Effects of Combined Physical-cognitive Training on Cognitive Function in MCI

Study Overview
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Brief Summary
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The present study aims to investigate the effects of combined physical-cognitive training on cognitive function as well as peripheral BDNF level and mitochondrial function of individuals with MCI. It is hypothesized that: 1) the combined physical-cognitive training program will be superior to the physical and cognitive training program alone; and 2) the degree of cognitive improvement will be positively correlated with the improvement of plasma BDNF and mitochondrial function.

Detailed Description
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Recent research suggests that the benefits of combined physical-cognitive training may be greater than either physical or cognitive training alone. Nevertheless, this synergistic effect has been demonstrated mainly in cognitively intact older adults. Studies examining the effects of combined physical-cognitive training in older adults with MCI are scarce and show mixed results. Moreover, few studies have determined the effects of the combined training on peripheral brain-derived neurotrophic factor (BDNF) and mitochondrial function. Thus, the present study aims to investigate the effects of combined physical-cognitive training on cognitive function as well as peripheral BDNF level and mitochondrial function of individuals with MCI. The present study will provide insight into the interplay among the training program, peripheral BDNF concentration, mitochondrial function, and cognitive function. Importantly, the findings will have clinical implication regarding the training program that is feasible and effective in improving cognitive function of older adults with MCI which ultimately will have great impact on public health as this population is at high risk of progression to AD.

Official Title
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Synergistic Effects of Combined Physical-cognitive Training on Cognitive Function in Individuals With Mild Cognitive Impairment (MCI): A Randomized Controlled Trial

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Other: Combined physical-cognitive training
* Other: Physical training
* Other: Cognitive training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: meet criteria for mNCD (mild neurocognitive disorders), previously known as MCI, based on the recent DSM-V (Diagnostic Statistical Manual-V) criteria comprehend instructions and willing to participate able to comply with the study schedule and procedures not taking any medications for their cognition and not planning to start medications during the study trial Exclusion Criteria: presence of medical conditions that would be unsafe to exercise diagnosed with other neurological conditions (e.g. Parkinson's disease, Stroke, Multiple Sclerosis, AD) that affect cognition and mobility presence of depressive symptoms presence of acute or/and chronic disease that could not be controlled (e.g. Arthritis, Asthma, Hypertension, Diabetes mellitus, Coronary artery disease) exercise regularly (at least 30 min/day, 3 days/week)

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Phys Group<br>physical training group | Other: Physical training<br>* Multi-component physical exercise<br>|
| Active Comparator: Cog Group<br>cognitive training group | Other: Cognitive training<br>* cognitive training<br>|
| Experimental: Phys-Cog Group<br>combined physical-cognitive training group | Other: Combined physical-cognitive training<br>* combined physical-cognitive training<br>|
| No Intervention: Con Group<br>educational control group | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline Alzheimer's Disease Assessment- cognitive subscale at 3 months | Alzheimer's Disease Assessment-cognitive subscale will be assessed at baseline and 3 months. The total scores range from 0-70, with higher scores (≥ 18) indicating greater cognitive impairment. | 3 months | 
| change from baseline Rey auditory verbal learning score at 3 months | Memory will be assessed using Rey auditory verbal learning test. | 3 months | 
| change from baseline Trail Making B-A score at 3 months | Executive function will be assessed using Trail Making Test part B-A. | 3 months | 
| change from baseline brain-derived neurotrophic factor level at 3 months | Level of plasma brain-derived neurotrophic factor (BDNF) will be determined. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline Digit Span score at 3 months | Attention will be assessed using Digit Span forward-backward test. | 3 months | 
| change from baseline stepping response time at 3 months | Processing speed will be measured using stepping response time. | 3 months | 
| change from baseline time to complete Timed Up and Go at 3 months | Functional ability will be assessed using time to complete Timed Up and Go (TUG). | 3 months | 
| change from baseline physiological profile assessment score at 3 months | Fall risk will be assessed using the physiological profile assessment. The test consists of five sensorimotor and balance measures including visual contrast sensitivity, proprioception, quadriceps muscle strength, hand reaction time, and postural sway. The five PPA components are weighted to compute a composite z-score distribution with high scores indicating increased fall risk. | 3 months | 
| change from baseline mitochondrial oxygen consumption rate at 3 months | Mitochondrial function will be determined from oxygen consumption rate (OCR) | 3 months | 
| change from baseline mitochondrial reactive oxygen species (ROS) level at 3 months | Mitochondrial function will be determined from reactive oxygen species (ROS) level | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mild cognitive impairment, combined physical-cognitive training, BDNF, mitochondrial function, cognitive function