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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
80
Supervised PRT will consist of leg extension, leg curl, leg press, and calf raises. Initially participants will start with a 4 weeks adaptation with low loads at 15 (repetition maximum, RM) conducting for 1-3 sets. Further on subjects will continue with a 5 month of PRT with intensity increasing every 2 weeks from 12 to 6 RM. Each exercise will be done for 3 sets with 2 min rest periods between sets. After the 2 weeks at 6 RM, 1 week of rest will be applied. After the rest week, the same cycle starting from 12 RM will be repeated until the end of intervention.
Supervised static stretching exercises will be performed without causing an unpleasant feeling of stretching, up to pain, maintaining the stretching position for at least 30 s. Exercises will be performed slowly so that heart rate (HR) does not exceed 50% maximum. Subjects will calculate their HR before training, in the middle and after the training measuring the pulse for 10 s. Exercises will be repeated 3-5 times for each side of the body. The duration of the training will be match to PRT group and will take around 40 min. In order to keep the subjects interested and motivated, two of the stretching exercises will be changed every two weeks.
Institute of Sport Science and Innovations
Kaunas, Lithuania
RECRUITINGLithuanian Sports University
Kaunas, Lithuania
RECRUITINGChanges in intrinsic capacity
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.
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.
Changes in global cognition
Outcome measure: scores on the Montreal cognitive assessment (MoCA) \[range 0 - 30\] with higher scores indicating better performance.
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.
Changes in psychological assessment of depression
Outcome measure: scores on the Geriatric depression scale (GDS), \[range 0-15\] with higher score indicate severe 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.
Changes in reaction time
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.
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.
Changes in reaction accuracy
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.
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.
Changes in cognitive efficiency
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
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.
Changes in Stroop interference score
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.
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.
Changes in performance on the Trail Making Test (TMT)
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.
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.
Changes in sway velocity
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.
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.
Changes in dual-task cost for sway velocity
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.
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.
Changes in agility
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.
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.
Changes in lower body strength and muscular endurance
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.
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.
Changes in levels of Albumin (Alb)
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.
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.
Changes in levels of Hemoglobin (Hb)
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.
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.
Changes in levels of C-reactive protein (CRP)
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.
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.
Changes in circulating levels of cytokines
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.
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.
Changes in circulating levels of Kynurenine
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.
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.
Changes in circulating levels of brain-derived neurotrophic factor (BDNF)
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.
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.
Changes in circulating levels of Insulin-like growth factor 1 (IGF-1)
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.
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.
Changes in circulating levels of Irisin
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.
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.
Changes in circulating levels of c-terminal agrin fragment-22 (CAF22)
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.
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.
Changes in circulating levels of Neurofilament light chain (NfL)
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.
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.
Changes in circulating levels of tau proteins
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.
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.
Changes in circulating levels of beta amyloids
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.
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.
Changes in brain volume properties
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).
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.
Changes in brain cortical thickness
Whole brain T1-weighted images. Outcome measures: GM cortical thicknesses (in mm) of cortical substructures. Image processing: FreeSurfer software, version 6 (freely available).
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.
Changes in brain WM microstructural organization
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).
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.
Changes in brain neurometabolic levels
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).
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.
Changes in brain neurometabolic ratios
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).
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.
Changes in quadriceps/hamstrings cross sectional area
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).
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.
Changes in quadriceps myocellular lipid content
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)
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.
Changes in body composition and BMI
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.
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.
Changes in knee muscle torque production
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.
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.
Changes in muscle contraction time
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).
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.
Changes in muscle contraction displacement
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).
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.
Changes in muscle contraction velocity
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).
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.
Changes in level of fatigue
Participants will complete the Multidimensional Fatigue Inventory (MFI-20) \[range 4-20\] with higher scores indicate a higher 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.
Changes in level of frailty
Subjects will undergo the Edmonton Frail Scale survey \[range 0 -17\] with higher scores indicate a higher 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.
Changes in health status
Participants will complete the 36-Items Form Health survey (SF-36), \[range 0-100\] with higher score indicate better physical and mental health.
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.
Changes in nutritional status
Participants will complete the Mini Nutritional Assessment (MNA) survey \[range 0-14\] with higher score indicate better nutritional condition.
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.
Changes in blood count
Blood count tests will be conducted using GBC-system XN-1500 blood analyzer. Blood samples will be collected at the antecubital vein after 12-h fasting by a qualified medical professional. Outcome measures: * Red blood cell count measured in cells per liter (cells/L). Normal range \[Male: 4.35 x 10\^12 to 5.65 x 10\^12 cells/L; Female: 3.92 x 10\^12 to 5.13 x 10\^12 cells/L\]. * White blood cell count measured in cells per liter (cells/L). Normal range \[3.4 x 10\^9 to 9.6 x 10\^9 cells/L\]. * Platelet count measured in cells per liter (cells/L). Normal range \[Male: 135 x 10\^9 to 317 10\^9 cells/L; Female: 157 x 10\^9 to 371x10\^9 cells/L\]. * Hematocrit (percentage by volume of red cells). Normal range \[Male: 38.3% to 48.6%; Female: 35.5% to 44.9%\].
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.
Changes in lipid profiles
A lipidogram test will be conducted using COBAS PRO blood analyzer. Blood samples will be collected at the antecubital vein after 12-h fasting by a qualified medical professional. Outcome measures: * Level of HDL (high-density lipoprotein) cholesterol \[millimole/liter (mmol/L)\]. Normal range \< 1.68 mmol/L * Level of LDL (high-density lipoprotein) cholesterol. Normal range \< 2.59 mmol/L. * Level of total cholesterol. Normal range \< 5.2 mmol/L * Level of Triglycerides. Normal range \< 1.7 mmol/L
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.
Changes in Glycosylated Hemoglobin (HbA1c)
Glycosylated Hemoglobin levels will be measured using the Alinity C method. Blood samples will be collected at the antecubital vein after 12-h fasting by a qualified medical professional. Outcome measures: \- Level of HbA1c \[millimole/liter (mmol/L)\]. Normal range \< 42 mmol/L (\~ 6%).
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.
Self-report measure of habitual physical activity
Participants will complete the International Physical Activity Questionnaire (IPAQ-LT). Higher score indicate high physical activity level.
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Time frame: Baseline