Brain Enhancement Training Towards Elders Resilience to Aging, Phase IIB

Study Overview
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Brief Summary
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This study aims to examine the longer-term benefits of a novel, neuroplasticity-based, computerized and web-deliverable training program (PACR-CT) five years from the initial 10 weeks of training from our Phase II study - Protocol #: PSC-0605-17 (Aim 1) and test the interactive effect of previous training and 10 weeks of booster training (Aim 2). Both the study and the software being investigated meet the criteria of Non-Significant Risk.

Detailed Description
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This study will employ a single arm, open label design with use of the PACR-CT with all participants who completed the Phase II study, as well as approximately 60 new participants (with a goal of 40 completers) who are age-matched and untrained older adults. After consent, only the new, untrained participants will complete the screening visit. Then all participants will perform the pre-training visit (cognitive and functional assessments, MRI/fMRI and blood draw), followed by 10 weeks of training, and then followed by post-training visit (cognitive and functional assessments and MRI/fMRI).

Official Title
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BETTER Aging Trial: Brain Enhancement Training Towards Elders Resilience to Aging, Phase IIB

Conditions
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Age-related Cognitive Decline

Intervention / Treatment
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* Other: Computerized Plasticity-Based Adaptive Cognitive Training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be 70 years of age or older Participant must be a fluent English speaker Participant must have 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 Participant must not have evidence of dementia as indicated by the Montreal Cognitive Assessment (MoCA) Exclusion Criteria: Participant with any medical illnesses, injuries or conditions predisposing to imminent functional and/or cognitive decline Participant requiring caregiver assistance in dressing/personal hygiene Participant with severe visual deficits (including visual neglect, partial field cuts, anopias) and/or severe hearing deficit that would prevent use of the computerized treatment program Participant with recent participation of computer-delivered cognitive training within 2 years of consent Participant with claustrophobia or any other contraindication to MRI scanning Participant with inability to complete a 1-hour MRI Pregnant women Participant with 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) Participants with active suicidal ideation with specific plan and intent or suicide-related behaviors within 2 months of consent as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)

Ages Eligible for Study
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Minimum Age: 70 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Treatment<br>Computerized plasticity-based adaptive cognitive training requiring a total maximum of 50 treatment sessions, up to 5 sessions per week, 42 minutes per session. | Other: Computerized Plasticity-Based Adaptive Cognitive Training<br>* Forty-two minutes of training on computerized exercises that targets processing speed, memory and attention.<br>* Other names: PACR-CT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in performance on global cognitive composite score | Change in performance on global cognitive composite score based on the average of all normalized assessment measures. | At 5 years and at 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change 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. | At 5 years and at 3 months | 
| Change in performance on working memory | Change in performance on working memory will be measured using the composite score created by averaging the z-scores of Visual Short Term Memory and N-Back Tasks. | At 5 years and at 3 months | 
| Changes in performance on episodic memory | Change in performance on episodic memory will be measured using the composite score created by averaging the z-scores of Selective Reminding Task and Face Name Task. | At 5 years and at 3 months | 
| Change in performance on executive function | Change in performance on executive function will be measured using the composite score created by averaging the z-scores of Flanker Task and Task Switch (fMRI task). | At 5 years and at 3 months | 
| Change 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. | At 5 years and at 3 months | 
| Change 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. | At 5 years and at 3 months | 
| Change in task-related brain activation | Change in functional connectivity and brain activation will be measured while performing Task Switch. | At 5 years and at 3 months | 
| Change in functional performance | Between-group magnitude of change in sum time of all tasks in the Timed Instrumental Activities of Daily Living (TIADL). Higher scores indicate greater impairment in functional performance. | At 5 years and at 3 months | 
| Change in Depressive Symptoms | Between-group magnitude of change in sum score using the self-report measure, Center for Epidemiologic Studies Depression Scale (CES-D). The scoring range is 0-60. Higher scores indicate the presence of more symptomatology. | At 5 years and at 3 months | 
| Blood-based Biomarker for Alzheimer's Disease | Group differences in the P-tau181, Aβ1-42/Aβ1-40 concentrations | At 5 years |