Clinicopathologic Factors Associated With Reversion to Normal Cognition in Patients With Mild Cognitive Impairment

Background and Objectives To identify clinicopathologic factors contributing to mild cognitive impairment (MCI) reversion to normal cognition. Methods We analyzed 3 longitudinal cohorts in this study: the Mayo Clinic Study of Aging (MCSA), the Religious Orders Study and Memory and Aging Project (ROSMAP), and the National Alzheimer's Coordinating Center (NACC). Demographic characteristics and clinical outcomes were compared between patients with MCI with or without an experience of reversion to normal cognition (referred to as reverters and nonreverters, respectively). We also compared longitudinal changes in cortical thickness, glucose metabolism, and amyloid and tau load in a subcohort of reverters and nonreverters in MCSA with MRI or PET imaging information from multiple visits. Results We identified 164 (56.4%) individuals in MCSA, 508 (66.8%) individuals in ROSMAP, and 280 (34.1%) individuals in NACC who experienced MCI reversion to normal cognition. Cox proportional hazards regression models showed that MCI reverters had an increased chance of being cognitively normal at the last visit in MCSA (HR 3.31, 95% CI 2.14-5.12), ROSMAP (HR 3.72, 95% CI 2.50-5.56), and NACC (HR 9.29, 95% CI 6.45-13.40) and a reduced risk of progression to dementia (HR 0.12, 95% CI 0.05-0.29 in MCSA; HR 0.41, 95% CI 0.32-0.53 in ROSMAP; and HR 0.29, 95% CI 0.21-0.40 in NACC). Compared with MCI nonreverters, reverters had better-preserved cortical thickness (beta = 0.082, p <0.001) and glucose metabolism (beta = 0.119, p = 0.001) and lower levels of amyloid, albeit statistically nonsignificant (beta = -0.172, p = 0.090). However, no difference in tau load was found between reverters and nonreverters (beta = 0.073, p = 0.24). Discussion MCI reversion to normal cognition is likely attributed to better-preserved cortical structure and glucose metabolism.