How Exercise Might “Clean” the Alzheimer’s Brain

How Exercise Might "Clean" the Alzheimer's Brain

For the 50 million individuals worldwide ailing from Alzheimer’s disease, the announcements by pharmaceutical giants earlier this year that they will end research on therapeutics were devastating. The news is even more devastating considering projections that 100 million more people will be diagnosed with Alzheimer’s disease across the globe by 2050, all potentially without a medical means to better their quality of life.

As it happens, though, the pursuit of a therapeutic has been given a lifeline. New research shows that physical exercise can “clean up” the hostile environments in the brains of Alzheimer’s mice, allowing new nerve cells in the hippocampus, the brain structure involved in memory and learning, to enable cognitive improvements, such as learning and memory. These findings imply that pharmacological agents that enrich the hippocampal environment to boost cell growth and survival might be effective to recuperate brain health and function in human Alzheimer’s disease patients.

The brain of an individual with Alzheimer’s disease is a harsh place filled with buildups of harmful nerve cell junk—amyloid plaques and neurofibrillary tangles—and dramatic loss of nerve cells and connections that occur with severe cognitive decline, such as memory loss. Targeting and disrupting this harmful junk, specifically amyloid plaques, to restore brain function has been the basis of many failed clinical trials. This futility has led to a re-evaluation of the amyloid hypothesis—the central dogma for Alzheimer’s disease pathology based on the toxic accumulation of amyloid plaques.

At the same time, there have been traces of evidence for exercise playing a preventative role in Alzheimer’s disease, but exactly how this occurs and how to take advantage of it therapeutically has remained elusive. Exercise has been shown to create biochemical changes that fertilize the brain’s environment to mend nerve cell health. Additionally, exercise induces restorative changes relevant to Alzheimer’s disease pathology with improved nerve cell growth and connectivity in the hippocampus, a process called adult hippocampal neurogenesis. For these reasons, the authors Choi et al. explored whether exercise-induced effects and hippocampal nerve cell growth could be utilized for therapeutic purposes in Alzheimer’s disease to restore brain function.

The researchers found that exercised animals from a mouse model of Alzheimer’s had greatly enhanced memory compared to sedentary ones due to improved adult hippocampal neurogenesis and a rise in amounts of a specific molecule that promotes brain cell growth called BDNF.  Importantly, they could recover brain function, specifically memory, in mice with Alzheimer’s disease but without exercise by increasing hippocampal cell growth and BDNF levels using a combination of genetic—injecting a virus—and pharmacological means. On the other hand, blocking hippocampal neurogenesis early in Alzheimer’s worsened nerve cell health later in stages, leading to degeneration of the hippocampus and, subsequently, memory function. This provides preclinical proof of concept that a combination of drugs that increase adult hippocampal neurogenesis and BDNF levels could be disease-modifying or prevent Alzheimer’s disease altogether.

With this work, things don’t look promising for the amyloid hypothesis—that Alzheimer’s disease is caused by the deposition of amyloid plaques. In this study, it was shown that eliminating amyloid plaques were not to necessary to ameliorate memory defects, which is consistent with evidence that plaques can also be found in the brains of healthy individuals. On the contrary, we may be looking at a new and improved fundamental theory for Alzheimer’s disease based on promoting a healthier brain environment and adult hippocampal neurogenesis.

However, this inspiring news should be taken with an important caution—mouse models of Alzheimer’s are notorious for failing to translate into humans such that treatments that have worked to remedy mice have failed for humans. Besides, even if these findings translate into humans, it may apply to a fraction of Alzheimer’s individuals with relevant genetic components to the mouse model utilized. Future studies will need to replicate these results in mouse models emulating the range of known Alzheimer’s disease genetic milieus and, more importantly, prove its medical relevance to human disease.

Before translating these findings into human patients, there remains significant research to establish that a medication or drug could mimic the effects of exercise—exercise mimetics—by “cleaning up” the brain with BDNF and stimulating neurogenesis to combat Alzheimer’s disease. Currently, the method for administering BDNF to animals in the lab—by direct injection into the brain—is not ideal for use in people, and a hippocampal neurogenesis stimulating compound remains elusive.

Future attempts to generate pharmacological means to imitate and heighten the benefits of exercise—exercise mimetics—to increase adult hippocampal neurogenesis in addition to BDNF may someday provide an effective means of improving cognition in people with Alzheimer’s disease. Moreover, increasing neurogenesis in the earliest stages of the disease may protect against neuronal cell death later in the disease, providing a potentially powerful disease-modifying treatment strategy.

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Study: A Daily Baby Aspirin Has No Benefit For Healthy Older People

Daily low-dose aspirin can be of help to older people with an elevated risk for a heart attack. But for healthy older people, the risk outweighs the benefit.

Many healthy Americans take a baby aspirin every day to reduce their risk of having a heart attack, getting cancer and even possibly dementia. But is itreally a good idea?

Results released Sunday from a major study of low-dose aspirin contain a disappointing answer for older, otherwise healthy people.

“We found there was no discernible benefit of aspirin on prolonging independent, healthy life for the elderly,” says Anne Murray, a geriatrician and epidemiologist at Hennepin Healthcare in Minneapolis, who helped lead the study.

The study involved more than 19,000 people ages 65 and older in the United States and Australia. The results were published in three papers in the New England Journal of Medicine.

There is still strong evidence that a daily baby aspirin can reduce the risk that many people who have already suffered a heart attack or stroke will suffer another attack.

And there is some evidence that daily low-dose aspirin may help people younger than 70 who have at least a 10 percent risk of having a heart attack avoid a heart attack or stroke, according to the latest recommendations from the U.S. Preventive Services Task Force.

But for older, healthy people, “the risks outweigh the benefits for taking low-dose aspirin,” Murray says.

The primary risk is bleeding. The study confirmed that a daily baby aspirin increases the risk for serious, potentially life-threatening bleeding.

Surprisingly, those who took daily aspirin also appeared to be more likely to die overall, apparently from an increased risk of succumbing to cancer. That was especially unexpected given previous evidence that aspirin might reduce the risk for colorectal cancer.


Related: Panel Says Aspirin Lowers Heart Attack Risk For Some


The researchers stressed, however, that the cancer finding might have been a fluke. There’s also a possibility that any colorectal cancer benefit wasn’t seen because the subjects had only been followed for about five years.

Regardless, the findings raise serious questions as to whether otherwise healthy older people should routinely take low-dose aspirin.

“A lot of people read, ‘Well, aspirin is good for people who have heart problems. Maybe I should take it, even if they haven’t really had a heart attack,’ ” Murray says. But “for a long time there’s been a need to establish appropriate criteria for when healthy people — elderly people — need aspirin.”

That’s why the researchers launched their study, called ASPREE, in 2010. It involved 19,114 older people, with 16,703 in Australia and 2,411 in the United States. The U.S. portion included white volunteers ages 70 and older, and African-Americans and Hispanics subjects ages 65 and older.

Participants took either 100 milligrams of aspirin every day or a placebo. People in the study were followed for an average of 4.7 years.

“We were hoping that an inexpensive, very accessible medication might be something that we could recommend to elderly to maintain their independence but also decrease their risk of cardiovascular disease,” Murray says.

But based on the findings, Dr. Evan Hadley of the National Institute on Aging, which helped fund the study, says any elderly people taking aspirin or thinking about it should think twice.

“This gives pause and a reason for older people and their physician to think carefully about the decision whether to take low-dose aspirin regularly or not,” Hadley says. “And in many cases the right answer may be: Not.”

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Training for the Adult Endurance Athlete

Steve and Dr. Cole talk with Chris Palmquist to discuss the benefits of Diversified Training for Adult Endurance Athletes, how training changes over the course of a season and how a competitive adult endurance athlete trains during off-season.

Chris Palmquist is a USAT Level III and Youth/Junior Coach, USAC Level I Coach andCoachF.I.S.T. Certified Bike Fitter with 18 years of coaching experience and has coached athletes to success at the regional, national and world level.

Chris has coached elite athletes at ITU World Paratriathlon Events and High Performance Camps at Olympic Training Centers. Chris also coaches training camps for USAT JuniorsChallenged Athletes Foundation and Dare2Tri.

As an athlete, she has numerous top finishes in many sports including triathlon, collegiate rowing, canoe/kayak, cross country skiing, speed skating and road bike racing. Her coaching philosophy is based on trust, communication, balance, achieving top potential and the joy of training and racing.

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Physical Activity for Combating Chronic Inflammation in Older Adults

Image result for older athletes

Chronic inflammation is a condition contributing to development of several diseases and functional decline during aging. While regular physical activity is an important factor for healthy aging, little is known about whether it may favorably influence chronic inflammation in the elderly. These investigators studied the impact on inflammation in older women after replacing half an hour of time they spent in sedentary behavior with equal amounts of time in physical activity of different intensities.

The study shows that replacing half an hour of sedentary behavior with physical activity was related to reduced levels of inflammation. Engagement in daily physical activity of at least moderate intensity had a beneficial impact regardless of the subjects’ daily sedentary time. This supports the existence of different intensity thresholds by which physical activity may influence on chronic inflammation. These study findings were confirmed in older women among individuals with varying health status. The results support public health efforts to increase physical activity to promote health in older adults.

For more information, view the abstract

American College of Sports Medicine

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