Active Gains in Brain Using Exercise During Aging

Healthy Clinical Trial

— AGUEDA  

Official title:

Active Gains in Brain Using Exercise During Aging: AGUEDA Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05186090
• Other study ID #: RTI2018-095284-J-I00
• Status: Completed
• Phase: N/A
• Start date: January 2, 2021
• Est. completion date: December 11, 2022

Study information

• Verified date: March 2024
• Source: Universidad de Granada
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: December 11, 2022
• Est. primary completion date: December 11, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cognitive Function 1, Social
• Healthy

Intervention

Behavioral:
• 24-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.

Locations

Country	Name	City	State
Spain	University of Granada	Granada	Andalucia

Sponsors (5)

Lead Sponsor	Collaborator
Universidad de Granada	Centro de Investigación Mente, Cerebro y Comportamiento (CIMCYC), Instituto Mixto Universitario Deporte y Salud (iMUDS), University Hospital Virgen de las Nieves, University of Pittsburgh

Country where clinical trial is conducted

Spain, 

References & Publications (4)

Fernandez-Gamez B, Solis-Urra P, Olvera-Rojas M, Molina-Hidalgo C, Fernandez-Ortega J, Lara CP, Coca-Pulido A, Bellon D, Sclafani A, Mora-Gonzalez J, Toval A, Martin-Fuentes I, Bakker EA, Lozano RM, Navarrete S, Jimenez-Pavon D, Liu-Ambrose T, Erickson KI, Ortega FB, Esteban-Cornejo I. Resistance Exercise Program in Cognitively Normal Older Adults: CERT-Based Exercise Protocol of the AGUEDA Randomized Controlled Trial. J Nutr Health Aging. 2023;27(10):885-893. doi: 10.1007/s12603-023-1982-1. — View Citation

Rodriguez-Ayllon M, Solis-Urra P, Arroyo-Avila C, Alvarez-Ortega M, Molina-Garcia P, Molina-Hidalgo C, Gomez-Rio M, Brown B, Erickson KI, Esteban-Cornejo I. Physical activity and amyloid beta in middle-aged and older adults: A systematic review and meta-analysis. J Sport Health Sci. 2023 Aug 7:S2095-2546(23)00074-1. doi: 10.1016/j.jshs.2023.08.001. Online ahead of print. — View Citation

Solis-Urra P, Molina-Hidalgo C, Garcia-Rivero Y, Costa-Rodriguez C, Mora-Gonzalez J, Fernandez-Gamez B, Olvera-Rojas M, Coca-Pulido A, Toval A, Bellon D, Sclafani A, Martin-Fuentes I, Trivino-Ibanez EM, de Teresa C, Huang H, Grove G, Hillman CH, Kramer AF, Catena A, Ortega FB, Gomez-Rio M, Erickson KI, Esteban-Cornejo I. Active Gains in brain Using Exercise During Aging (AGUEDA): protocol for a randomized controlled trial. Front Hum Neurosci. 2023 May 22;17:1168549. doi: 10.3389/fnhum.2023.1168549. eCollection 2023. — View Citation

Solis-Urra P, Rodriguez-Ayllon M, Alvarez-Ortega M, Molina-Hidalgo C, Molina-Garcia P, Arroyo-Avila C, Garcia-Hermoso A, Collins AM, Jain S, Gispert JD, Liu-Ambrose T, Ortega FB, Erickson KI, Esteban-Cornejo I. Physical Performance and Amyloid-beta in Humans: A Systematic Review and Meta-Analysis of Observational Studies. J Alzheimers Dis. 2023;96(4):1427-1439. doi: 10.3233/JAD-230586. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in muscular strength	Muscular strength will be assessed by laboratory (i.e. isokinetic test) and field- based (i.e., handgrip and functional tests) tests	Baseline, 3 months (only for field-based tests) and 6 months
Other	Change in physical function	Senior Fitness Test and Short Physical Performance Battery will assess overall physical functioning and z-scores will be calculated.	Baseline, 3 months and 6 months
Other	Change in gait speed and variability	Gait analysis will be assessed by the OptoGait System	Baseline and 6 months
Other	Change in cardiorespiratory fitness	Cardiorespiratory fitness will be assessed by 2 field-based tests ( i.e., 6-min walking test and 2-km walking test)	Baseline and 6 months
Other	Change in mental health outcomes, specifically psychological ill-being	A battery of questionnaire will assess psychological ill-being (i.e. depression, anxiety, stress or negative affect).	Baseline and 6 months
Other	Change in mental health outcomes, specifically psychological well-being.	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).	Baseline and 6 months
Other	Change in quality of life	This will be self-reported using the Health Survey Short Form (SF-36).	Baseline and 6 months
Other	Change in 24-hours movement behaviors	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	Baseline and 3 months
Other	Change in sedentary behaviors	Type of sedentary behaviors will be self-reported by questionnaire.	Baseline and 6 months
Other	Change in diet behaviors	This will be self-reported using the food-frequency questionnaire (FFQ) and the PREDIMED-14 questionnaire.	Baseline and 6 months
Other	Change in body composition	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.	Baseline and 6 months
Other	Change in neck adipose tissue	Neck adipose tissue will be assessed by MRI	Baseline and 6 months
Other	Change in blood pressure	Systolic and diastolic blood pressure will be assessed by a blood pressure monitor	Baseline and 6 months
Other	Change in peripheral inflammatory and cardiovascular biomarkers	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	Baseline and 6 months
Other	Change in epigenetics and gene expression	Blood samples will be stored for genetic analyses, including APOE and BDNF genotypes	Baseline and 6 months
Other	Change in oral and gut microbiota	Saliva and fecal samples will be used to determine oral and gut microbiota including the most representative phyla (i.e., firmicutes, bacteroidetes, and proteobacteria.	Baseline and 6 months
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in peripheral amyloid beta	Saliva and blood samples will be used to determine peripheral amyloid beta	Baseline and 6 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in other cognitive outcomes	Vocabulary/language, and subjective and objective cognitive decline will be assessed by paper-based tests.	Baseline and 6 months

External Links

•   AGUEDA website