Plasticity-based Adaptive Cognitive Remediation for Alzheimer Disease

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the effects of the experimental treatment (cognitive training) further outlined in this protocol on the cognitive abilities (e.g., processing speed, attention, working memory, and executive function), brain functionality, functional status and quality of life of individuals with age-related cognitive decline as compared to a computer-based active control.

Detailed Description
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The normal aging has a devastating effect on our cognitive ability to learn and remember, on the speed with which the investigators process information, and on our ability to reason. By 2050, nearly 14 million individuals in the US will be living with Alzheimer's disease (AD), up from 5 million in 2013. AD is the most common cause of dementia, resulting in the loss of cognitive functions such as memory, reasoning, language, and cognitive, social, physical, and emotional control, to the extent that losses interfere with activities of daily living and necessitate continuous monitoring and care. Many studies now show that the processing machinery of the brain is plastic and remodeled throughout life by learning and experience, enabling the strengthening of cognitive skills or abilities. Research has shown that brief, daily computerized cognitive training that is sufficiently challenging, goal-directed and adaptive enables intact brain structures to restore balance in attention and compensate for disruptions in cognitive functioning. The study aims to understand how our computer program can affect cognition and attention in those with aging brain.

Official Title
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Plasticity-based Adaptive Cognitive Remediation for Alzheimer Disease

Conditions
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Older Adults, Aging Brain

Intervention / Treatment
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* Behavioral: Computerized Plasticity-based Software
* Behavioral: Commercially available Video Game


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 65-79 years at the time of consent Fluent English speakers, to ensure reasonable results neuropsychological assessments Adequate sensorimotor capacity to perform the program, including visual capacity adequate to read from a computer screen at a normal viewing distance, auditory capacity adequate to understand normal speech, and motor capacity adequate to control a computer mouse No evidence of dementia as indicated by Montreal Cognitive Assessment (MoCA) scores >25 Exclusion Criteria: Diagnosis with Alzheimer's disease or related dementias Requiring caregiver assistance in dressing/personal hygiene Medical conditions predisposing to imminent functional decline Recent participation of computer-delivered cognitive training Diagnosis of an illness or condition with known cognitive consequences (e.g., schizophrenia, bipolar disorder, cancer, multiple sclerosis) will be excluded due to the confound with cognitive impairment from normal aging. Uncorrectable acuity greater than 20/40 Self-reported cardiovascular disease Claustrophobia or any other contraindication to MRI scanning Inability to complete a 1-hour MRI Any implanted devices above the waist (e.g., cardiac pacemaker or auto-defibrillators, neural pacemaker, aneurysm clips, cochlear implant, metallic bodies in the eye or central nervous system, any form of wires or metal devices that may concentrate radio frequency fields) History of brain surgery; removal of brain tissue; or history of stroke.

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Computerized Plasticity-based Software<br>Computerized Plasticity-based software training requiring a total maximum of 50 treatment sessions, 4-5 times weekly, 40 minutes each session. | Behavioral: Computerized Plasticity-based Software<br>* Participants will be asked to use their assigned training program for forty minutes per session, up to five sessions per week, over 10 weeks (50 total sessions).<br>|
| Active Comparator: Commercially available video game<br>Commercially available video game training. Treatment is software based, will occur up to 50 times throughout study duration, 4-5 times per week, 40 minutes each session.. | Behavioral: Commercially available Video Game<br>* Participants will be asked to use their assigned video games for forty minutes per session, up to five sessions per week, over 10 weeks (50 total sessions).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in performance on global cognitive composite score | Change in performance on global cognitive composite score based on the average of all normalized assessment measures. | Baseline and at the completion of 10 weeks of training | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in brain function | Change in resting state functional connectivity will be measured by resting State T2*weighted EPI-BOLD, a 10-minute task-free BOLD contrast sequence consisting of 300 volumes (TR=2000 ms/TE=30ms) at 3.4mm3 in-plane resolution and 3mm slice thickness. Participants will be instructed to keep their eyes open and maintain attention on a central gray fixation cross on a black screen. | Baseline and at the completion of 10 weeks of training | 
| Changes in brain structure | 3D T1-Weighted multi-echo MPRAGE. Morphometric analyses will be based on this MRI sequence (not accelerated because the reliability of acceleration for multi-site studies has not yet been established). We will achieve spatial resolution of 1 x 1 x 1 mm voxels. | Baseline and at the completion of 10 weeks of training | 
| Changes in task-related brain activation | Change in functional connectivity and brain activation will be measured while performing Flanker Task. | Baseline and at the completion of 10 weeks of training | 
| Changes in performance on memory composite score | Change in performance on memory will be measured using the composite score created by averaging the z-scores of Visual Short Term Memory, Spatial Working Memory and N-Back tasks. | Baseline and at the completion of 10 weeks of training | 
| Changes in performance on executive function composite score | Change in performance on executive function will be measured using the composite score created by averaging the z-scores for the Flanker, Stroop and Trail Making tasks. | Baseline and at the completion of 10 weeks of training | 
| Changes in performance on processing speed composite score | Change in performance on processing speed will be measured using the composite score created by averaging the z-scores of Pattern Comparison, Letter Comparison, and Digit Symbol Coding tasks. | Baseline and at the completion of 10 weeks of training |