The Impact of 6-months of Resistance Training on Intrinsic Capacity, Cognition, and Brain/Circulating Biomarkers of Neuroplasticity and Neuroinflammation in Older Adults With Mild Cognitive Impairment: a Randomized Controlled Trial.
Overview
- Phase
- N/A
- Intervention
- Not specified
- Conditions
- Mild Cognitive Impairment
- Sponsor
- Lithuanian Sports University
- Enrollment
- 80
- Locations
- 2
- Primary Endpoint
- Changes in intrinsic capacity
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
The goal of this clinical trial is to learn about the effect of long resistance training intervention on brain and muscle health in older adults with mild cognitive impairment (MCI). The main question it aims to answer is whether progressive resistance training can prevent/delay neurodegenerative/pro-inflammatory processes that are detrimental to cognition, mobility, vitality, and mental health of older adults with MCI. Participants will undergo 6 months of supervise resistance training. Subjects in the intervention group will undergo sessions of structural and functional magnetic resonance imaging, proton magnetic resonance spectroscopy at baseline and end of intervention. Blood analyses and functional and cognitive tests will be performed at baseline after 3 months from the start of intervention and at the end of the intervention. Observations obtained from the intervention group will compare to data collected from age-matched active control group who will undergo flexibility training of lower limb muscles.
Detailed Description
Physical exercise appears to be effective in preventing transitions from normal cognitive aging to mild cognitive impairments (MCI) and from MCI to dementia-related disorders such as Alzheimer's disease (AD). The investigators will examine the longitudinal effects of progressive resistance training on biomarkers of (neuro)inflammation and neuroplasticity in a cohort of community-dwelling older individuals at high risk of developing MCI. The investigators will focus specifically on the effects of 24 weeks of resistance training on structural and neurochemical properties of the hippocampus and associations between exercise-induced changes in those properties and improvement in functional ability as quantified by pre-to-post changes in the mobility, cognition, psychological and vitality composites of intrinsic capacity (IC). Similarly, the investigators will examine the association between exercise-induced changes in global internal capacity index and exercise-induced changes in the expressions of inflammatory biomarkers (specifically, IL-1β, IL-6, IL-10, IL-18, kynurenine, and TNFa), myokines (specifically, BDNF, IGF-1, irisin), and circulating biomarkers of neurodegeneration (specifically, neurofilament light chain - NfL), tauopathy (specifically, total and phosphorylated tau181) and amyloid pathology (specifically, Aβ42/Aβ40 ratio). Blood samples will be collected between 8 a.m. and 11 a.m. after fasting. Behavioral outcome measures from gait/balance tests, handgrip strength test, cognitive tests, psychological tests, etc. and serum/plasma levels of the circulating biomarkers will be assessed at baseline, mid-intervention time (12 weeks), immediately post-intervention time (24 weeks), and at six-month follow-up (48 weeks). Structural MRI (sMRI) images, diffusion MRI (dMRI) images, resting state functional MRI (rs-fMRI) data and proton magnetic resonance spectroscopy (1H-MRS) data from the brain and T1-wighted images and 1H-MRS spectra from the lower-limb musculature will be collected at baseline and immediately post-treatment time (24 weeks) using a Siemens 3T Skyra scanner. Findings from this study will be used to provide evidence-based frameworks for implementation of longitudinal exercise interventions in prevention of dementia-related neurodegenerative disease among older with MCI. Further, the investigators will assess the effects of exercise on longitudinal changes in muscle mass, muscle strength, and neuromuscular functioning and examine the associations between these changes and exercise induced changes in locomotion capacity and postural stability as well as the prevention of sarcopenia and frailty. Secondary (exploratory) outcome measures will be (1) effects of the longitudinal strength training program on brain structural and neurochemical properties and (2) demographic factors, physiological properties and/or biomarkers that predict response to the intervention.
Investigators
Vilma Dudoniene
Prof. Dr.
Lithuanian Sports University
Eligibility Criteria
Inclusion Criteria
- •Male and female 65+ years old,
- •Community-dwelling,
- •Sedentary (not engaged in any structured activity for exercise) or non-sedentary individuals who engaged in mild recreational activities for less than 150 min/week.
- •A score of 18 to 25 on the Montreal Cognitive Assessment (MoCA) with or without a diagnosis of MCI. The diagnosis of MCI will be confirmed by a qualified mental health care specialist at the screening evaluation according to the International Classification of Diseases (ICD-10) and the Petersen criteria (Petersen et al, 2014).
- •Fluent in Lithuanian.
Exclusion Criteria
- •Age \< 65 years.
- •MoCA ≥ 26 or MoCA \< 18,
- •Symptomatic heart or cardiopulmonary disorders, diabetes, diagnosis of renal/hepatic disease, oncology, brain injury, diagnosis of neurologic, psychiatric, or musculoskeletal diseases.
- •Physical or orthopedic conditions (rheumatic symptoms, chronic pain, fractures, acute muscle injuries) that limit the subject's ability to participate in the training program.
- •Moderate to severe intake of alcohol (intake of 3 drinks or more/day for men and 2 drink or more/day for women).
- •Current smoker
- •Intake of drugs or psychiatric medications.
- •Contraindications to perform MRI (e.g., claustrophobia, cardiac pacemaker, internal pacing wires, metal implants, etc.).
- •Body mass index (BMI) \> 35 kg/m2 or body weight \> 130 kg.
- •Participation in routine exercise or physical activities (IPAQ).
Outcomes
Primary Outcomes
Changes in intrinsic capacity
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Assessment of intrinsic capacity subdomains will be conducted according to the WHO ICOPE guidelines. Outcome measures: Locomotion capacity \[scale 0 to 12\] with higher scores indicating a better outcome. Cognition capacity \[scale: 0 to 4\], with higher scores indicating a better outcome. Psychological capacity (mood) \[scale: 0 to 4\] with higher scores indicating a better outcome. Vitality \[scale 0 to 12\], with higher scores indicating a better outcome. Sensory capacity index \[scale 0 to 3\], with higher scores indicating a better outcome. Capacity indexes for each of the above mentioned subdomains will be calculated as the scores obtained divided by the maximum possible scores \[scale 0 to 1\]. The global intrinsic capacity index will be calculated as the sum of the subdomain's capacity indexes \[scale 0 to 5\] with higher scores indicating a better outcome.
Changes in sway velocity
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Center of pressure (CoP) data will be collected in stance position with a single piezoelectric force plate (KISTLER, model 9286) under single and dual-task condition. Outcome measures: CoP sway velocity (CoPv) in ML and AP sway directions (millimiter/seconds). Lower sway velocity represents a better outcome.
Changes in circulating levels of c-terminal agrin fragment-22 (CAF22)
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Serum levels of c-terminal agrin fragment-22 \[picograms/milliliter (pg/ml)\] will be assessed using enzyme-linked immunosorbent assay (ELISA). Blood samples will be collected at the antecubital vein after 12-h fasting by a qualified medical professional. Serum samples will be stored in the refrigerator compartment of the laboratory of the Lithuanian Sports University at -80 degrees Celsius until further analysis.
Changes in brain cortical thickness
Time Frame: Baseline and Post-intervention time (24 weeks); Optional: follow-up at 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Whole brain T1-weighted images. Outcome measures: GM cortical thicknesses (in mm) of cortical substructures. Image processing: FreeSurfer software, version 6 (freely available).
Changes in brain WM microstructural organization
Time Frame: Baseline and Post-intervention time (24 weeks); Optional: follow-up at 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Participants will undergo whole brain diffusion-weighted imaging (DWI). Outcome measures will be the Fractional anisotropy (FA) of WM tracts in the brain. Image processing will be possible with the use of the ExploreDTI software (freely available).
Changes in performance on the Trail Making Test (TMT)
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Complete parts A and part B of the Trail Making Test Outcome measures: Time (in seconds) required to complete part A (Trail A scores) Time (in seconds) required to complete part B (Trail B scores) Shorter time indicated a better outcome.
Changes in agility
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
8-Foot timed up and go (8-foot TUG): Outcome measure: time to complete the task in seconds. Shorter time to complete the task represents a better outcome.
Changes in levels of Albumin (Alb)
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Albumin levels \[grams/deciliter (g/dL)\] will be measured with GBC-system XN-1500 blood analyzer. Blood samples will be collected at the antecubital vein after 12-h fasting by a qualified medical professional.
Changes in circulating levels of Kynurenine
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Serum levels of Kynurenine \[nanograms/milliliter(ng/ml)\] will be assessed with enzyme-linked immunosorbent assay (ELISA). Blood samples will be collected at the antecubital vein after 12-h fasting by a qualified medical professional. Serum samples will be stored in the refrigerator compartment of the laboratory of the Lithuanian Sports University at -80 degrees Celsius until further analysis.
Changes in brain volume properties
Time Frame: Baseline and Post-intervention time (24 weeks); Optional: follow-up at 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Whole brain T1-weighted images, T2-wighted images, T2\* relaxation images and fluid attenuated inversion recovery (FLAIR) images will be obtained. Outcome measures will be grey matter (GM) volumes, white matter (WM) volumes (WM) and WM hyperintensity (WMH) volumes \[all in cubic millimeter (mm\^3)\] of cortical and subcortical structures. A total WMH volume will be obtained by summing the volumes of hyperintensities from all of the substructures. A large WMH volume will be taken as an indicator for cerebrovascular abnormalities. Image processing: FreeSurfaer software, version 6 (freely available).
Changes in muscle contraction displacement
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Tensiomyography (TMG) of left and right rectus femoris (RF) and biceps femoris (BF) heads. Outcome measures: Muscle contraction displacement (Dm) of left/right RF and BF (in millimeter).
Changes in reaction time
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
ANAM4 cognitive test battery, including: Go/No-Go test (GNG), 6 Letter Memory Search test (6LMST), Manikin test (MNKT) Outcome measures: Reaction Time (in milliseconds) with shorter time indicating a better outcome.
Changes in Stroop interference score
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Stroop Color and Word test (SCWT) Outcome measure: interference score (in seconds) Interference = CWT - \[(WT + CT)/2\] where WT, CT, and CWT are times (in seconds) to complete the Word, Color, and Color-Word conditions, respectively. Lower interference score indicates a better outcome.
Changes in dual-task cost for sway velocity
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Dual task cost (DTC) will be quantified as % change of sway velocity from dual to single task relative to their single task values. Increased negative value represents a better outcome whereas increased positive value represents a worse outcome.
Changes in reaction accuracy
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
ANAM4 cognitive test battery, including: Go/No-Go test (GNG), 6 Letter Memory Search test (6LMST), Manikin test (MNKT) Outcome measures: % number of correct responses with higher value indicating a better outcome.
Changes in cognitive efficiency
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
ANAM4 cognitive test battery, including: Go/No-Go test (GNG), 6 Letter Memory Search test (6LMST), Manikin test (MNKT) Outcome measures: throughput (= number of correct responses divided by mean RT for correct responses) with higher value indicating a better outcome
Changes in levels of Hemoglobin (Hb)
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Hemoglobin levels \[grams/deciliter (g/dL)\] will be measured with GBC-system XN-1500 blood analyzer. Blood samples will be collected at the antecubital vein after 12-h fasting by a qualified medical professional.
Changes in circulating levels of brain-derived neurotrophic factor (BDNF)
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Plasma levels of BDNF \[picograms/milliliter(pg/mL)\] will be assessed with enzyme-linked immunosorbent assay (ELISA). Blood samples will be collected at the antecubital vein after 12-h fasting by a qualified medical professional. Plasma samples will be stored in the refrigerator compartment of the laboratory of the Lithuanian Sports University at -80 degrees Celsius until further analysis.
Changes in global cognition
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Outcome measure: scores on the Montreal cognitive assessment (MoCA) \[range 0 - 30\] with higher scores indicating better performance.
Changes in psychological assessment of depression
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Outcome measure: scores on the Geriatric depression scale (GDS), \[range 0-15\] with higher score indicate severe depression.
Changes in levels of C-reactive protein (CRP)
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
CRP levels \[milligrams/deciliter (mg/dL)\] will be measured with COBAS PRO blood analyzer. Blood samples will be collected at the antecubital vein after 12-h fasting by a qualified medical professional.
Changes in circulating levels of cytokines
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Serum levels of the interleukins IL-1β, IL-6, IL-10, IL-18 and serum levels of TNFα \[all picograms/milliliter(pg/ml)\] will be assessed with enzyme-linked immunosorbent assay (ELISA). Blood samples will be collected at the antecubital vein after 12-h fasting by a qualified medical professional. Serum samples will be stored in the refrigerator compartment of the laboratory of the Lithuanian Sports University at -80 degrees Celsius until further analysis.
Changes in circulating levels of Neurofilament light chain (NfL)
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Plasma levels of NfL (picograms/milliliter (pg/ml)\] will be assessed using enzyme-linked immunosorbent assay (ELISA). Blood samples will be collected at the antecubital vein after 12-h fasting by a qualified medical professional. Plasma samples will be stored in the refrigerator compartment of the laboratory of the Lithuanian Sports University at -80 degrees Celsius until further analysis.
Changes in circulating levels of tau proteins
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Plasma levels of phosphorylated tau181 (p-tau181) and total tau (t-tau) \[both, picograms/milliliter (pg/ml)\] will be assessed using enzyme-linked immunosorbent assay (ELISA). Blood samples will be collected at the at antecubital vein after 12-h fasting by a qualified medical professional. Plasma samples will be stored in the refrigerator compartment of the laboratory of the Lithuanian Sports University at -80 degrees Celsius until further analysis.
Changes in quadriceps myocellular lipid content
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
1H-MRS spectra from the right quadriceps. Outcome measures: * Quadriceps intramyocellular lipid (IMCL) content (% of unsuppressed water signal area) * Quadriceps extramyocellular lipid (EMCL) content (% of unsuppressed water signal area). * Quadriceps total IMCL and EMCL content (% of unsuppressed water signal area)
Changes in muscle contraction velocity
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Tensiomyography (TMG) of left and right rectus femoris (RF) and biceps femoris (BF) heads. Muscle contraction displacement (Dm), delay time (Td) and contraction time (Tc) will be combined to calculate contraction velocity (Vc) of left/right RF and BF. Vc = \[Dm/(Td +Tc)\] (in millimeter/second).
Changes in lower body strength and muscular endurance
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
30s Chair-Rise test: Outcome measure: number of sit-to-stand repetitions completed in 30 seconds. More sit-to-stand repetitions represents a better outcome.
Changes in circulating levels of Insulin-like growth factor 1 (IGF-1)
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Serum levels of IGF-1 \[nanograms/milliliter(pg/mL)\] will be assessed with enzyme-linked immunosorbent assay (ELISA). Blood samples will be collected at the antecubital vein after 12-h fasting by a qualified medical professional. Serum samples will be stored in the refrigerator compartment of the laboratory of the Lithuanian Sports University at -80 degrees Celsius until further analysis.
Changes in circulating levels of Irisin
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Plasma levels of irisin \[nanograms/milliliter (ng/ml)\] will be assessed using enzyme-linked immunosorbent assay (ELISA). Blood samples will be collected at the antecubital vein after 12-h fasting by a qualified medical professional. Serum samples will be stored in the refrigerator compartment of the laboratory of the Lithuanian Sports University at -80 degrees Celsius until further analysis.
Changes in brain neurometabolic levels
Time Frame: Baseline and Post-intervention time (24 weeks); Optional: follow-up at 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Single voxel proton magnetic resonance spectroscopy (1H-MRS) of left hippocampus (HPC), right dorsolateral prefrontal cortex (dlPFC) and left sensory motor cortex (SM1). Data will be processed with LC Model within the Osprey pipeline (freely available). Outcome measures will be the water-referenced levels of: * N-acetyl aspartate (NAA), * Creatine (Cr), * Choline (Cho), * Myoinositol (mIns), * Glutamine-glutamate complex (Glx), All levels are expressed in institutional units (i.u).
Changes in brain neurometabolic ratios
Time Frame: Baseline and Post-intervention time (24 weeks); Optional: follow-up at 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Single voxel proton magnetic resonance spectroscopy (1H-MRS). Ratios will be calculated from water-referenced levels of NAA, Cho, mIns, Glx, and Cr in left Hippocampus, left sensorimotor cortex and right dorsolateral prefrontal cortex. Outcome measures: * NAA/Cr, * Cho/Cr, * mIns/Cr, * Glx/Cr * NAA/mIns Ratios are expressed in arbitrary units (a.u).
Changes in knee muscle torque production
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Biodex * Maximum voluntary contraction (MVC) torque during isometric contraction in Newton/meter (N/m)., * Knee extension/flexion concentric isokinetic peak torques (PT) in N/m at isokinetic speed of 60 and 180 deg/s. * Torque development in N/m at 30ms, 50 ms, 100 ms, and 200 ms from onset of contraction.
Changes in level of fatigue
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Participants will complete the Multidimensional Fatigue Inventory (MFI-20) \[range 4-20\] with higher scores indicate a higher level of fatigue.
Changes in level of frailty
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Subjects will undergo the Edmonton Frail Scale survey \[range 0 -17\] with higher scores indicate a higher level of frailty.
Changes in nutritional status
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Participants will complete the Mini Nutritional Assessment (MNA) survey \[range 0-14\] with higher score indicate better nutritional condition.
Changes in circulating levels of beta amyloids
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Plasma levels of beta amyloid 40 (Aβ40) and beta amyloid 42 (Aβ42) will be assessed using enzyme-linked immunosorbent assay (ELISA). Blood samples will be collected at the antecubital vein after 12-h fasting by a qualified medical professional. Plasma samples will be stored in the refrigerator compartment of the laboratory of the Lithuanian Sports University at -80 degrees Celsius until further analysis. Plasma levels of Aβ40 and Aβ42 will be combined to calculate the Aβ42/40 ratio.
Changes in body composition and BMI
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
TANITA body impedance analysis. Outcome measures: total body weight, body fat mass, lean muscle mass, and bone mass (in kilograms). Total body weight and fat weight will be combined to calculate % body fat. Total body weight and height will be combined to calculate the body mass index (BMI) in kilograms/meter\^2.
Changes in health status
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Participants will complete the 36-Items Form Health survey (SF-36), \[range 0-100\] with higher score indicate better physical and mental health.
Changes in quadriceps/hamstrings cross sectional area
Time Frame: Baseline and Post-intervention time (24 weeks); Optional: follow-up at 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
T1-weighted images of the left/right thighs Outcome measures: * Quadricepscross-sectional areas at mid-thigh (in cm\^2) * Hamstring cross-sectional areas at mid-thigh (in cm\^2).
Changes in muscle contraction time
Time Frame: Baseline, Mid-intervention time (12 weeks) and Post-intervention time (24 weeks); Optional: follow-up at 48 weeks (1st follow-up) and 72 weeks (2nd follow-up) for participants who would be willing to continue their training.
Tensiomyography (TMG) of left and right rectus femoris (RF) and biceps femoris (BF) heads. Outcome measures: Delay time (Td) and contraction time (Tc) of left/right RF and BF (in milliseconds).
Secondary Outcomes
- Changes in blood count(Baseline and Post-intervention time (24 weeks); Optional follow-up at 72 weeks (2nd follow-up) for participants who would be willing to continue their training.)
- Changes in Glycosylated Hemoglobin (HbA1c)(Baseline and Post-intervention time (24 weeks); Optional follow-up at 72 weeks (2nd follow-up) for participants who would be willing to continue their training.)
- Changes in lipid profiles(Baseline and Post-intervention time (24 weeks); Optional follow-up at 72 weeks (2nd follow-up) for participants who would be willing to continue their training.)
- Self-report measure of habitual physical activity(Baseline)