The goal of this clinical trial is to develop a five-week virtual cognitive training intervention for people with Mild Cognitive Impairment (MCI) based off an existing eight-week intervention. The main question it aims to answer is:

• Is five weeks of training as good as eight weeks in improving cognition, quality of life, daily functioning, and mood, and in reducing caregiver burden? Researchers will compare five weeks of cognitive training to eight weeks of training to see if the shorter version is as effective as the full training.

Participants will complete all activities virtually:

• Complete a screening visit with a study partner (typically a family member, roommate, or close friend) to determine eligibility to participate in the study
• Complete some tests of memory and thinking and some questionnaires
• Attend weekly two-hour group cognitive training sessions with a trained group leader, for five or eight weeks
• Redo the questionnaires and tests of memory and thinking immediately after completing the training, and three months after completing the training

The purpose of this project is to assess the efficacy of brief and full compensatory cognitive training protocols in people diagnosed with Mild Cognitive Impairment (MCI), a state often thought of as a transitory stage between normal aging and dementia. According to the Alzheimer's Association, one in three older adults dies with Alzheimer's disease or another dementia. In 2024, Alzheimer's disease and other dementias were estimated to cost approximately $360 billion, and these costs are only expected to grow, with estimates rising over $1 trillion by 2050. Research on dementia interventions is growing, with research on neurotransmitter augmentation showing cognitive improvement, and more recently, brain stimulation showing gains in memory and general cognition. However, brain stimulation is not yet approved by the U.S. Food and Drug Administration, and eligibility for anti-amyloid medications is restricted to patients with Alzheimer's Disease pathology and low risk profiles, severely limiting accessibility for many patients. Cognitive rehabilitation is a low-cost solution that is not restricted to patients meeting certain requirements or with a specific etiology and can be utilized by any trained clinician.

Cognitive training and rehabilitation is typically categorized as either restorative or compensatory. Restorative training involves repetitive tasks targeting specific cognitive domains (e.g., attention, memory) by harnessing the brain's plasticity and is often completed via computer-based exercises, but often lacks generalizability. Compensatory rehabilitation focuses on individualized strategies that use alternative cognitive processes and supportive aids to compensate for impairment rather than improving it. Cognitive training generally improves quality of life more than pharmacological treatments, and cognitive rehabilitation is particularly effective at improving functional ability and reducing caregiver burden.

Cognitive Symptom Management and Rehabilitation Therapy (CogSMART) is a compensatory cognitive training program which uses cognitive strategies to improve cognition and daily functioning. Originally developed for veterans with traumatic brain injury, it includes a publicly available manual for people with MCI called Motivationally Enhanced Compensatory Cognitive Training for MCI (ME-CCT-MCI), which has shown effectiveness in improving functional ability. This program consists of eight two-hour sessions delivered once per week over eight weeks. However, approximately 74% of providers report modifying CogSMART by combining, modifying, or omitting exercises. Despite this, no research to date has examined the effectiveness of an abbreviated version, though evidence from shorter-term psychotherapy suggests it is not significantly less effective than longer-term approaches. This study will develop and implement a five-session version of ME-CCT-MCI, to reduce time burdens and increase accessibility, feasibility, and adherence for patients, caregivers, and providers.

This proposal advances current science in several ways. First, it further validates the ME-CCT-MCI manual. Though extensive research supported the development of this manual, there has been only one randomized controlled trial validating its use, and only a small number of studies that have since validated its use outside of a Veterans Affairs setting. Of these studies, only two include an assessment of effects on cognition, one of which cites the Indian Adapted ME-CCT-MCI, and the other uses a similar manual adapted for addictions, with no study validating the original manual's effect on cognition. Second, creating and testing a brief version of this manual allows for improved accessibility and feasibility, reducing the risk of dropout. Third, the use of an extensive neuropsychological battery (the National Alzheimer's Coordinating Center Uniform Data Set [NACC-UDS]) allows assessment of improvement in specific cognitive domains. Though the randomized controlled trial did assess effects on objective cognition, it found only a nonsignificant trend and assessed general cognition rather than specific domains. Other research has shown that compensatory cognitive rehabilitation is beneficial to cognition, but there is less clear evidence of the specific pattern of effect on cognitive domains, which may help inform clinical decision making in determining which patients may benefit the most from this intervention. Fourth, this study will investigate what participant factors (i.e., education, baseline cognition, lifestyle, and hippocampal volume) predict benefit of intervention, further determining which patients may benefit from this intervention and contributing to future development of personalized medicine.

Inclusion Criteria:

• 65 years of age or older, less than 85 years
• Have the ability to speak and understand English
• Time and willingness to commit to the completion of this study
• Availability of a study partner (typically a relative, spouse, offspring, or roommate) for initial and post-intervention testing
• A global Clinical Dementia Rating scale (CDR) score of 0.5 and cognitive performance of <26 on the Montreal Cognitive Assessment (MoCA) or <19 on the MoCA-BLIND for categorization of MCI, as determined in the screening appointment.

Exclusion Criteria:

• Self-reported diagnosis of dementia or functional impairment that requires assistance
• Recent changes in medications for memory (i.e., prescribed or changed medications for memory within 30 days)
• Major psychiatric illness (schizophrenia, current substance dependence, or undertreated depression or anxiety), or 15-item Geriatric Depression Scale (GDS-15) score of eight or higher
• Hearing, vision, or motor deficits that would interfere with standardized cognitive assessment or participation in study interventions: e.g., inability to hear through headphones (with or without hearing aids). If vision is corrected with lenses to appropriate levels, then participant will be eligible
• No access to reliable, stable internet, OR
• Current participation in another cognitive training program or treatment study.

The cognitive assessment data will be deidentified and made publicly available upon study completion. Permission to disseminate the neuroimaging data to a larger audience has not been granted so this will not be included in the publicly available dataset.

A data dictionary will be available accompanying the cognitive assessment data. The manual for the compensatory training intervention (Motivationally Enhanced Compensatory Cognitive Training for Mild Cognitive Impairment) is already publicly available, and any changes made in this study to create a brief version will also be shared.

Code created to analyze the results data (in R, python, or MATLAB) will be cleaned for comprehension and shared to support replication.

Data will be made fully accessible after the study is completed and published, and before the PI (Cameron Perrin) has graduated in 2028. Open Science Framework is designed to support long-term preservation of research data, so the data will be accessible for as long as this service is available.

Access to this scientific data will not be controlled and will be made publicly available on Open Science Framework.