Cognitive Rehabilitation for Post-COVID-19 Cognitive Impairment

Assessing the Effectiveness of Cognitive Rehabilitation for Post-COVID-19 Cognitive Impairment: A Pilot Study

This pilot randomized controlled trial is to investigate the feasibility and efficacy of cognitive rehabilitation for patients with post-COVID-19 cognitive impairment. Additionally, the study will obtain preliminary data, using rsfMRI, regarding the potential underlying connectivity networks, mediating the effect of CR on cognitive improvements.

Active Group participants will receive nine 1.5-h sessions of virtual (via Zoom platform) group-based training, three individual virtual 1-h training sessions, and approximately 20 h of home practice and CCT over 12 weeks.

The control group format will be twelve 1.5 or 1 h virtual sessions over 12 weeks, in addition to 20 h of home practice of a computerized control program (e.g., consisting of publicly available computer games such as sudoku and crossword puzzles).

The virtual small group format will include two to five participants and one facilitator per group. The three individual sessions are distributed at the beginning, middle, and towards the end of the training program. Individual Session 1 occurs after Group Session 1. It covers orientation to the training program, including orientation to and clarification of the Participant Handbook. Individual Session 2 occurs after Group Session 5 and involves review and implementation of training strategies. Individual Session 3 occurs after Group Session 9 and covers review of learned strategies, implementation of training strategies in daily life, and review of execution, obstacles, and adjustments required for individual projects.

The active control group will control for non-specific effects inherent to supervised CR. Participants will receive a manualized brain health education (BHE) training program, matched with the adapted CR intervention for therapist time and homework. Once these participants complete the 12 weeks of the control intervention and undergo the post-intervention assessments, participants will be offered the 12 weeks active intervention to ensure that all study participants have the potential of benefitting from CR.

Trail Making Test - Part B: a measure of aspects of executive functioning (e.g., set- shifting and cognitive flexibility), where participants connect the dots on a page scattered with numbers and letters in alternating sequence. Scored by time in seconds. Higher number of seconds implies deficiencies in cognitive functioning.

Wisconsin Card Sorting Task (WCST)-64: Computer Version 2. The WCST-64 is a measure of executive functioning assessing novel problem solving and abstract thinking. The software scores the test and generates percentile scores (0-100). Scored by percentile. Higher percentile implies scoring better than others who have completed the task.

Acceptability: using 7 Likert-rated items (scores will be coded as: Low: ≤3; Moderate: 3-3.9; Good: ≥4). Full range from 1-7, with higher score indicating higher acceptability.

Open-ended questions to staff regarding challenges conducting intervention (e.g., difficulty enrolling, reaching, engaging participants; scores will be coded as: Low: <50%; Moderate: 50-70%; Good: >70%).

Participants' beliefs about how likely they are to benefit from the intervention using the Treatment Credibility and Expectancy Questionnaire. Full scale from 0-10, with higher score indicating higher treatment expectancy.

Neuroimaging Outcomes: Resting state functional connectivity (rsFC) within the central executive network (CEN).

Participants hear digit sequences of increasing lengths and have to recall them forward and in reversed order. Each level contains two equal number series with different numbers. Max score is 14 points for forward span and 14 points for backwards span. Higher score indicates better performance.

Single digits are presented every 3 seconds and the participant must add each new digit to the one immediately prior to it. The score is the total number correct out of 60 possible answers. Full scale range from 0-60. Higher scores represent better performance.

Requires participants to connect numbered dots in order as quickly as possible. A higher number of seconds implies worse performance.

Requires an individual to substitute digits for abstract symbols using a reference key as quickly as possible. Reaction times in seconds for the performance of the symbol-digit modalities test. A higher number of seconds implies worse performance.

A list learning task that assesses learning (immediate recall) and memory (delayed recall) and recognition discrimination. The total score (higher score means a better outcome) is converted to a standardized "T" score using normative data. The possible "T" score for each participant ranges from 20 to 80, with higher scores indicative of better performance.

Requires participants to name as many words as they can beginning with a particular letter in 60 seconds, and then as many animals as they can, respectively. A higher number of words or animals named is indicative of better performance.

The MINT is a research measure intended to assess word retrieval deficits. It requires participants to name a series of individually presented line drawings that range from highly common (e.g. butterfly) to more obscure (e.g., axle) objects. The total scores range from 0 to 32, with higher scores indicating better performance.

A measure of premorbid intellectual estimate. Scores range from 0-70, where a higher score indicates greater premorbid intellectual ability.

Inclusion Criteria: Adults ≥18 years of age Have a confirmed SARS-CoV-2 infection (positive PCR or are serum antibody positive [against spike protein if unvaccinated or N-capsid peptide if vaccinated]) Speak English Have objective mild to moderate cognitive impairment, which will be defined as impairment in executive function (a z-score >1.5 standard deviations below the normative mean) and in at least one other cognitive domain Endorse comfort and familiarity with technology. Exclusion Criteria: No method of contact Major neurocognitive disorder, as defined by a score <17 on the Montreal Cognitive Assessment (MoCA) History of pre-COVID-19 neurologic disease (e.g., stroke) History of severe head injury (as defined by loss of consciousness >30 minutes) Ongoing substance use disorder (Mini International Neuropsychiatric Interview Version 7.0.2 [MINI] or Alcohol Use Disorders Test-Consumption [AUDIT-C] >8) Unstable medical, neurologic, or psychiatric conditions precluding participation in research activities, and Contraindication for MRI (e.g., metallic/electronic implants). Not involved in cognitive rehabiliation/training or daily meditative practices during study enrollment

Anyone who wishes to access the data. Any purpose. Data are available indefinitely at (Link to be included in the URL field below).