Brief Cognitive Training for Mild Cognitive Impairment

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

Background: 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. Specific Aims: Aim 1: Determine the impact of a feasibility-focused five-session version compared to the full version of the ME-CCT-MCI on cognition, quality of life, daily functioning, mood, and caregiver burden. H1.1: Both the brief and full versions will have eligibility, acceptability, retention, and adherence rates similar to that seen in similar studies, as well as have low adverse effects and good reported participant satisfaction. H1.2: The brief version will yield benefits comparable to (not worse than) the full version of ME-CCT-MCI. H1.3: Benefits of intervention in both groups will be seen particularly in quality of life, activities of daily living, and caregiver burden. Within cognitive domains, though effects may not be strong, there will be particular benefit to learning and executive functioning compared to processing speed and language. Aim 2 (Exploratory): Investigate individual characteristics that predict cognitive benefits of intervention. Assess moderation effects of demographic factors, baseline cognitive scores, MCI subtype, and neuroimaging (Magnetic Resonance Imaging \[MRI\]) on predicting a greater benefit of intervention on cognition. H2.1: Participants with lower education levels and poorer baseline cognition will show less cognitive benefit from the interventions compared to those with higher education and better baseline performance. H2.2: Participants who have increased physical activity and better sleep at baseline will respond better to the intervention. H2.3: MCI subtype (amnestic or non-amnestic) will not differentially impact benefit of intervention. H2.4: Lower hippocampal volume will similarly be associated with reduced benefit to cognition compared to those with greater hippocampal volume.