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Aerobics boost brain power in mild cognitive impairment.

AT AAIC 2013

BOSTON - Combined results from two 6-month, randomized trials indicate that aerobic exercise improves executive function to a significantly greater degree than do stretching and tone exercises in patients with mild cognitive impairment or mild insulin resistance, Laura Baker, Ph.D., reported at the Alzheimer's Association International Conference 2013.

The benefits were greatest in carriers of the apo E epsilon 4 allele, which confers a higher risk for developing Alzheimer's disease.

But the "how" behind this brain boost remains something of a mystery, said Dr. Baker of Wake Forest University Winston-Salem, N.C.

"In apo E epsilon 4-negative participants, we think the mechanism is probably improved insulin sensitivity But in the apo E epsilon 4-positive patients, it seems to be some other mechanism that we don't understand."

Exercise modulates the risk of cognitive decline in numerous ways, she said. "It has a diversified portfolio of targets. Exercise exerts benefits on inflammation, improves the integrity of both macro- and microvessels, has a beneficial effect on physical and psychological stress, and modulates in flammation--all of which have been shown to have potent effects on amyloid burden."

These findings over the years have 'set the stage nicely for clinical trials. But what's the right exposure? Who are the best responders? And what is the clinical significance of the changes? Do they really translate into any improvement in quality of life?"

To try and answer some of these questions, she and her colleagues conducted two randomized physical activity trials. They recruited a total of 67 participants: 33 in a study of exercise in adults with mild cognitive impairment (MCI) and 34 with impaired insulin sensitivity who were in an identical study.

The two studies took a look at different aspects of the relationship between cognitive and metabolic health, Dr. Baker said at the meeting. "Mild metabolic disease leads to vascular dysfunction and poor glucose tolerance, which puts a person at an increased risk of mild cognitive impairment and Alzheimer's dementia."

Both studies were 6 months long and randomized participants to 45-minute sessions of either a stretch-ing/toning program or aerobic exercise, conducted four times a week. Both were held at local YMCAs and supervised by trained staff.

For the duration of the stretching program, the target heart rate was less than 35% of the maximum; the exercises also included balance and gentle yoga.

The aerobic program aimed for a heart rate of 70%-80% of maximum. It consisted of ever-increasing workouts on treadmill, stationary bike, or elliptical trainer. Adherence was very good, Dr. Baker said, with 93% of the subjects in each study completing the protocol.

Each trial had the same endpoints: tests of executive function (a composite of trail making, word fluency, symbol digit, and visual working memory) and short-term memory (story recall, list learning, and delayed matching).

The participants were a mean of 68.5 years old; altogether, 46 were randomized to the aerobic program and 21 to the stretching program. They were out of shape, Dr. Baker said, with a mean V02 peak of 22 mL/kg per minute--considered below average for that age. They were not an obese group overall, but they had a high body fat percentage of around 38%.

In the MCI study, the mean Mini-Mental State Exam score was 27. In the metabolic dysfunction study, the mean fasting glucose was 100 pg/dL and the mean fasting insulin, 11.47 mU/mL.

At the studies' ends, aerobic exercise groups had made significant gains in their cardiorespiratory fitness, as measured by improvements in the V02 peak, the treadmill incline, and the duration they could exercise. These measures were unchanged from baseline in the stretching group. The VO, peak changes were not significantly associated with executive function.

The exercise groups in both studies also experienced significant gains on the composite measure of executive function, Dr. Baker said. They had an increase of about 2 points from baseline, compared with a decline of about 3 points from baseline in the stretching group. The gains were similar whether the subjects had MCI or insulin resistance.

All of the subjects in both studies also underwent oral glucose tolerance testing at baseline and at their last visit to determine any changes in insulin resistance.

Measures of fasting glucose, fasting insulin, insulin resistance, and glucose disposal during metabolic clamp improved significantly in the exercise groups, with no difference by patient group or by apo E epsilon 4 status.

A subanalysis that controlled for insulin sensitivity examined exercise's contribution to the changes in executive function among the 52 individuals who were apo E epsilon 4 negative and the 15 who were apo E epsilon 4 positive. With the change in insulin sensitivity out of the picture, the exercise-related cognitive benefit was greater for apo E epsilon 4--positive adults," she said.

Improvements in insulin sensitivity have been associated with cognitive improvement, Dr. Baker said. However, it's not clear how this effect is mediated by apo E epsilon 4 status. "These adults with the high-risk allele show cognitive improvement that's probably related to other mechanisms."

The study has prompted a new trial, set to take place next year. The large, multicenter, randomized study will enroll 300 subjects with amnestic MCI to 18 months of moderate-to high-intensity aerobic exercise or the stretching/toning program. Exercises will again occur four times weekly.

The future trial will measure outcomes with the Alzheimer's Disease Assessment Scale--cognitive domain and the Clinical Dementia Rating-sum of boxes, and performance on computerized tests of memory.

This trial will also include MRI and cerebrospinal fluid biomarker data obtained at baseline and study's end.

On Twitter @alz_gal

Caption: At the studies' ends, participants in the aerobic exercise group had made significant gains in the composite measure of executive function.

Caption: Dr. Laura Baker says the mechanism is likely "improved insulin sensitivity."


Major finding: Individuals who performed aerobic exercises had a significant increase of about 2 points from baseline on a composite measure of executive function, compared with a decline of about 3 points from baseline in those who performed stretching and toning exercises, regardless of whether the subjects had MCI or insulin resistance.

Data source: Two 6-month studies that randomized a total of 67 patients to either aerobic exercise or stretching and toning exercises.

Disclosures: Dr. Baker had no financial disclosures. The studies were funded by the Alzheimer's Association, the America Diabetes Association, and the National Institute on Aging.
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Title Annotation:NEUROLOGY
Author:Sullivan, Michele G.
Publication:Clinical Psychiatry News
Date:Feb 1, 2014
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