Laird Harrison

June 02, 2017

DENVER — Aerobic exercise can reverse the cognitive decline typical of Alzheimer's disease, at least in the short term, a new meta-analysis suggests.

"It's not a huge improvement, but to be able to say there is any improvement is a pretty big deal," said Gregory Panza, a PhD candidate from the University of Connecticut in Hartford.

This meta-analysis is the first to suggest that aerobic activity is more effective in reversing Alzheimer's disease than resistance training. "What this can do is target the types of intervention that need to be given," Panza told Medscape Medical News.

Because it has been shown that exercise can improve cognitive abilities in healthy people, many public health organizations, including the World Health Organization, recommend exercise as a therapy for people with Alzheimer's disease.

But trials have produced mixed results, and most attempts to aggregate data from these trials have not used the best statistical methods, Panza said. In fact, some meta-analyses have combined Alzheimer's disease with other forms of dementia, even though the disorders have different causes.

To examine which types of exercise produce the most benefit, Panza and his colleagues looked at 914 potentially relevant studies. They zeroed in on studies that used exercise as the only intervention, had a nonexercise control group, measured cognitive impairment, and involved people diagnosed with or at risk for Alzheimer's disease who were at least 19 years of age.

Panza presented the findings here at the American College of Sports Medicine 2017 Annual Meeting.

The team identified 19 studies with 1145 participants that met their criteria. Eleven of these studies looked at people diagnosed with Alzheimer's disease and eight looked at people at risk. People considered to be at risk for Alzheimer's disease had mild cognitive impairment, a genetic risk for the disease, or a biological parent with an Alzheimer's diagnosis.

Eighteen of the studies were published after 2001, and one study was unpublished.

There were 23 exercise subgroups in the 19 studies: 15 that used aerobic exercise as the only intervention, one that used resistance training as the only intervention, and seven that combined the two types of exercise.

In the exercise groups, participants exercised, on average, 140 minutes per week, spread over 3.4 days, at an intensity of 3.7 metabolic equivalents of task (METs) (1 MET equals 1 kcal/kg of body weight per hour, or roughly the amount of energy expended while sitting quietly).

The control subgroups involved a variety of protocols. Participants were assigned to standard care in 15 cases, stretching in three, planned social visits in two, chair-based range-of-motion exercises in one, diet and exercise education in one, and a waiting list in one.

Panza and his colleagues used a modified version of the Downs and Black Checklist to assess the quality of the studies. Study ratings ranged from 17 to 23 of a possible 26 points, with an average of 20.3.

To calculate effect size, the team divided the difference in mean cognitive score between the exercise and control groups by the pooled standard deviation. Effect sizes of 0.20 were considered small, 0.50 were considered medium, and 0.80 were considered large.

Aerobic Training

For aerobic training, the effect size was a statistically significant 0.65 (95% confidence interval [CI], 0.35 - 0.95). For the combination of aerobic and resistance training, the effect size, of 0.19, was not significant (95% CI, –0.06 to 0.43).

People who attended a higher proportion of the exercise sessions saw greater improvements in cognitive function.

Not only did participants in exercise groups perform better than those in control groups on cognitive tests, their scores after exercise were better than their own baseline scores, which suggests improvement over time. The effect size of this improvement was 0.20 (95% CI, 0.11 - 0.28).

In contrast, the cognitive performance of the people in the control groups declined, with an effect size of –0.18 (95% CI, –0.37 to 0.00).

All of the effects remained significant after diagnosis and age were controlled for (P ≤ 0.036 for all).

It is not clear why aerobic exercise improves cognitive performance in people with or at risk for Alzheimer's disease. "The physiologic mechanism of Alzheimer's is not known, so it's kind of hard to say," Panza explained. He pointed out that exercise can stimulate the release of serotonin and brain-derived neurotrophic factor, which could affect cognitive function.

There is some evidence that exercise can affect neuroplasticity, said Carson Smith, PhD, from the University of Maryland in College Park.

Aerobic exercise might help more than resistance exercise because "it seems important to drive the cardiovascular system to the point where there are adaptations," he told Medscape Medical News.

But longer-term data will be needed to show whether these changes can be maintained. "Convincing evidence that exercise is a cure for Alzheimer's is lacking," he pointed out.

On average, the interventions lasted 18 weeks, Panza reported, so "more longitudinal studies need to be done."

Still, it is unlikely that patients with Alzheimer's disease will be able to stave off symptoms indefinitely with exercise. "There is no cure," he pointed out. "It just kind of delays the inevitable."

The study was funded by the InCHIP Healthy Habits Systematic Review Project. Mr Panza and Dr Smith have disclosed no relevant financial relationships.

American College of Sports Medicine (ACSM) 2017 Annual Meeting: Abstract 843/22. Presented May 31, 2017.

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