Efficacy of Aerobic Exercises Combined with Dual-task Training on Body Structure and Body Function, Activity, and Social Participation in Patients with Mild Cognitive Impairment and Patients with Early Alzheimer's Disease

Recent studies have shown that moderate-to-high intensity aerobic exercises are effective in improving overall cognitive function in patients with cognitive impairment and dementia. Dual-task training programs also show positive effects on enhancing executive function in patients with cognitive impairment. However, the mechanisms through which these training effects are mediated remain largely unknown in humans. It also yet to be explored as to whether patients with different levels of dementia or carrying different apolipoprotein E（APOE）genotypes would benefit from aerobic exercises or dual-task training differentially. Therefore, the purposes of this study were: (1) to investigate the effects of a 3-month moderate intensity aerobic exercises combined with dual-task training on body structure and body function (insulin resistance, tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6, C-reactive protein (CRP), basilar artery resistance, cingulum bundle integrity, cognitive function, motor function, and depression), activity (level of physical activity, physical frailty, level of disability), and participation (quality of life and social participation) in patients with mild cognitive impairment (MCI) and in those with early Alzheimer’s disease (AD); (2) to compare the differences in exercise training effects between patients with MCI and patients with AD, and between patients carrying and not carrying APOEε4 genotype; and (3) to investigate the correlations of changes in cognitive functions with changes in insulin resistance, TNF-α, IL-6, CRP, basilar artery resistance, and cingulum bundle integrity, after training in order to explore the possible neuroanatomical and neurophysiological mechanisms of exercise training effects.
We conducted an assessor-blind randomized controlled clinical trial. A total of 18 patients with MCI or AD were recruited. The participants were randomly assigned to the aerobic exercise training group (aerobic group) or the stretch control group (stretch group) using the stratified randomization by matching patient’s diagnosis. The both aerobic and stretch group received health education and exercises training for 12 weeks. The aerobic group received three 90-minuate group exercises sessions, that included aerobic exercises combined with dual-task training, and two 30-minute individual walking exercise sessions at home per week. The stretch group received three 90-minuate group exercise sessions that included stretch exercises and activities in sitting. Both groups received examinations on primary outcomes (including insulin resistance, TNF-α, IL-6, CRP, basilar artery resistance, cingulum bundle integrity, cognitive function, and motor performance) and secondary outcomes (including depression, physical activity level, physical frailty, level of disability, social participation, and quality of life) at baseline (week 0) and post-training (week 12). Differences on the aforementioned outcomes brought by the 12-week exercise training programs were compared between and within the aerobic and stretch groups using Mann-Whitney U Test and Wilcoxon Signed Ranks Test, respectively. Correlations of changes in cognitive functions with changes in insulin resistance, TNF-α, IL-6, CRP, basilar artery resistance, and cingulum bundle integrity were analyzed using Spearman rank correlation coefficient to explore the possible neural or physiological mechanisms mediating the exercise training effects. Exercise effects between patients with MCI versus AD and between patients carrying and not carrying APOEε4 were also examined.
The results showed that the educational level of the stretch group was higher than the aerobic group. There were significant differences between the aerobic and stretch group in the time of chair rise test before taining. The aerobic group showed a significant increase in muscle strength of upper and lower extremities and improvement in dual-task walking performance after 3 months of training. The stretch group showed a significant increase in the matrix reasoning score and decrease in Alzheimer’s Disease Assessment Scale -Cognitive Subscale (ADAS-cog) and level of depression after 3 months of training. After 3 months of training, the aerobic group showed greater integrity of anterior and middle cingulum bundles of the left hemisphere and better performance of Modified Card Sorting Test (MCST) than stretch group.
Patients with AD had poorer cognitive function than the patients with MCI before training. The effects of exercise training were greater for the early AD subjects than for the MCI subjects, especially in muscle strength and memory function. The APOEε4 noncarriers had poorer cognitive function than the APOEε4 carriers at baseline. The APOEε4 noncarriers had greater improvement in matrix reasoning test than the APOEε4 carriers after exercise training.
Both aerobic exercise combined dual-task training and stretch exercise training were effective in improving cognitive or motor function of patients with MCI and early AD. These effects of exercise training were greater in patients with early AD, especially in those APOEε4 noncarriers, than in patients with MCI or AD with APOEε4. Early exercise intervention is therefore suggested to patients with MCI and early AD in order to maintain or improve their cognitive and motor functions.