Effect of Exercises Training in Patients With Mild Cognitive Impairment and Early Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease; Cognitive Dysfunction
Study type: Interventional

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.
    

Intervention name(s): Aerobic exercises; Stretch exercise
Intervention type(s): Other; Other
Intervention description(s): Aerobic exercises + dual task; Stretch exercise
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Mild Cognitive Impairment; Alzheimer's disease; Aerobic exercise