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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
75
The computerized cognitive remediation intervention ("NeuroFlex") consists of a series of gamified tasks administered via computer tablet. The intervention provides both "bottom up" training to improve basic processing of sensory stimuli and "top down" training to improve executive functions. Importantly, NeuroFlex personalizes gameplay with adaptive algorithms that adjust difficulty on a trial-by-trial basis. Participants are prescribed a 30-hour dose distributed across 6 weeks. The treatment is completed remotely by the participant within their own home or other private location that is most convenient for the participant.
The active control condition is carefully matched to the experimental condition in duration, computer tablet use, audiovisual stimulation, reward presentation, and interaction with study staff. It involves playing visuospatially-oriented computerized games that do not load on executive functions and watching stimulating educational videos.
UConn Health
Farmington, Connecticut, United States
RECRUITINGGroup Difference in Set-Shifting Abilities at Post-Treatment as Measured with Trails B
Part B of the Trail Making Test (Trails B) is an executive functioning measure of set-shifting abilities in which the examinee must rapidly alternate between connecting numbers and letters distributed across a page. The total time (in seconds) required for the examinee to complete the task is recorded. Lower scores (in seconds) indicate better performance. Time to complete Trails B at the post-treatment visit will be compared between treatment groups (i.e., NeuroFlex vs. Active Control Condition), controlling for pre-treatment Trails B performance.
Time frame: Pre-treatment and post-treatment (Week 7)
Group Difference in Set-Shifting Abilities at 6 Months as Measured with Trails B
Part B of the Trail Making Test (Trails B) is an executive functioning measure of set-shifting abilities in which the examinee must rapidly alternate between connecting numbers and letters distributed across a page. The total time (in seconds) required for the examinee to complete the task is recorded. Lower scores (in seconds) indicate better performance. Time to complete Trails B at the 6-month visit will be compared between treatment groups (i.e., NeuroFlex vs. Active Control Condition), controlling for pre-treatment Trails B performance.
Time frame: Pre-treatment and 6 Months
User Experience/Interface with Computerized Cognitive Remediation Program at Post-Treatment as Measured with the System Usability Scale
The System Usability Scale is a well-validated, 10-item, self-report questionnaire of user experience/interface (UX/ UI) with computer-based programs. Participants rate each item using a 5-point Likert-style scale with response options ranging from "Strongly Disagree" to "Strongly Agree". Total scores ranging from 0-100 are calculated using a standard equation. Higher total scores indicate better UX/UI.
Time frame: Post-Treatment (Week 7)
Group Difference in Inhibitory Control at Post-Treatment as Measured with the Stroop Color and Word Test
The Stroop Color and Word Test is an executive functioning measure of inhibitory control in which the examinee is presented with a sheet containing words of various colors printed in discordant ink colorings. The examinee is instructed to rapidly name the color of the ink that the words are printed in without reading the printed word (i.e., the prepotent response must be inhibited). An interference score is calculated by determining how many items the examinee completes within a set period of time, subtracting out their performance on baseline conditions (without an interference component) to control for processing speed. Higher scores indicate better performance. The score at the post-treatment visit will be compared between treatment groups (i.e., NeuroFlex vs. Active Control Condition), controlling for pre-treatment performance.
Time frame: Pre-treatment and post-treatment (Week 7)
Group Difference in Inhibitory Control at 6 Months as Measured with the Stroop Color and Word Test
The Stroop Color and Word Test is an executive functioning measure of inhibitory control in which the examinee is presented with a sheet containing words of various colors printed in discordant ink colorings. The examinee is instructed to rapidly name the color of the ink that the words are printed in without reading the printed word (i.e., the prepotent response must be inhibited). An interference score is calculated by determining how many items the examinee completes within a set period of time, subtracting out their performance on baseline conditions (without an interference component) to control for processing speed. Higher scores indicate better performance. The score at the 6-Month visit will be compared between treatment groups (i.e., NeuroFlex vs. Active Control Condition), controlling for pre-treatment performance.
Time frame: Pre-treatment and 6 months
Group Difference in Verbal Generativity, Initiation, and Strategy Use at Post-Treatment as Measured with the Controlled Oral Word Association Test (COWAT)
The COWAT is an executive functioning measure of verbal generativity, initiation, and strategy use in which the examinee must quickly generate as many words as possible, within a set period of time, according to pre-specified rules (e.g., words starting with a certain letter of the alphabet). A total score is calculated by adding up the number of words that were correctly produced within the time limit. Higher total scores indicate better performance. The score at the post-treatment visit will be compared between treatment groups (i.e., NeuroFlex vs. Active Control Condition), controlling for pre-treatment performance.
Time frame: Pre-treatment and post-treatment (Week 7)
Group Difference in Verbal Generativity, Initiation, and Strategy Use at 6 Months as Measured with the Controlled Oral Word Association Test (COWAT)
The COWAT is an executive functioning measure of verbal generativity, initiation, and strategy use in which the examinee must quickly generate as many words as possible, within a set period of time, according to pre-specified rules (e.g., words starting with a certain letter of the alphabet). A total score is calculated by adding up the number of words that were correctly produced within the time limit. Higher total scores indicate better performance. The score at the 6-month visit will be compared between treatment groups (i.e., NeuroFlex vs. Active Control Condition), controlling for pre-treatment performance.
Time frame: Pre-treatment and 6-months
Group Difference in Attention-Related Problems at Post-Treatment as Measured with the Conners Continuous Performance Test
The Conners Continuous Performance Test (Conners CPT) is a computerized measure of attention-related problems in which isolated letters are flashed briefly on a computer screen. The examinee is instructed to respond (by keypress) as quickly as possible whenever any letter appears on the screen, except for when the non-target letter appears. A summary measure of attention can be calculated based on the examinee's performance over the course of the test. The score at the post-treatment visit will be compared between treatment groups (i.e., NeuroFlex vs. Active Control Condition), controlling for pre-treatment performance.
Time frame: Pre-treatment and post-treatment (Week 7)
Group Difference in Attention-Related Problems at 6 Months as Measured with the Conners Continuous Performance Test
The Conners Continuous Performance Test (Conners CPT) is a computerized measure of attention-related problems in which isolated letters are flashed briefly on a computer screen. The examinee is instructed to respond (by keypress) as quickly as possible whenever any letter appears on the screen, except for when the non-target letter appears. A summary measure of attention can be calculated based on the examinee's performance over the course of the test. The score at the 6-month visit will be compared between treatment groups (i.e., NeuroFlex vs. Active Control Condition), controlling for pre-treatment performance.
Time frame: Pre-treatment and 6-months
Group Difference in Subjective Cognitive Concerns at Post-Treatment as Measured with the Everyday Cognition Scale (ECog)
The ECog is a self-report questionnaire of subjective cognitive concerns covering various domains, including memory, language, visuospatial skills, planning, organization, and divided attention. It uses a Likert-style scale ranging from 1-4, where 1 is "better or no change" and 4 is "consistently much worse" compared to prior. A total score, the average of all completed items ranging from 1 to 4, can be calculated to provide a global index of subjective cognitive concerns across domains. Lower total scores indicate better everyday cognitive functioning. The score at the post-treatment visit will be compared between treatment groups (i.e., NeuroFlex vs. Active Control Condition), controlling for pre-treatment performance.
Time frame: Pre-treatment and post-treatment (Week 7)
Group Difference in Subjective Cognitive Concerns at 6 Months as Measured with the Everyday Cognition Scale (ECog)
The ECog is a self-report questionnaire of subjective cognitive concerns covering various domains, including memory, language, visuospatial skills, planning, organization, and divided attention. It uses a Likert-style scale ranging from 1-4, where 1 is "better or no change" and 4 is "consistently much worse" compared to prior. A total score, the average of all completed items ranging from 1 to 4, can be calculated to provide a global index of subjective cognitive concerns across domains. Lower total scores indicate better everyday cognitive functioning. The score at the 6-month visit will be compared between treatment groups (i.e., NeuroFlex vs. Active Control Condition), controlling for pre-treatment performance.
Time frame: Pre-treatment and 6-months
Group Difference in Functional Disability at Post-Treatment as Measured with the World Health Organization Disability Assessment Schedule (WHODAS)
The WHODAS is a 36-item assessment instrument that measures functional disability in multiple domains, including cognition, mobility, selfcare, getting along (i.e., interacting with others), life activities, and participation (e.g., joining in community and societal activities). A summary score, ranging from 0 to 100, can be calculated that provides a measure of overall functioning across domains. Higher summary scores correspond to greater levels of functional disability. The score at the post-treatment visit will be compared between treatment groups (i.e., NeuroFlex vs. Active Control Condition), controlling for pre-treatment performance.
Time frame: Pre-treatment and post-treatment (Week 7)
Group Difference in Functional Disability at 6 Months as Measured with the World Health Organization Disability Assessment Schedule (WHODAS)
The WHODAS is a 36-item assessment instrument that measures functional disability in multiple domains, including cognition, mobility, selfcare, getting along (i.e., interacting with others), life activities, and participation (e.g., joining in community and societal activities). A summary score, ranging from 0 to 100, can be calculated that provides a measure of overall functioning across domains. Higher summary scores correspond to greater levels of functional disability. The score at the 6-month visit will be compared between treatment groups (i.e., NeuroFlex vs. Active Control Condition), controlling for pre-treatment performance.
Time frame: Pre-treatment and 6-months
Group Difference in Episodic Memory at Post-Treatment as Measured with the California Verbal Learning Test (CVLT)
The CVLT is a test of episodic memory that assesses the examinee's ability to learn and recall a list of words. The number of words correctly recalled after a delay period is measured (Long Delay Free Recall). Higher scores (i.e., more words recalled) correspond to better memory performance. The score at the post-treatment visit will be compared between treatment groups (i.e., NeuroFlex vs. Active Control Condition), controlling for pre-treatment performance.
Time frame: Pre-treatment and post-treatment (Week 7)
Group Difference in Episodic Memory at 6 Months as Measured with the California Verbal Learning Test (CVLT)
The CVLT is a test of episodic memory that assesses the examinee's ability to learn and recall a list of words. The number of words correctly recalled after a delay period is measured (Long Delay Free Recall). Higher scores (i.e., more words recalled) correspond to better memory performance. The score at the 6-month visit will be compared between treatment groups (i.e., NeuroFlex vs. Active Control Condition), controlling for pre-treatment performance.
Time frame: Pre-treatment and 6-months
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