The Impact of 6-months of Resistance Training on Brain and Muscle Health in Older Adults With MCI

NCT ID: NCT06252844

Last Updated: 2024-02-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-15
• Study Completion Date: 2025-12-31

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.

Conditions

Mild Cognitive Impairment; Older Adults at High Risk for MCI

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Intervention

Progressive resistance training (PRT) of lower limb muscles. Frequency of intervention: 2-3 times per week. Duration of intervention: 24 weeks.

Group Type: EXPERIMENTAL

Resistance exercise training

Intervention Type: BEHAVIORAL

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.

Active control

Flexibility training of the lower limb muscles. Frequency of intervention: 2-3 times per week. Duration of intervention: 24 weeks.

Group Type: EXPERIMENTAL

Active control

Intervention Type: BEHAVIORAL

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.

Interventions

Resistance exercise training

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.

Intervention Type: BEHAVIORAL

Active control

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.

Intervention Type: BEHAVIORAL

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).

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Lithuanian University of Health Sciences

OTHER

Sponsor Role: collaborator

KU Leuven

OTHER

Sponsor Role: collaborator

Vrije Universiteit Brussel

OTHER

Sponsor Role: collaborator

Wingate Institute

OTHER

Sponsor Role: collaborator

University of Hamburg-Eppendorf

OTHER

Sponsor Role: collaborator

Maastricht University

OTHER

Sponsor Role: collaborator

Lithuanian Sports University

OTHER

Sponsor Role: lead

Responsible Party

Vilma Dudoniene

Prof. Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Oron Levin, PhD

Role: PRINCIPAL_INVESTIGATOR

Lithuanian Sports University

Locations

Institute of Sport Science and Innovations

Kaunas, , Lithuania

Site Status: RECRUITING

Lithuanian Sports University

Kaunas, , Lithuania

Site Status: RECRUITING

Countries

Lithuania

Central Contacts

Vida J Česnaitienė, PhD

Role: CONTACT

vida.cesnaitiene@lsu.lt

+370 698 33646

Facility Contacts

Nerijus Masiulis, PhD

Role: primary

nerijus.masiulis@lsu.lt

+370 60039099

Vilma Dudoniene, PhD

Role: primary

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Related Links

https://apps.who.int/iris/bitstream/handle/10665/326843/WHOFWC-ALC-19.1-eng.pdf?sequence=17&isAllowed=y

Guidance on person-centred assessment and pathways in primary care

https://doi.org/10.1519/jsc.0000000000003230

Resistance Training for Older Adults: Position Statement From the National Strength and Conditioning Association

Other Identifiers

LithuanianSportsU-18

Identifier Type: -

Identifier Source: org_study_id