Active Gains in Brain Using Exercise During Aging

Study Overview
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Brief Summary
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AGUEDA (Active Gains in brain using Exercise During Aging) is a randomized controlled trial designed to examine the effects of a 24-week resistance exercise program on brain health in cognitively normal adults between 65-80 years of age.

Detailed Description
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Exercise has emerged as the most promising non-pharmacologic intervention for improving brain health in older adults. The main aim of AGUEDA (Active Gains in brain using Exercise During Aging) trial is to examine the effects of a 6-month resistance exercise program on executive function in cognitively normal older adults. The secondary aims are (i) to examine the effects of exercise on central and peripheral brain markers, and (ii) to investigate mediators and moderators of the exercise-derived improvements observed in executive function and brain markers. AGUEDA is a randomized controlled trial in which 90 cognitively normal older adults, aged 65-80 years old, will be randomized into an exercise group (n=45) or a wait-list control group (n=45). Participants assigned to the exercise group will participate in a 24-week resistance exercise program (3 sessions/week, 60 min/session), while the control group will be asked to maintain their usual lifestyle. A comprehensive neuropsychological test battery, amyloid PET scan, cutting-edge MRI scan, DXA scan, physical ﬁtness, physical function and physical activity measures will be used. Blood, saliva and fecal samples will be collected. Mental health and psychosocial variables will be self-reported.

Official Title
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Active Gains in Brain Using Exercise During Aging: AGUEDA Trial

Conditions
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Healthy, Cognitive Function 1, Social

Intervention / Treatment
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* Behavioral: 24-week resistance exercise program


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women 65 - 80 years. Able to speak and read fluent Spanish. Living in community during the study. Reliable means of transportation. Being physical inactive (i.e., not to be participating in the last 6 months in any resistance exercise program, or accumulating less than 600 METS/Week of moderate-vigorous physical activity). Classified as cognitively normal according to Stics-m MMSE and MOCA tests. Exclusion Criteria: Ambulatory with pain or regular use of an assisted walking device. Medical contraindication for inclusion in an exercise program. Neurological condition (Multiple Sclerosis, Parkinson Disease, Dementia) or brain injury (traumatic or stroke). Current diagnosis and treatment of a DSM-V Axis I or II disorder including major depression and seeing a psychologist, therapist, or psychiatrist. History of major psychiatric illness including schizophrenia, general anxiety disorder or depression (GDS-30>=15). Current treatment for congestive heart failure, angina, uncontrolled arrhythmia, deep venous thrombosis or other cardiovascular event. Myocardial infarction, coronary artery bypass grafting, angioplasty or other cardiac condition in the past year. Current or previous treatment for any type of cancer. Type I Diabetes or uncontrolled Type II Diabetes defined as Insulin dependent or Hba1C greater than 10. Recent treatment for alcohol or substance abuse. Presence of metal implants (e.g., pacemaker, stents, joint replacement) that would be MRI ineligible. Claustrophobia. Color blindness. Diagnosis of COVID-19 with hospitalization in intensive care unit. Any other consideration that interferes with the study aims and could be a risk to the participant, at the discretion of the researcher.

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 80 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 24-week resistance exercise program<br>Participants will engage in supervised 24-week resistance exercise program with goal of maintaining 180 minutes of exercise per week. | Behavioral: 24-week resistance exercise program<br>* This group will perform a 24-week resistance exercise program. Participants will engage in 180 minutes/week of resistance exercise (3 supervised sessions peer week, 60 min/session). The training will consist of a combination of upper and lower body exercises using elastic bands and participants' body weight as the primary resistance. Exercise load and intensity will be based on the number of repetitions (i.e.,10-12 repetitions), resistance of the elastic bands, in ascending order with seven intensities, and also on the exercises' difficulty (i.e., three levels). The prescribed targeted intensity will reach 70-80% of the participants' maximum rating perceived exertion (i.e., 7-8 RPE).The progression (horizontal) will be standardized according to the execution time and RPE, and individualized according to execution speed and band resistance. Heart rate will be monitored in all sessions. Further, intrinsic motivation before and after session and sleep quality will be registered.<br>|
| No Intervention: Wait-list control group<br>Control group will be asked to maintain their usual lifestyle. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in executive function | The main outcome is change in executive function from baseline to 6 months. The 3-month measure is used to assess the trajectory of the change. A comprehensive neuropsychological battery will assess several domains of executive function: working memory, cognitive flexibility and inhibitory control. | Baseline, 3 months and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in brain amyloid beta | PET (positron emission tomography) scan using the tracer Neuraceq (Florbetaben F18) will measure levels of the protein amyloid beta in the brain. | Baseline and 6 months | 
| Change in brain morphology | MRI (magnetic resonance imaging) will measure brain morphology including volume, area, cortical thickness and shapes by a T1-weighted MPRAGE structural sequence. | Baseline and 6 months | 
| Change in hippocampal brain morphology | MRI (magnetic resonance imaging) will measure hippocampal morphology including volume, area, cortical thickness, shapes by a high resolution hippocampus sequence. | Baseline and 6 months | 
| Change in white matter structure | MRI (magnetic resonance imaging) will measure white matter structure and lesions by diffusion weighted acquisition sequence. | Baseline and 6 months | 
| Change in brain function | MRI (magnetic resonance imaging) will measure brain function including both resting state and n-back working memory task-evoked patterns. Measures of brain activity and brain connectivity will be calculated. | Baseline and 6 months | 
| Change in cerebral blood flow | MRI (magnetic resonance imaging) will measure cerebral blood flow by Pseudo-Continuous Arterial Spin Labeling (pCASL) sequence. | Baseline and 6 months | 
| Change in peripheral amyloid beta | Saliva and blood samples will be used to determine peripheral amyloid beta | Baseline and 6 months | 
| Change in other peripheral neurology biomarkers | Saliva and blood samples will be used to determine peripheral neurology biomarkers including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and cathepsin B (CTSB). | Baseline and 6 months | 
| Change in memory performance | Visuospatial memory will be assessed by the Rey-Osterreith figure (ROF) test, verbal memory by the Rey Auditory Verbal Learning Test (RAVLT) and confrontational word memory by the boston Naming Test (short version, BNT). | Baseline and 6 months | 
| Change in fluid and crystallized intelligence | Intelligence will be assessed by the Wechsler Adult Intelligence Scale (WAIS-IV). 3 subtests for crystallized intelligence (Similarities, Vocabulary, information) and 3 subtests for fluid intelligence (Block Design, Matrix Reasoning, Visual Puzzles). | Baseline and 6 months | 
| Change in general cognition | General cognition will be assessed by the Telephone Interview for Cognitive Status (STICS-m), the Mini mental state examination (MMSE) and the Montreal Cognitive Assessment (MOCA. vocabulary/language and subjective and objective cognitive decline will be assessed by paper-based tests. | Baseline and 6 months | 
| Change in other cognitive outcomes | Vocabulary/language, and subjective and objective cognitive decline will be assessed by paper-based tests. | Baseline and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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brain, cognition, executive function, exercise, brain-gut axis, positron emission tomography, magnetic resonance imaging, aging, preclinical Alzheimer Disease stages