Computerized Cognitive Remediation of Postviral Neurocognitive Dysfunction in Older Adults - Revised Abstract Section A significant minority of older adults display persistent cognitive impairments after the acute phase of a viral infection, referred to as Postviral Neurocognitive Dysfunction (PND). Underlying mechanisms remain poorly understood, though chronic neuroinflammation appears to reflect a key pathway. PND is debilitating, increases the risk for accelerated biological aging and dementia, and is associated with a substantial economic burden to society. Older adults are at heightened risk for PND given weakened immune systems, baseline age-related cognitive decline, and susceptibility to more severe acute viral illness. There is a critical lack of evidence-based treatments. The goal of this project is to determine the potential of a neuroplasticity-based computerized cognitive remediation (CCR) intervention for treating PND in older adults and probing underlying mechanisms. The proposed design is a randomized, two-arm, clinical trial pilot study. Older adults with PND (N = 75) will be assigned to a 6-week course of neuroplasticity-based CCR or an active, computer-based control condition. Specific aims are to: examine preliminary efficacy of CCR for improving cognitive performance and day-to-day functioning in older adults with PND (Aim 1); optimize and refine the CCR program for older adults with PND using iterative, data-driven, participatory design methodology (Aim 2); and determine if CCR reduces peripheral inflammation as a potential mechanism of clinical symptom relief (Exploratory Aim 3). The resultant data will guide a more definitive randomized controlled trial in PND via an R01. This K23 Career Development Award will provide the experience and training necessary for Dr. Lindbergh to achieve his long-term goal of becoming an independent investigator focused on developing neuroscience- informed behavioral treatments for late-life neurocognitive disorders. His plan for career development is organized around cultivating knowledge and skill in three primary areas: (1) development, administration, and evaluation of digital medicine technology; (2) clinical trial design, management, and data analysis; and (3) immunology, immune-inflammatory dysregulation, and blood-based inflammatory biomarkers. Dr. Lindbergh has assembled an outstanding mentorship team with expertise in each of these areas who will systematically evaluate his training progress and direct him through a robust curriculum of formal coursework, workshops, meetings, seminars, guided readings, and “hands-on” research experiences. The impressive infrastructure and multitude of resources available through the University of Connecticut Health Center—including the UConn Center on Aging, NIA-supported Claude D. Pepper Older Americans Independence Center, Psychiatry Department, Immunology Department, and Digital Media and Design Department—will provide the ideal scientific environment for Dr. Lindbergh to complete his training and transition to independence as a leading patient-oriented aging researcher.
