Megan Brooks

November 12, 2015

BARCELONA — Six months of aerobic exercise led to increased blood flow in the brain and reduced levels of phosphorylated tau protein levels in cerebrospinal fluid (CSF) in adults with mild cognitive impairment (MCI) and prediabetes.

The findings provide more evidence that aerobic exercise "holds promise as a disease-modifying therapeutic intervention" for adults in the earliest stages of Alzheimer's disease (AD), the researchers say.

Laura Baker, PhD, principal investigator and cognitive neuroscientist at Wake Forest School of Medicine, Winston-Salem, North Carolina, reported the findings at the 8th Clinical Trials Conference on Alzheimer's Disease (CTAD).

Multiple Favorable Effects

High tau protein levels in the brain are associated with progression to AD. "Thus, identifying interventions that can successfully reduce these levels has become a priority in clinical treatment trials," Dr Baker and colleagues note in their conference abstract. In prior studies, they and others have shown that aerobic exercise has favorable effects on cognitive function and plasma levels of β amyloid.

In the current study, Dr Baker and colleagues tested the effects of aerobic exercise on CSF levels of tau and β amyloid in 65 adults aged 55 to 89 years with MCI and prediabetes based on American Diabetes Association blood hemoglobin A1c criteria.

Participants were randomly assigned to a structured exercise program that was supervised by a trainer and involved moderate- to high-intensity aerobics or stretching for 45 to 60 minutes, four times per week for 6 months. The aerobic group exercised at 70% to 80% of heart rate reserve, while the stretching (control) group exercised at an intensity below 35% heart rate reserve.

At the beginning and end of the study, CSF and blood were collected and all participants completed standard cognitive and physical fitness assessments. Forty participants also underwent brain MRI.

Adherence to the intervention protocols was high (92%), the researchers report. At 6 months, participants in the aerobic exercise group showed improved walk times and glucose tolerance relative to their peers in the stretching (control) group (P < .05).

Six months of structured moderate- to high-intensity aerobic exercise also reduced CSF levels of phosphorylated and total tau protein, especially in adults older than age 70 years (P < .05), they say.

Aerobic exercise was further associated with increases in blood flow in the right anteromedial temporal lobe region (P < .05) and favorable effects on a composite measure of executive function (P < .05).

"Resting blood flow was increased in those areas of brain where blood flow is typically decreased with aging and with the onset and progression of MCI due to Alzheimer's disease," Dr Baker said in a conference news release. "The question we are going to ask next is whether the increased blood flow reflects improved health of the vessels in specific regions of the brain, or increased volume of blood to these regions."

The researchers say the next phase of the study will extend the exercise program to 18 months and will be conducted under the auspices of the Alzheimer's Disease Cooperative Study at 14 sites in the United States.

Dr Baker said she is hopeful that the results of the study will help motivate people to think about exercise in a different way. "We all know that exercise is good for us, but maybe seeing observable, objective brain changes will provide the impetus to get us out the door to exercise," she said in the release.

"Important" Study

"This is an extremely important study," Majid Fotuhi, MD, PhD, medical director, NeuroGrow Brain Fitness Center, McLean, Virginia, and Johns Hopkins Medicine, Baltimore, Maryland, told Medscape Medical News.

"Exercise has been shown to increase blood flow to the brain, but nobody has found solid evidence that it can actually reduce the level of tau, which is the most important biomarker for Alzheimer's disease. Many pharmaceutical companies have tried hard to come up with a drug to reduce the load of tau in the brain, and they have not been successful so far," added Dr Fotuhi, who was not involved in the study.

Cyrus Raji, MD, PhD, from the University of California, Los Angeles, who also didn't participate in the study, told Medscape Medical News he "likes the molecular approach this abstract takes and the 92% adherence rate shows you can get people to stick with these exercise programs."

The study was funded by the American Diabetes Association, Alzheimer's Association, National Institute on Aging, Department of Veterans Affairs and Wake Forest School of Medicine. The authors have disclosed no relevant financial relationships.

8th Clinical Trials Conference on Alzheimer's Disease (CTAD). Abstract OC30. Presented November 6, 2015.


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