progression. To address these aims, our team of experts-in medicine, AD, driving in aging and disease, cognitive neuroscience, transportation engineering, machine learning, computer vision, and longitudinal biostatistics--will apply our approach to drivers with a broader range of impairments across the aging to AD spectrum. A total of 180 drivers, ages 65- 90 years, who have ACS (N=40), MCI (N=80), or are normally aging (N=60) based on NIA-AA clinical criteria will be studied across a 3-month baseline period of real-world naturalistic driver behavior, sleep, and mobility monitoring. Two longitudinal assessments, each 1 year apart, will comprehensively assess each driver's risk for and severity of functional decline. By extracting "digital fingerprints" of aberrant driver behavior in drivers al risk for AD, this project complements seismic advances in biologic diagnosis of preclinical AD and advances NIH priorities lo improve older driver safely, mobility, quality of life...