Clinical trial NCT02074215: Effect of Exercises Training in Patients With Mild Cognitive Impairment and Early Alzheimer's Disease
Official title: Effects and Mechanisms of Aerobic Exercises Combined With Dual-task Training in Cognitive Function in Patients With Mild Cognitive Impairment and Early Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alzheimer's Disease
Keywords: Mild Cognitive Impairment
Alzheimer's disease
Aerobic exercise
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2014-02-28
Enrollment: 19
Sex: ALL
Minimum age (years): 60
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Recent studies have shown that aerobic exercises and dual-task training are effective in improving overall cognitive function in patients with cognitive impairment or dementia. However, the biological mechanisms are unknown in humans. It also remains unclear regarding whether carrying APOEε4 genotype or not would influence the effects. Therefore, the three main purposes of this study are: (1) to investigate the effects of a 3-month aerobic exercises combined with dual-task training on memory and executive cognitive functions in patients with mild cognitive impairment (MCI) and in those with early Alzheimer's disease (AD); (2) to compare the differences in training effects between patients who carry APOEε4 genotype and those who do not carry this genotype; and (3) to investigate the biological mechanisms of the exercise training effects on memory and executive cognitive function in these patients. The biological mechanisms of interest will include the blood Aβ1-40 and Aβ1-42 level, insulin, fasting glucose, cytokine, integrity of brain fiber tracts, and cerebral blood flow.

We will conduct a randomized controlled clinical trial. A total of 70 patients with MCI or AD will be recruited. The participants will be randomly assigned to the experimental group or the control group. Both groups will receive three 90-minute exercise sessions per week for 12 weeks. For the experimental group, the exercise program will include moderate intensity aerobic exercises and dual-task training; whereas for the control group, the training program will include gentle stretching exercises. Both groups will receive examinations on outcome variables, including blood Aβ1-40 and Aβ1-42 level, insulin, fasting glucose, cytokine,integrity of brain fiber tracts, cerebral blood flow, cognitive function, and dual task performance at baseline, post-training, and after a 3-month follow-up period. Differences on the aforementioned outcomes brought by the 12-week training programs will be compared between the experimental and control groups. Exercise effects between patients who carry APOEε4 genotype and those who do not will also be examined.

Results of this study will provide relevant clinical evidence for the effects of aerobic exercises combined with dual-task training on patients with MCI and mild AD; and will provide further understanding of the mechanisms mediating these effects.

Detailed description: Recent studies have shown that moderate-to-high intensity aerobic exercises are effective in improving overall cognitive function in patients with cognitive impairment or dementia. Dual-task training programs also show positive effects on enhancing executive function in patients with cognitive impairment. However, the biological mechanisms through which these training effects are mediated remain largely unknown in humans. It also remains unclear regarding whether carrying APOEε4 genotype or not would influence the effects of aerobic exercises and dual-task training on cognitive function of these patients. Therefore, the three main purposes of this study are:

1. to investigate the effects of a 3-month aerobic exercises combined with dual-task training on memory and executive cognitive functions in patients with mild cognitive impairment (MCI) and in those with early Alzheimer's disease (AD);
2. to compare the differences in training effects between patients who carry APOEε4 genotype and those who do not carry this genotype; and
3. to investigate the biological mechanisms of the exercise training effects on memory and executive cognitive function in these patients. The biological mechanisms of interest will include the blood Aβ1-40 and Aβ1-42 level, insulin, fasting glucose, cytokine (TNF-α, Interleukin(IL) -Iβ, IL-6, CRP),integrity of brain fiber tracts, and cerebral blood flow.

We will conduct a single-blind (assessor blinded) randomized controlled clinical trial. A total of 70 patients with MCI or AD will be recruited. The participants will be randomly assigned to the experimental group or the control group using stratified randomization by matching patient's diagnosis. Both groups will receive one health education session and three 90-minute exercise sessions per week for 12 weeks. For the experimental group, the exercise program will include moderate intensity aerobic exercises and dual-task training; whereas for the control group, the training program will include gentle stretching exercises and activities in sitting of mild intensity. Both groups will receive examinations on outcome variables, including blood Aβ1-40 and Aβ1-42 level, insulin, fasting glucose, cytokine (TNF-α, IL-Iβ, IL-6, CRP),integrity of brain fiber tracts, cerebral blood flow, cognitive function, and dual task performance at baseline, post-training, and after a 3-month follow-up period. Differences on the aforementioned outcomes brought by the 12-week training programs will be compared between the experimental and control groups using two-way (group x time) repeated measures of ANOVA. Intercorrelations among the changes in these outcomes will be analyzed to explore the possible biological mechanisms mediating the training effects. Exercise effects between patients who carry APOEε4 genotype and those who do not will also be examined.

Results of this study will provide relevant clinical evidence for the effects of aerobic exercises combined with dual-task training on patients with MCI and mild AD; and will provide further understanding of the mechanisms mediating these effects.

Eligibility criteria: Inclusion Criteria:

* mild cognitive impairment or mild AD.

Exclusion Criteria:

* neurological disorders or psychiatric disorders, or any other systematic diseases that would affect their walking ability

Primary outcomes:
measure: Changes of Memory and executive function related neuropsychological test
timeFrame: Changes from baseline in neuropsychological test at 3 months and 6 months
Secondary outcomes:
measure: Changes of muscle strength of upper and lower extremity and walking speed
timeFrame: Changes from baseline in muscle strength of upper and lower extremity and walking speed at 3 months and 6 months
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Ming-Jang Chiu, PhD
role: STUDY_CHAIR
References: