‘Unlikely To Be Silver Bullet’ For Alzheimer’s, ‘No Harm In Telling High-Risk Patients To Start Exercise Plan,’ Says UT Scientist.


He called it an “exciting revelation.” A new study conducted at the Institute for Exercise and Environmental Medicine in Dallas, Texas (IEEM) showed that regularly exercising may slow down brain deterioration in people at high risk for Alzheimer’s disease.

Dr. Rong Zhang, director of the Cerebrovascular Laboratory at the IEEM, a partnership between University of Texas (UT) Southwestern and Texas Health Presbyterian Hospital Dallas, Texas, said the study found that people who had accumulation of amyloid beta in the brain experienced slower degeneration in a region of the brain crucial for memory, if they exercised regularly for one year. Also a professor of Neurology and Neurotherapeutics and Internal Medicine at UT Southwestern’s Peter O’Donnell Jr. Brain Institute, Zhang led the clinical trial that included 70 participants ages 55 and older.

“We found that it was aerobic, not stretching exercise, which reduced brain hippocampal atrophy in those who already have a lot of amyloid in their brain, a hallmark of Alzheimer’s disease,” Zhang said in an interview.

Although exercise did not prevent the eventual spread of toxic amyloid plaques blamed for killing neurons in the brains of dementia patients, researchers said the findings suggest an “intriguing possibility that aerobic workouts can at least slow down the effects of the disease if intervention occurs in the early stages.”

Currently, doctors don’t have any options for helping patients who are known to have amyloid clumping together in the brain, Zhang said adding that his findings—published in August the Journal of Alzheimer’s Disease—merit further research. “Right now, doctors can’t prescribe anything,” he said in a statement. “If these findings can be replicated in a larger trial, then maybe one day doctors will be telling high-risk patients to start an exercise plan. In fact, there’s no harm in doing so now.”

Researchers at IEEM compared cognitive function and brain volume between two groups of sedentary older adults with memory issues. One group did at least a half hour of aerobic exercise four to five times a week. The other group did only flexibility training.

“Both groups maintained similar cognitive abilities during the trial in areas such as memory and problem solving,” researchers reported. “But brain imaging showed that people from the exercise group who had amyloid buildup experienced slightly less volume reduction in their hippocampus – a memory-related brain region that progressively deteriorates as dementia takes hold.”

“It’s interesting that the brains of participants with amyloid responded more to the aerobic exercise than the others,” said Zhang. “Although the interventions didn’t stop the hippocampus from getting smaller, even slowing down the rate of atrophy through exercise could be an exciting revelation.”

Scientists all over the world are scrambling to find something, anything to help people who are suffering with dementia and its most popular form, Alzheimer’s disease. According to the World Health Organization (WHO), some 50 million people have dementia around the globe, with nearly 10 million new cases diagnosed every year. The WHO projects the number of people with dementia will reach 82 million in 2030 and 152 million by 2050. More than 5 million Americans currently have Alzheimer’s disease, and that number is expected to triple by 2050.

“Recent research has helped scientists gain a greater understanding of the molecular genesis of the disease, including a UT Southwestern discovery published last year that is guiding efforts to detect the condition before symptoms arise,” UT Southwestern reported this week. “Yet the billions of dollars spent on trying to prevent or slow dementia have yielded no proven treatments that would make an early diagnosis actionable for patients.”

In fact, pharmaceutical giant Pfizer ended its research efforts to discover new drugs for Alzheimer’s and Parkinson’s diseases in January of 2018, vaguely citing to NPR in a statement at that time that “As a result of a recent comprehensive review, we have made the decision to end our neuroscience discovery and early development efforts and re-allocate [spending] to those areas where we have strong scientific leadership and that will allow us to provide the greatest impact for patients.”

The Washington Post reported in June that Pfizer has data showing that an arthritis drug it owns called Enbrel may lower the risk of getting Alzheimer’s by 64%. “But, according to critics, Pfizer has elected not to develop the drug for this condition because the patent on it will soon expire, meaning the company won’t profit from pursuing it further,” the New Scientist reported. “Pfizer, however, denies the patent was a factor. There are ways to extend patents if something appears profitable – and, with an estimated 37 million people with Alzheimer’s worldwide, a drug for this disorder surely would be. The company told The Post that it just wasn’t convinced by the data.” Also known as etanercept, Enbrel is used to treat rheumatoid arthritis by reining in the body’s inflammatory response.

With mounting failures at finding a cure or even a treatment for Alzheimer’s disease, many researchers are looking at lifestyle modifications. In fact, in May Dr. R. Scott Turner, who directs the Memory Disorders Program at Georgetown University Medical Center, said exercise has been the only thing that has been proven to stave off Alzheimer’s disease.

But Zhang said scientists are far from giving up on finding a medication to treat the disease. “In fact, many labs and small companies are continuing their efforts to develop new ones or re-purpose old medications with multiple mechanisms and strategies, with a hope to cure or prevent Alzheimer’s,” he said.

Still scientists are less hopeful now that they will find a miracle drug to cure or treat the disease, Zhang said in an interview. “The consensus in the field, however, is that Alzheimer’s is a multi-factorial disease, thus, it is unlikely there would be a silver bullet. Exercise is a low-cost and safe polypill and has demonstrated benefits on cardiovascular health. Thus, it makes sense that exercise may reduce risk of Alzheimer’s. Of course, exercise alone may not be the only answer to prevent or treat Alzheimer’s and other chronic diseases. Medical history has told us a good lifestyle—such as exercise, diet, sleep and social engagement—is the foundation for body and mental health. But it’s possible that both exercise and medication will be helpful in dealing with debilitating diseases such as Alzheimer’s.”

When asked whether there was any data showing that Alzheimer’s numbers have grown in recent times as a result of a more sedentary computerized work environment compared to the typical work day of a century ago where, for example, more people were farmers and blue collar workers who performed much harder physical, Zhang had this to say: “This is a very intriguing question that I cannot answer without data. However, it is true that lack of physical activity in modern society is a major contributor to the prevalence of obesity, hypertension, and diabetes, which all are risks factors for Alzheimer’s.”

Zhang is among a group of scientists across the world trying to determine if exercise may be the first line of therapy to combat dementia. His latest research adds to the numerous studies suggesting links between fitness and brain health. “For example, a 2018 study showed that people with lower fitness levels experienced faster deterioration of vital nerve fibers in the brain called white matter,” UT Southwestern reported. “Research in mice has similarly shown exercise correlated with slower deterioration of the hippocampus–findings that prompted Zhang to investigate whether the same effects could be found in people.”

Zhang is leading a five-year national clinical trial that is further studying potential correlations between exercise and dementia. That trial includes six medical centers across the country and more than 600 older adults (ages 60-85) at high risk of developing Alzheimer’s disease. With it, scientists will measure whether aerobic exercise and taking specific medications—including blood pressure medicines and statins—to reduce high blood pressure and cholesterol can help preserve brain volume and cognitive abilities. Preclinical and clinical studies have suggested these medications may have benefits on brain health, he said.

Zhang said study enrollment has just been completed on the trial, and he will have more answers in two years

“Understanding the molecular basis for Alzheimer’s disease is important,” he said. “But the burning question in my field is, ‘Can we translate our growing knowledge of molecular biology into an effective treatment?’ We need to keep looking for answers.”

But he is hopeful. “I believe exercise combined with intensive treatment of cardiovascular risk factors could have a significant impact on reducing Alzheimer’s in the coming decades,” Zhang said in an interview. “Converging evidence supports this speculation. But we need to prove it.​” ​

Zhang’s study was supported by the National Institutes of Health (NIH).

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