Aging, Cognitive Decline, Frailty, Muscle Degeneration, Physical Disability, Sarcopenia
Conditions
Keywords
Aging, Motor control, Cognitive function, Neuroplasticity, Brain health, Muscular fitness, Exerkines, Myokines, (Neuro)inflammation
Brief summary
BRAIN-M is a randomized controlled trial designed to examine the effects of a single bout or 12 weeks of blood-flow restriction training or high-intensity resistance training on cognitive function, brain health, muscular properties and physical performance in healthy older men 60-75 years old.
Detailed description
The BRAIN-M project is driven by the idea that understanding the mechanisms through which muscle and brain interact could offer new approaches to magnifying the beneficial and detrimental effects of exercise training on health at older age. Specifically, the investigators aim at identifying brain, blood, and muscle biomarkers that could serve as predictors of response to exercise training at either cognitive, brain, muscle or physical performance levels and study the associations between biomarkers in order to suggest a physiological model of brain-muscle and muscle-brain crosstalk in ageing. 60 male older adults (60-75y old) will be included in either 12 weeks of high-intense blood-flow restriction training (n = 20), muscle damaging resistance training (n = 20) or no exercise (n = 20). The control group will be asked to maintain their usual lifestyle.
Interventions
BEHAVIORALBFRT
Following a warm-up of 10 min, subjects in the experimental group will undergo BFRT for two times per week, consisting of lower extremity exercises (leg press, knee extension, knee flexion). BFRT will be at 40% of 1 repetition maximum (1RM); The volume % (V% = number of repetitions x number of sets x number of exercises x % 1 repetition max) = 57.6%. Progression during the 12 week program will be attained by a 1RM test every 4 weeks.
BEHAVIORALMDRT
Following a warm-up of 10 min, subjects in the experimental group will undergo MDRT for two times per week, consisting of lower extremity exercises (leg press, knee extension, knee flexion). The exercise will be at 80% of 1RM concentric-only or 120% of 1RM eccentric-only in a 3:1 ratio. The volume % (V% = number of repetitions x number of sets x number of exercises x % 1 repetition max) = 57.6%. Progression during the 12 week program will be attained by a 1RM test every 4 weeks.
Sponsors
Research Council of Lithuania
Lithuanian University of Health Sciences
Maastricht University
Vrije Universiteit Brussel
KU Leuven
Wingate Institute
Lithuanian Sports University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
60 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* healthy male older adults * able to speak and read fluent Lithuanian * living in community during the study
Exclusion criteria
* cognitive and neurological disorders (e.g. dementia, stroke, Parkinson, multiple sclerosis) * previous lower extremity injury * diabetes mellitus type I or II * no oncologic disease * no bone fractures in the previous year * deep vein thrombosis * cardiovascular disorders (e.g. congestive heart failure, angina pectoris, uncontrolled arrhythmia, history of myocardial infarction or coronary bypass grafting in the past year) * obesity (BMI \>30kg/m²) * chronic fatigue, chronic headache, or chronic dizziness * ineligibility to MRI scanning (e.g. due to claustrofobia or metal implants) * The participants should not be engaged in any regular exercise programme during the previous 6 months (according to IPAQ), but able to perform 10 sit-ups * Any other consideration that interferes with the study aims and/or risk to the participant, at the discretion of the researcher
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in cognitive function on the Switching task (executive function) | Before first exercise bout, immediately after first exercise bout, 1 hour after the first exercise bout and after the 12 week intervention period | The switching task is a complex task where subjects need to switch (executive function) between a manikin task (visuospatial skill, attention and problem solving) and a mathematical computation task (mathematical computation skill, concentration and working memory). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in lactate levels | Before first exercise bout, immediately after first exercise bout, 1 hour after the first exercise bout | Capillary lactate levels will be measured in the acute exercise test. |
| Changes in blood serum levels of TNFalpha and syndecan | Before first exercise bout, immediately after first exercise bout, 1 hour after the first exercise bout | We will use enzyme-linked immunosorbent assays (ELISAs) to measure acute changes in TNFalpha, and syndecan before and after the first exercise bout. |
| Changes in blood plasma levels of BDNF | Before first exercise bout, immediately after first exercise bout, 1 hour after the first exercise bout and after the 12 week intervention period | We will use enzyme-linked immunosorbent assays (ELISAs) to measure acute and chronic changes in BDNF before and after the first exercise bout; and after 12 weeks intervention |
| Changes in blood serum levels of IGF-1, IL-6 and kynurenine | Before and after the 12 week intervention period | We will use enzyme-linked immunosorbent assays (ELISAs) to measure chronic changes in IGF-1, IL-6 and kynurenine before and after 12 weeks intervention |
| Changes in blood CK levels | Before first exercise bout and every 3 weeks for a total of 7 times 48 hours after the eccentric-only training session in the MDRT group. | Blood CK levels will be measured in the MDRT group 48 hours after each eccentric-only training session to assess the muscle damaging effect/repeated bout effect. |
| Changes in muscle contractile characteristics (with tensiomyography (TMG)) | Before and after the 12 week intervention period | Muscle involuntary contractile characteristics of the lower-limb muscles-the rectus femoris (RF), vastus medialis (VM), vastus lateralis (VL), biceps femoris (BF), semitendinosus (ST), tibialis anterior (TA), gastrocnemius medialis (GM) and gastrocnemius lateralis (GL)-will be recorded by measuring the response of these muscles to an induced electric stimulus (provoked by two self-adhesive electrodes) using TMG equipment on both the left and right lower extremities. |
| Changes in BMI | Before and after the 12 week intervention period | Weight and height will be combined to report BMI in kg/m\^2 |
| Changes in body fat % | Before and after the 12 week intervention period | body fat % will be measured using bio-impedance analysis (Tanita) |
| Changes in SMI | Before and after the 12 week intervention period | Skeletal muscle mass index (SMI, kg/m\^2) will be measured using bio-impedance analysis (Tanita) |
| Changes in fat free mass | Before and after the 12 week intervention period | Fat free mass (kg) will be measured using bio-impedance analysis (Tanita) |
| Changes in patellar tendon crossectional area | Before and after the 12 week intervention period | Ultrasound will be used to assess the crossectional area (cm\^2) of the pattella tendon |
| Changes in patellar tendon stiffness | Before and after the 12 week intervention period | While producing isometric knee extension force, ultrasound will be used to assess patellar tendon distension, which is a measure of tendon stiffness. |
| Changes in quadriceps muscle fascicle length | Before and after the 12 week intervention period | Ultrasound will be used to quantify muscle geometrical properties such as fascicle length (cm). |
| Changes in quadriceps muscle fascicle angle | Before and after the 12 week intervention period | Ultrasound will be used to quantify muscle geometrical properties such as fascicle angle (°). |
| Changes in quadriceps muscle thickness | Before and after the 12 week intervention period | Ultrasound will be used to quantify muscle geometrical properties such as quadriceps muscle thickness. |
| Changes in quadriceps muscle cross-sectional area | Before and after the 12 week intervention period | MRI will be used to measure muscle cross-sectional volume changes of the quadriceps muscles |
| Change in cognitive function on the 2-Choice Reaction time (processing speed), Go/No-Go (inhibition) or 6 letter Memory Search (memory) test | Before first exercise bout, immediately after first exercise bout, 1 hour after the first exercise bout and after the 12 week intervention period | Cognitive functioning will be assessed with the Automated Neuropsychological Assessment Metrics 4 (ANAM4) cognitive test battery, testing several cognitive domains. |
| Changes in quadriceps muscle intramuscular fat | Before and after the 12 week intervention period | H-MRS (proton magnetic resonance spectroscopy) will be used to measure intramuscular fat in the quadriceps muscle |
| Changes in brain gray matter volume (with magnetic resonance imaging) | Before and after the 12 week intervention period | MRI will be used to measure changes in gray matter volume using T1 images |
| Changes in brain white matter volume (with magnetic resonance imaging) | Before and after the 12 week intervention period | MRI will be used to measure changes in white matter integrity using DTI sequence |
| Changes in brain neural integrity (with proton magnetic resonance spectroscopy) | Before and after the 12 week intervention period | H-MRS will be used to measure changes in N-acetylaspartate levels in specific brain regions: right dorsolateral prefrontal cortex, left hippocampus and left primary sensorimotor cortex. |
| Changes in brain neuroinflammation (with proton magnetic resonance spectroscopy) | Before and after the 12 week intervention period | H-MRS will be used to measure changes in myo-inositol levels in specific brain regions: right dorsolateral prefrontal cortex, left hippocampus and left primary sensorimotor cortex. |
| Changes in brain neuroplasticity marker (with proton magnetic resonance spectroscopy) | Before and after the 12 week intervention period | H-MRS will be used to measure changes in Glx in specific brain regions: right dorsolateral prefrontal cortex, left hippocampus and left primary sensorimotor cortex. |
| Changes in balance (with posturography on Kistler platform) | Before and after the 12 week intervention period | Balance will be assessed in four different positions (two legs stance vs Romberg stance with eyes open vs closed) with or without a cognitive task to measure dual task effects. |
| Changes in handgrip strength | Before and after the 12 week intervention period | Handgrip strength will be measured using Jamar dynamometry |
| Changes in maximal isometric strength (with Biodex) | Before and after the 12 week intervention period | Knee extension/flexion maximal isometric strength (N) will be measured using Biodex. |
| Changes in isokinetic peak torque (with Biodex) | Before and after the 12 week intervention period | Knee extension/flexion isokinetic peak torque measurements will be done at 60°/s |
| Changes in rate of force development (with Biodex) | Before and after the 12 week intervention period | Rate of force development will be measured during maximal knee extension/flexion movement. |
| Changes in physical performance (with the Fitness Fullerton Test battery for the Senior) | Before and after the 12 week intervention period | Determination of motor control tasks relevant to daily life activities. A selection of tests, including the sit-to-stance test, timed up-and-go test, and other physical tests |
| Changes in subjective quality of life (patient reported outcome questionnaires) | Before and after the 12 week intervention period | Quality of life will be assessed using the World Health Organisation 100 (WHO 100) questionnaire |
| Changes in nutrition (patient reported outcome questionnaires) | Before and after the 12 week intervention period | We will use a selection of patient reported outcome measures to evaluate their nutrition (using the Actual nutrition registration questionnaire). |
| Changes in subjective sleep quality (patient reported outcome questionnaires) | Before and after the 12 week intervention period | We will use a selection of patient reported outcome measures to evaluate their quality of sleep (using the Stanford sleep quality scale). |
| Changes in reported physical activity levels (patient reported outcome questionnaires) | Before and after the 12 week intervention period | We will assess physical activity levels using the International Physical Activities Questionnaire (IPAQ) |
| Changes in quadriceps muscle fiber type | Before and after the 12 week intervention period | H-MRS (proton magnetic resonance spectroscopy) will be used to measure fiber type in the quadriceps muscle |
Countries
Lithuania
Outcome results
None listed