Clinical trial NCT06252844: The Impact of 6-months of Resistance Training on Brain and Muscle Health in Older Adults With MCI
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Mild Cognitive Impairment
Older Adults at High Risk for MCI
Keywords: Mild Cognitive Impairment
Magnetic resonance imaging
Proton magnetic resonance spectroscopy (1H-MRS)
Intrinsic capacity
Mobility
Blood biomarkers
cytokines
Neuroinflammation
Systemic inflammation
Neurometabolites
Lead sponsor: Lithuanian Sports University
Sponsor class: OTHER
Collaborators: name: Lithuanian University of Health Sciences
name: KU Leuven
name: Vrije Universiteit Brussel
name: Wingate Institute
name: University of Hamburg-Eppendorf
name: Maastricht University
First posted: 2024-02-12
Enrollment: 80
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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).

Primary outcomes:
measure: Changes in intrinsic capacity
timeFrame: 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.
measure: Changes in global cognition
timeFrame: 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.
measure: Changes in psychological assessment of depression
timeFrame: 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.
measure: Changes in reaction time
timeFrame: 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.
measure: Changes in reaction accuracy
timeFrame: 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.
measure: Changes in cognitive efficiency
timeFrame: 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.
measure: Changes in Stroop interference score
timeFrame: 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.
measure: Changes in performance on the Trail Making Test (TMT)
timeFrame: 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.
measure: Changes in sway velocity
timeFrame: 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.
measure: Changes in dual-task cost for sway velocity
timeFrame: 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.
measure: Changes in agility
timeFrame: 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.
measure: Changes in lower body strength and muscular endurance
timeFrame: 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.
measure: Changes in levels of Albumin (Alb)
timeFrame: 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.
measure: Changes in levels of Hemoglobin (Hb)
timeFrame: 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.
measure: Changes in levels of C-reactive protein (CRP)
timeFrame: 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.
measure: Changes in circulating levels of cytokines
timeFrame: 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.
measure: Changes in circulating levels of Kynurenine
timeFrame: 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.
measure: Changes in circulating levels of brain-derived neurotrophic factor (BDNF)
timeFrame: 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.
measure: Changes in circulating levels of Insulin-like growth factor 1 (IGF-1)
timeFrame: 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.
measure: Changes in circulating levels of Irisin
timeFrame: 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.
measure: Changes in circulating levels of c-terminal agrin fragment-22 (CAF22)
timeFrame: 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.
measure: Changes in circulating levels of Neurofilament light chain (NfL)
timeFrame: 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.
measure: Changes in circulating levels of tau proteins
timeFrame: 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.
measure: Changes in circulating levels of beta amyloids
timeFrame: 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.
measure: Changes in brain volume properties
timeFrame: 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.
measure: Changes in brain cortical thickness
timeFrame: 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.
measure: Changes in brain WM microstructural organization
timeFrame: 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.
measure: Changes in brain neurometabolic levels
timeFrame: 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.
measure: Changes in brain neurometabolic ratios
timeFrame: 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.
measure: Changes in quadriceps/hamstrings cross sectional area
timeFrame: 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.
measure: Changes in quadriceps myocellular lipid content
timeFrame: 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.
measure: Changes in body composition and BMI
timeFrame: 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.
measure: Changes in knee muscle torque production
timeFrame: 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.
measure: Changes in muscle contraction time
timeFrame: 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.
measure: Changes in muscle contraction displacement
timeFrame: 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.
measure: Changes in muscle contraction velocity
timeFrame: 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.
measure: Changes in level of fatigue
timeFrame: 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.
measure: Changes in level of frailty
timeFrame: 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.
measure: Changes in health status
timeFrame: 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.
measure: Changes in nutritional status
timeFrame: 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.
Secondary outcomes:
measure: Changes in blood count
timeFrame: 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.
measure: Changes in lipid profiles
timeFrame: 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.
measure: Changes in Glycosylated Hemoglobin (HbA1c)
timeFrame: 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.
measure: Self-report measure of habitual physical activity
timeFrame: Baseline
Other outcomes:
Locations:
city: Kaunas
country: Lithuania
facility: Institute of Sport Science and Innovations
city: Kaunas
country: Lithuania
facility: Lithuanian Sports University
Study officials:
affiliation: Lithuanian Sports University
name: Oron Levin, PhD
role: PRINCIPAL_INVESTIGATOR
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