Cognitive Remediation

Computerized Cognitive Remediation of Postviral Neurocognitive Dysfunction in Older Adults

The goal of this clinical trial is to determine if a neuroscience-based computerized cognitive remediation ("brain training") program can treat neurocognitive dysfunction (i.e., memory or thinking difficulties) that emerges in some older adults following a viral infection. The main questions it aims to answer are:

• Does computerized cognitive remediation improve cognitive performance and day-to-day functioning in older adults with postviral neurocognitive dysfunction?
• Will treatment effects be maintained over time, leading to better long term cognitive outcomes?
• Does the treatment lead to reductions in blood-based markers of inflammation as a potential mechanism of cognitive symptom improvement?
• Can the treatment be optimized and refined based on feedback from participants to improve user (patient) experience? Researchers will compare the computerized cognitive remediation program to an active computer-based control condition (alternative computer activities) to see if the computerized cognitive remediation program works to treat postviral neurocognitive dysfunction.

Participation takes approximately 43-48 hours over 7 months, with most activities (40-46 hours) completed within the first 7-8 weeks, including:

• Initial intake visit: Eligibility confirmation (~2-3 hours)
• Computer activities: About 5 hours per week for ~6 weeks (total ~30 hours) completed on a computer tablet provided by the study and loaned to participants for use during the treatment phase
• Weekly remote check-in meetings: ~30 minutes each during treatment
• Blood draws: Two sessions (before and after treatment), ~20-30 minutes each
• Three research visits: Pre-treatment, post-treatment, and 6-month follow-up (~2-3 hours each, including assessments of cognitive, emotional, and daily functioning)

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).

Inclusion Criteria:

• age ≥ 60 years old
• prior history of COVID-19 that was confirmed with viral testing (e.g., positive laboratory test or positive at-home rapid test)
• cognitive symptoms (e.g., memory or thinking concerns) following COVID- 19 infection that have lasted for at least 12 weeks and are still present
• clinically meaningfully subjective cognitive concerns (i.e., T-score < 40) on the PROMIS-Cognitive Function Scale
• objective evidence of cognitive decline*, as defined by performance on standardized measures of executive functioning, memory, or processing speed from the NIH Toolbox Cognition Battery that is at least 1 standard deviation below estimated premorbid cognitive functioning [*at least one third of the sample, or 25 out of 75 subjects, will be required to meet this inclusion criterion]
• fluent in English language
• off psychiatric medication or on a stable dose for at least 8 weeks

Exclusion Criteria:

• history of neurological disorder with potential to interfere with study participation or confound results (e.g., uncontrolled seizure disorder, moderate to severe traumatic brain injury or stroke with persistent neurological deficits)
• history of dementia and/or dementia range performance on the Mini- Mental State Examination (i.e., score of less than or equal to 23)
• prior diagnosis of Mild Cognitive Impairment (MCI) or Mild Neurocognitive Disorder unrelated to the participant's history of COVID-19
• history of severe psychiatric illness that may interfere with study participation or confound results (e.g., bipolar disorder, schizophrenia, or other psychotic disorder)
• history of significant neurodevelopmental condition that may interfere with study participation or confound results (e.g., intellectual disability, autism spectrum disorder, or specific learning disorder with impairment in reading)
• alcohol or other substance use disorder within the past 2 years
• significant sensory impairments (e.g., blindness) that would interfere with the ability to complete neuropsychological measures or engage in the tablet-based intervention
• performance that is below expectation on a test of effort and validity