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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Marathon Training and Recovery Tips

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Dr. Gregory Nicholson from Midwest Orthopaedics at Rush and Steve Kashul talk with Jaime Ginsberg, DPT from ATI Physical Therapy about marathon training and recovery. Jaime is a 2 time Ironman Triathlon Finisher and has run in 15 marathons. She specializes in treating runners and triathletes, practicing for over 17 years.

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Dealing with Anterior Cruciate Ligament Injury

By Jess Walter

Anterior cruciate ligament (ACL) injuries are common in sports such as football, basketball, netball, and alpine skiing. They have a big impact on athletic performance, because approximately 79% of people go on to develop knee osteoarthritis after an ACL tear. A study by T Nessler et al called ACL Injury Prevention: What Does Research Tell Us? stresses the importance of ACL injury prevention as a way to avoid the long-term effects of this injury. It all begins in youth – programs which utilize neuromuscular training and strength training at a young age show the most promise in reducing ACL injuries.

What Does An ACL Injury Involve?

The anterior cruciate ligaments (ACL) is found inside the knee joint. It provides the knee with rotational stability and stops the tibia from sliding out in front of the femur. An ACL injury occurs when this ligament is torn, most during sports that involve sudden stops, changes in direction, or jumps. Its symptoms include a popping sensations in the knee, severe pain and inability to continue practicing sport, swelling, a reduced range of motion, and the knee giving weight when bearing weight or playing one’s normal sport.

How Can ACL Injuries Be Prevented?

As mentioned above, the earlier neuromuscular and strength training take place, the better. Prevention programs show a high success rate (52% in female athletes and 85% in male athletes) when preventive programs are adopted. There are six important components of a prevention program: early age; correct sports movements; consistency of sessions; frequency (sessions should last 20 to 30 minutes and commence pre-season), feedback; and exercise variety. There are three main components of an ACL prevention program: plyometrics (focusing on good technique in movement); neuromuscular training (which work on balance and stability); and strength training combined with resistance training.

What Treatments Exist for ACL Injuries?

Treatment for ACL usually involves several weeks of rehabilitation involving exercises provided by a physiotherapist. Injury is sometimes recommended for athletes who will need to perform jumping, pivoting and cutting movements regularly, or for those who have more than one ligament or cartilage injured. During surgery the damaged ligament is removed and replaced with a tendon graft taken from a donor or from another part of the knee. New tissue then grows over this graft. The process of recovery is long and can take between eight and 12 months of rehabilitation.

If you are a professional athlete, ACL prevention is key, simply because treatment is long and the reinjury rate is high. Studies have shown that around 2.3% to 13% of those operated can have a similar injury after surgery. The knee joint is a complex network of tendons, bones, and ligaments so if you are in pain, it is vital to determine the exact cause of the problem so treatment can commence. From an early age, athletes should undertake exercises focusing on strength, balance, and stability, to enjoy their sport in an injury- and pain-free manner.

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Passage of Sports Medicine Clarity Act Improves Care for All Athletes

The American Orthopaedic Society for Sports Medicine (AOSSM) is proud to have been part of the process to cross the finish line with the passage of the Sports Medicine Licensure Clarity Act (H.R.302) which was signed into law this week as part of the FAA Reauthorization Act of 2018. The legislation provides legal protection for traveling team physicians and safeguards injured athletes’ timely access to the health care professionals who know and understand their medical history best.

“The licensure clarity act will now officially recognize and permit the medical care of athletes by their team physicians when the teams travel out of state,” said AOSSM President, Neal S. ElAttrache, MD. “This has been a great advocacy team effort among many of our members, and between multiple societies, including the American Association of Orthopaedic Surgeons, American Medical Society for Sports Medicine and National Athletic Trainers’ Association. There is no doubt that this piece of critical legislation will benefit our athletes and team physicians for years to come.”

Advocacy efforts on behalf of team physicians and sports medicine professionals began in 2015 when several members of the sports medicine community, including AOSSM Past President Allen Anderson, MD and previous AOSSM Council of Delegates Chair, Christopher Kaeding, MD were called by Congress and state legislators, respectively, to address the issue and provide common sense solutions which would allow medical professionals to comply with state licensing rules. This new legislation clarifies how healthcare services and medical liability insurance are provided outside of a professional’s primary state of licensure.

“Previously, the circumstances for treating our athletes during a game or practice in a different state was complicated by a law that didn’t allow for optimal care to be provided. With this legislation, team physicians can now give the same excellent services to their patients no matter their location and without fear of licensure violations and repercussions. This is a big win for the care and treatment of our athletes,” said AOSSM Team Physician Committee Chair, Claude T. Moorman, MD.

The Senate bill (S.808) was introduced in April 2017 by Sens. John Thune (R-SD) and Amy Klobuchar (D-MN). The House version (H.R.302) passed in January 2017 and was introduced by Reps. Brett Guthrie (R-KY) and Cedric Richmond (D-LA)

Published in timesunion 10/05/2018

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