CoMTAD: Cognitive Monitoring during Treatment for Alzheimer disease

About This Grant

PROJECT SUMMARY There are now anti-amyloid therapies available to slow the clinical progression of Alzheimer’s disease (AD). These therapies come with the risk of negative side-effects including amyloid related imaging abnormalities (ARIA). Little is known about acute and long-term cognitive consequences of ARIA events given the expense and staff / patient burden associated with the imaging scans that are currently used to detect ARIA. Neuropsychological tests are frequently leveraged to provide an assessment of neurological integrity at very low cost. Nevertheless, because it is unknown precisely when an ARIA event may occur, cognitive testing would need to be relatively frequent, producing substantial burden on patients and clinical staff. The Cognitive Monitoring during Treatment for Alzheimer disease (CoMTAD) study aims to address these difficulties by developing and validating a cognitive safety monitoring system to detect adverse side effects of anti-amyloid therapy. We will administer an extremely brief, but well-validated, digital cognitive assessment using the Ambulatory Research in Cognition (ARC) smartphone platform, up to three times per week for approximately thirty weeks. Patients will be classified as having ARIA or not based on imaging findings. We will utilize changepoint models to evaluate if there are acute or long-term changes in cognition associated with incidence of ARIA. Cognitive consequences of ARIA may not manifest as a sudden drop in performance but rather a more subtle change in variability in cognitive scores across days. The high-frequency (3 times per week) assessment strategy of CoMTAD will afford the ability to examine these additional metrics. The ARC platform is uniquely suited for this purpose as it has already been extensively validated in a healthy older adult and symptomatic AD population. The ARC tasks have been specifically designed to be sensitive to cognitive change in this population and are well-tolerated by the majority of participants. Moreover, because ARC is administered remotely, it can be deployed at scale to patients regardless of their proximity to a major medical center. The ultimate goal of the study will be to provide easy to obtain, cost effective, cognitive safety monitoring information to medical providers so they can determine if a patient is experiencing an adverse neurological episode prior to an expensive and relatively burdensome MRI scan. Given the lack of cerebrospinal fluid or blood-based biomarkers of ARIA, we consider the CoMTAD study to provide an essential tool for physicians to track cognitive health of patients undergoing these novel therapies. This goal will be furthered by our secondary in-lab sleep restriction study. A group of volunteers will undergo 24-hours of sleep restriction to track how performance on ARC declines with increasing sleep deprivation. This will provide benchmarks for physicians to determine if declines in performance are clinically important.