The Active Mind Trial: An Adaptive Randomized Trial to Improve Function and Delay Dementia

Study Overview
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Brief Summary
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Older adults at risk for dementia show a variety of cognitive deficits, which can be ameliorated by different cognitive training (CT) exercises. The best combination of CT exercises is unknown. The aim is to discover the most efficacious combination of CT exercises as compared to cognitive stimulation (which will serve as a stringent, active control) to modify the functional trajectories of older adults' with MCI, who are at high risk for dementia. The primary objective of the U01 phase was to design and pilot-test an adaptive, randomized clinical trial (RCT) of cognitive training (CT) combinations aimed to enhance performance of instrumental activities of daily living (IADL) among persons with mild cognitive impairment (MCI). In the R01 phase, the objective is to identify the best combination of CT exercises to delay dementia onset among persons with MCI. The longitudinal endpoint goal is reducing incident dementia. The primary aim of the study is to determine which CT combination has the best probability to delay dementia by producing the largest IADL improvements. The study further aims to explore neuroimaging and novel blood-based biomarkers.

Detailed Description
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An Adaptive Clinical Trial of Cognitive Training to Improve Function and Delay Dementia: The ACTIVE MIND Trial. In the U01 phase, the primary objective was to design and pilot-test an adaptive, randomized clinical trial (RCT) of cognitive training (CT) combinations aimed to enhance performance of instrumental activities of daily living (IADL) among persons with mild cognitive impairment (MCI). The longitudinal endpoint goal is delaying dementia onset. The secondary objectives of the U01 phase were: - To pilot test a plan to recruit and enroll under-represented minorities with the goal of obtaining a sample representative of the USF population in race and ethnicity. In the current R01 phase: The primary objective is to conduct an adaptive, randomized clinical trial (RCT) of cognitive training (CT) combinations aimed to enhance performance of instrumental activities of daily living (IADL) among persons with mild cognitive impairment (MCI). The longitudinal endpoint goal is reducing dementia incidence. Design: The design is an adaptive randomized trial to identify the best combination of CT exercises to improve IADL function and thereby delay dementia onset among persons with MCI. Four arms of CT will be compared to an active control condition. Outcomes: incident dementia is the primary outcome. Secondary outcome is Everyday Function: measures include Timed Instrumental Activities of Daily Living and iFunction. A composite of performance (measured by time and accuracy) will be derived. Interventions and Duration: Four combinations of computerized cognitive training and an active control computerized stimulation will be investigated. The five arms will be equivalent in terms of frequency and duration of each session (60 min/day, two-three days/wk, 16 weeks). Sample size: The study team plans to enroll up to 1305 participants. Individuals with a clinical diagnosis of MCI will be included in the study.

Official Title
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An Adaptive Clinical Trial of Cognitive Training to Improve Function and Delay Dementia: The ACTIVE MIND Trial

Conditions
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Age-related Cognitive Decline, Mild Cognitive Impairment, Dementia

Intervention / Treatment
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* Behavioral: Cognitive Training
* Behavioral: Computerized Cognitive Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 55 to 89 years of age Montreal Cognitive Assessment Score of 18-27 inclusive History of some change in cognitive function relative to established baseline and either 1) a CDR of 0.5; or 2) CDR of 0 and a clinical diagnosis of mild cognitive impairment (MCI) based on a multidisciplinary evaluation that included standardized neuropsychological testing If reports use of medications typically prescribed for dementia such as Namenda, Memantine, Namzaric, Donepezil, Aricept, Rivastigmine, Exelon, Razadyne, Galantamine, or Reminyl, dose has been stable for at least 30 days Adequate auditory capacity to understand normal speech. No greater than moderate hearing loss evident by thresholds less than or equal to 50 dB at 1000 and 2000 Hz in at least one ear determined by an audioscope. Adequate visual capacity to read from a computer screen at a normal viewing distance as measured by binocular visual acuity of 20/50 or better tested with a standard near visual acuity chart Reports and shows adequate motor capacity to touch a computer screen or control a computer mouse. Wiling to complete all study activities Willing and capable of providing informed consent Ability to understand study procedures and comply with them for the length of the study Exclusion Criteria: Currently enrolled in another randomized clinical trial, treatment trial, or another research study that assesses cognition Dementia diagnosis Clinical Dementia Rating Scale of 1 or greater History of large vessel stroke with significant residual motor or cognitive impairment History of moderate to severe traumatic brain injury with residual cognitive symptoms History of brain tumor Undergoing or plans to undergo surgery requiring anesthesia, chemotherapy, or radiation treatment in the six months following screening Congestive heart failure diagnosis Primary diagnosis of idiopathic Parkinson's disease Multiple sclerosis or Amyotrophic lateral sclerosis (ALS) diagnosis Evidence of a non-neurodegenerative neurological disorder that would interfere with the ability to carry out study activities. Evidence of any other unstable medical conditions that would interfere with the ability to carry out study activities or cause fluctuations in cognition (e.g., unstable diabetes, chronic obstructive pulmonary disorder dependent on oxygen) Geriatric Depression short scale score >5/15. Participants with mood disorders that are treated and stable and have a GDS score < 6/15 are not excluded. Any other clinically significant or unstable medical condition (e.g., ongoing alcohol dependency or drug abuse, schizophrenia, psychosis) that in the assessor's opinion would interfere with the ability to carry out study activities. Previous participation in 10 or more hours of a computerized cognitive intervention program in the past two years Previous participation in cognitive intervention research at the study site in the past 2 years Planning on going away or being otherwise unavailable for a period of more than three weeks in the six months following screening Contraindications to MRI such as pacemaker, metal implants in body, or claustrophobia

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CTa<br>Participants will complete computerized cognitive training. The duration is 60 min/day; the frequency is two to three days/wk, for 16 weeks with the goal of completing 40 sessions. | Behavioral: Cognitive Training<br>* Participants will be completing a total of 40 computerized sessions.<br>|
| Experimental: CTab<br>Participants will complete computerized cognitive training. The duration is 60 min/day; the frequency is two to three days/wk, for 16 weeks with the goal of completing 40 sessions. | Behavioral: Cognitive Training<br>* Participants will be completing a total of 40 computerized sessions.<br>|
| Experimental: CTac<br>Participants will complete computerized cognitive training. The duration is 60 min/day; the frequency is two to three days/wk, for 16 weeks with the goal of completing 40 sessions. | Behavioral: Cognitive Training<br>* Participants will be completing a total of 40 computerized sessions.<br>|
| Experimental: CTabc<br>Participants will complete computerized cognitive training. The duration is 60 min/day; the frequency is two to three days/wk, for 16 weeks with the goal of completing 40 sessions. | Behavioral: Cognitive Training<br>* Participants will be completing a total of 40 computerized sessions.<br>|
| Active Comparator: Computerized Cognitive Stimulation<br>Participants will complete cognitively-stimulating computer activities. The duration is 60 min/day; the frequency is two to three days/wk, for 16 weeks with the goal of completing 40 sessions. | Behavioral: Computerized Cognitive Stimulation<br>* Participants will be completing a total of 40 computerized cognitive stimulation sessions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dementia incidence | Clinical diagnosis of dementia | At follow-up visit between 6 months to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Useful Field of View Test performance overall score | Useful Field of View test (UFOV) score across three subtests measured in milliseconds (ms). Lower scores are better. | change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months | 
| Graduated continuous performance test score | The metrics of performance are target accuracy (in percent correct) and the variability of responses (standard deviation of response times to target images). Higher scores are better. | change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months | 
| Examiner Executive Function Set shifting, Anti-Saccades, and Flanker performance composite score | The proprietary software calculates an overall executive function composite score using item response theory. Higher scores are better | change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months | 
| Timed IADL performance score | A composite z score is calculated that reflects the overall time and accuracy of performance on the Timed IADL subtests per standard, published procedures (SPSS syntax of scoring method can be provided). Lower scores are better. | change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months | 
| ifunction performance efficiency index | An overall score reflecting time and accuracy (i.e., efficiency index) is calculated to reflect performance across the ifunction subtests the proprietary software determines the score. Higher scores are better for efficiency index | change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months |