Purpose Long COVID brain fog is often disabling. Yet, no empirically-supported treatments exist. This study’s objectives were to evaluate feasibility and efficacy, provisionally, of a new rehabilitation approach, Constraint-Induced Cognitive Therapy (CICT), for post-COVID-19 cognitive sequelae.

Design Sixteen community-residents ≥ 3-months post-COVID-19 infection with mild cognitive impairment and dysfunction in instrumental activities of daily living (IADL) were enrolled. Participants were randomized to Immediate-CICT or treatment-as-usual (TAU) with crossover to CICT. CICT combined behavior change techniques modified from Constraint-Induced Movement Therapy with Speed of Processing Training, a computerized cognitive-training program. CICT was deemed feasible if (a) ≥80% of participants completed treatment, (b) the same found treatment highly satisfying and at most moderately difficult, and (c) <2 study-related, serious adverse-events occurred. The primary outcome was IADL performance in daily life (Canadian Occupational Performance Measure). Employment status and brain fog (Mental Clutter Scale) were also assessed.

Results Fourteen completed Immediate-CICT (n=7) or TAU (n=7); two withdrew from TAU before their second testing session. Completers were [M (SD)]: 10 (7) months post-COVID; 51 (13) years old; 10 females, 4 males; 1 African American, 13 European American. All the feasibility benchmarks were met. Immediate-CICT, relative to TAU, produced very large improvements in IADL performance (M=3.7 points, p<.001, d=2.6) and brain fog (M=-4 points, p<.001, d=-2.9). Four of five non-retired Immediate-CICT participants returned-to-work post-treatment; no TAU participants did, p=.048.

Conclusions CICT has promise for reducing brain fog, improving IADL, and promoting returning-to-work in adults with Long COVID. Findings warrant a large-scale RCT with an active-comparison group.

IMPACT

Brain fog in adults with Long COVID is often associated with dysfunction in everyday activities and unemployment. Yet, there are no empirically supported treatments targeting cognition in this population. Findings from this small-scale, pilot randomized controlled trial (RCT) suggest that a novel intervention, i.e., Constraint-Induced Cognitive Therapy, is a feasible cognitive rehabilitation method in adults with Long COVID cognitive sequelae with promise of (a) improving performance of cognition-based tasks in daily life and (b) promoting return-to-work. Further studies with larger sample sizes are warranted.

Speed of Processing Training (SOPT) has been shown to increase processing speed in older adults without neurological disorders but has not been applied to adults with brain fog due to Long COVID, in whom slowing of cognitive processing speed is common. The results of this pilot RCT suggest that SOPT, in conjunction with behavior change techniques, may increase cognitive processing speed in this brain-injured population.

Posit Science donated Speed of Processing Training (SOPT) software for use in another study directed by authors GU and KB. This software was not used in this study. No restrictions on the publication or interpretation of the data from this or any other study were attached to the donation. KB serves on the Scientific Advisory Board of Posit Science, and has received travel support from Posit Science, and serves as a consultant for Posit Science. None of these activities or renumeration were for this study.

NCT04644172

The conduct of this study was supported by intramural funds from the UAB Department of Psychology and UAB Integrative Center for Aging Research, and by a Scholar Award from the National Institutes of Health (NIH) National Rehabilitation Research Resource to Enhance Clinical Trials (P2CHD086951). Preparation of the manuscript was supported by grant 90IFRE0073 from the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR).

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IRB of the University of Alabama at Birmingham gave approval for this work

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