Cognitive Rehabilitation and Functional Outcomes in Long COVID–Related Cognitive Impairment

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Abstract
Importance: Cognitive impairment is common in long COVID and severely affects daily life, with no proven treatments to date. Objective: To evaluate the ability of cognitive rehabilitation (CR) to improve goal attainment, cognitive, and clinical outcomes in individuals with cognitive impairment as part of long COVID. Design, Setting, and Participants: This multicenter, single-blind, 2-arm, parallel-group randomized clinical trial was conducted at 3 sites in England between February 2023 and March 2024. Participants were adults aged 30 to 60 years with prior COVID-19 infection and objective cognitive impairment (≥1 SD below age norm in ≥2 cognitive domains). A sample size of 88 participants (44:44) was required to detect a conservative effect of 0.7 on the goal attainment score at 3 months. Interventions: Participants were randomized (1:1) to CR or treatment as usual (TAU). CR consisted of 10 individual 1-hour sessions conducted once per week with a trained researcher, applying evidence-based strategies to 3 individually selected, personally meaningful functional goals. TAU was variable, with most participants having access to specialist memory clinics. Main Outcome and Measures: The primary outcome consisted of participant-reported goal-attainment scores at 3 months after randomization measured by the Bangor Goal-Setting Interview. Analysis was conducted on an intention-to-treat basis using multilevel mixed-effects models with 2-sided 95% CIs and 5% significance. Results: A total of 78 participants (24 male [30.8%] and 54 female [69.2%]; mean [SD] age, 47.3 [7.2] years) were randomized, including 38 individuals in CR and 40 individuals in TAU groups. At 3 months after randomization, goal attainment was significantly greater in the CR compared with the TAU group (adjusted mean difference, 2.88 [95% CI, 2.03-3.73]; P < .001; Cohen d = 1.57), with CR providing a large and clinically meaningful treatment effect. This was sustained at 6 months, with a lower effect size (adjusted mean difference, 1.72 [95% CI, 0.86-2.57]; P < .001; Cohen d = 0.91). Conclusions and relevance: In this study, individualized, goal-oriented CR led to significant and sustained improvements in goal attainment in people with long COVID–related cognitive impairment. These findings may guide and inform the provision of CR treatments and services for people living with long COVID. Trial Registration: ClinicalTrials.gov Identifier: NCT05731570

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