Cognitive Remediation

Cutter Lindbergh

Status

Enrolling

Conditions

Postviral Syndrome

Aging

Inflammation

Cognitive Dysfunction

Cognitive Remediation

Digital Medicine

Treatments

Other: Computerized Cognitive Remediation

Other: Alternative Computer Activities

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT07171450

1K23AG086612-01A1 (U.S. NIH Grant/Contract)

25-389-2

Details and patient eligibility

About

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)

Full description

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).

Enrollment

75 estimated patients

Sex

All

Ages

60+ years old

Volunteers

No Healthy Volunteers

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
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