Cognitive Function 1, Social, Healthy
Conditions
Keywords
brain, cognition, executive function, exercise, brain-gut axis, positron emission tomography, magnetic resonance imaging, aging, preclinical Alzheimer Disease stages
Brief summary
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
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.
Interventions
BEHAVIORAL24-week resistance exercise program
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.
Sponsors
Instituto Mixto Universitario Deporte y Salud (iMUDS)
Centro de Investigación Mente, Cerebro y Comportamiento (CIMCYC)
University Hospital Virgen de las Nieves
University of Pittsburgh
Universidad de Granada
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to 80 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in executive function | Baseline, 3 months and 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in brain morphology | Baseline and 6 months | MRI (magnetic resonance imaging) will measure brain morphology including volume, area, cortical thickness and shapes by a T1-weighted MPRAGE structural sequence. |
| Change in hippocampal brain morphology | Baseline and 6 months | MRI (magnetic resonance imaging) will measure hippocampal morphology including volume, area, cortical thickness, shapes by a high resolution hippocampus sequence. |
| Change in white matter structure | Baseline and 6 months | MRI (magnetic resonance imaging) will measure white matter structure and lesions by diffusion weighted acquisition sequence. |
| Change in brain function | Baseline and 6 months | 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. |
| Change in cerebral blood flow | Baseline and 6 months | MRI (magnetic resonance imaging) will measure cerebral blood flow by Pseudo-Continuous Arterial Spin Labeling (pCASL) sequence. |
| Change in brain amyloid beta | Baseline and 6 months | PET (positron emission tomography) scan using the tracer Neuraceq (Florbetaben F18) will measure levels of the protein amyloid beta in the brain. |
| Change in other peripheral neurology biomarkers | Baseline and 6 months | 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). |
| Change in memory performance | Baseline and 6 months | 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). |
| Change in fluid and crystallized intelligence | Baseline and 6 months | 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). |
| Change in general cognition | Baseline and 6 months | 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. |
| Change in other cognitive outcomes | Baseline and 6 months | Vocabulary/language, and subjective and objective cognitive decline will be assessed by paper-based tests. |
| Change in peripheral amyloid beta | Baseline and 6 months | Saliva and blood samples will be used to determine peripheral amyloid beta |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in peripheral inflammatory and cardiovascular biomarkers | Baseline and 6 months | Saliva and blood samples will be used to determine peripheral biomarkers including tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), glucose, insulin, HDL and LDL cholesterol |
| Changes in muscular strength | Baseline, 3 months (only for field-based tests) and 6 months | Muscular strength will be assessed by laboratory (i.e. isokinetic test) and field- based (i.e., handgrip and functional tests) tests |
| Change in oral and gut microbiota | Baseline and 6 months | Saliva and fecal samples will be used to determine oral and gut microbiota including the most representative phyla (i.e., firmicutes, bacteroidetes, and proteobacteria. |
| Change in epigenetics and gene expression | Baseline and 6 months | Blood samples will be stored for genetic analyses, including APOE and BDNF genotypes |
| Change in physical function | Baseline, 3 months and 6 months | Senior Fitness Test and Short Physical Performance Battery will assess overall physical functioning and z-scores will be calculated. |
| Change in gait speed and variability | Baseline and 6 months | Gait analysis will be assessed by the OptoGait System |
| Change in cardiorespiratory fitness | Baseline and 6 months | Cardiorespiratory fitness will be assessed by 2 field-based tests ( i.e., 6-min walking test and 2-km walking test) |
| Change in mental health outcomes, specifically psychological ill-being | Baseline and 6 months | A battery of questionnaire will assess psychological ill-being (i.e. depression, anxiety, stress or negative affect). |
| Change in mental health outcomes, specifically psychological well-being. | Baseline and 6 months | A battery of questionnaire will assess psychological well-being (i.e. self-esteem, self-concept, self-efficacy, self-image, positive affect, optimism, happiness and satisfaction with life). |
| Change in quality of life | Baseline and 6 months | This will be self-reported using the Health Survey Short Form (SF-36). |
| Change in 24-hours movement behaviors | Baseline and 3 months | Physical activity at different intensities (average min/day), sedentary time (average min/day) and sleep (average min/day) will be measured using Actigraph GT3X + accelerometers |
| Change in sedentary behaviors | Baseline and 6 months | Type of sedentary behaviors will be self-reported by questionnaire. |
| Change in diet behaviors | Baseline and 6 months | This will be self-reported using the food-frequency questionnaire (FFQ) and the PREDIMED-14 questionnaire. |
| Change in body composition | Baseline and 6 months | Body composition \[i.e., lean mass (kg), fat mass (kg), and bone mineral content and density (z-score)\] will be assessed using a dual-energy x-ray absorptiometer (DXA). Full- body, bilateral hips and lumbar spine scans will be acquired. |
| Change in neck adipose tissue | Baseline and 6 months | Neck adipose tissue will be assessed by MRI |
| Change in blood pressure | Baseline and 6 months | Systolic and diastolic blood pressure will be assessed by a blood pressure monitor |
Countries
Spain
Outcome results
None listed