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What is early onset Alzheimer's disease?
Can brain damage be found in retired football players?
Boxing world, and the world at large, react to Muhammad Ali's passing
Fighters need to learn more about concussion risks, study head says
Nevada to require mandatory pre-fight brain testing for boxers and MMA fighters
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UFC donates $1M to Ruvo center for brain trauma study
Ruvo clinic joins global effort to expand drug trials' participation

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Senators Reid And McCain join boxing, MMA Executives to support Professional Fighters Study at Cleveland Clinic Lou Ruvo Center For Brain Health

Bellator MMA, Golden Boy Promotions, Top Rank Boxing and Ultimate Fighting Championship
Leaders Support Study Dedicated to Understanding Effects of Repeated Head Trauma in Fighters

Washington, Feb. 4, 2014: Though fierce competitors in the ring, four professional fighting organizations have put aside their long-standing rivalries to ensure research continues in a landmark study for professional fighters at the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas.

Boxing entities Golden Boy Promotions and Top Rank Boxing and mixed martial arts programs Ultimate Fighting Championship and Viacom's Bellator MMA and GLORY kickboxing have collaboratively committed $600,000 to help continue Cleveland Clinic's Professional Fighters Brain Health Study.

Senators Harry Reid (D-NV) and John McCain (R-AZ) showed their support for the study by joining executives from Cleveland Clinic and the fighting organizations at the announcement. Sen. Reid was an amateur boxer in his youth, and Sen. McCain boxed at the U.S. Naval Academy and has been involved in legislation related to boxing since the mid-1990s. In 2012, the Senators together introduced legislation that created the United States Boxing Commission to oversee boxing matches around the country, administer and enforce federal laws on boxing, and fight conflicts of interest within the sport.

"As a former boxer, I know first-hand the toll that a fighter's body takes when he or she is in the ring," said Sen. Reid. "I want to thank Cleveland Clinic and the leaders of the four fighting organizations for bringing awareness to this important issue facing professional sports today."

The four sporting powerhouses came together to assist in funding the study, which is now in its third year at the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas. The study, which launched in April 2011, is focused on developing methods to detect the earliest and most subtle signs of brain injury in those exposed to head trauma, as well as determining which individuals may be more likely to develop chronic neurological disorders. While it is still in the early stages, researchers are confident the findings will benefit the safety and health of professional fighters. This information could also be applied to other athletes, members of the military and civilians who may experience head trauma.

"I appreciate the fact that top boxing and mixed martial-arts organizations have joined together to directly support the Cleveland Clinic's Professional Fighters Brain Health Study," said Sen. McCain. "The willingness of these organizations to support research into the effects of contact sports on brain health indicates their willingness to take very seriously the welfare of their boxers and fighters and demonstrates that they recognize how crucial fighter safety is to the long-term viability of their sports. I am hopeful that their funding for this study will advance our understanding, diagnosis, and treatment of brain trauma and support similar research efforts going well beyond the ring."

"This gift is significant on many levels, but to see these organizations come together to continue this important work confirms that what we're doing at the center is important to the future of fighting," said Larry Ruvo, Chairman of Keep Memory Alive and Senior Managing Director of Southern Wine & Spirits of Nevada.

To date, the study has enrolled nearly 400 active and retired fighters with the goal of evaluating 625 by its completion. Participation is completely voluntary, and fighters in the study receive free, ongoing assessments of their brain health and brain function, including MRI scans. Individual tests will be repeated annually for at least four years.

"Cleveland Clinic initiated this pioneering study in hopes of answering some key questions about the impact of head trauma, and the professional fighter community has welcomed our effort from the start," said Toby Cosgrove, M.D., President and CEO of Cleveland Clinic. "We're committed to continuing this important research, and it is inspiring to see so many others in our side of the ring."

Studies suggest a percentage of professional fighters have a higher risk of developing long-term conditions such as Alzheimer's disease, Parkinson's disease, chronic traumatic encephalopathy (CTE), depression and other neurological and neuropsychiatric problems, often at a young age. Currently, there is no way to determine if a fighter has sustained cumulative brain damage from head trauma; the Lou Ruvo Center for Brain Health is working toward identifying risk factors in these individuals.

Researchers measure changes in brain volume, nerve fiber injury and connectivity, and blood flow via MRI scans. Any changes seen on the participant's MRI will be correlated with their performance on assessments of cognition, behavior, balance and speech. For fighters who demonstrate a relationship between MRI findings and clinical decline, researchers hope to determine whether there are other factors such as genetics, lifestyle characteristics or the amount or type of exposure to head trauma that make them more susceptible to injury.

Preliminary results from the study have already been published or presented at a number of national meetings. Among the promising findings, the study detected changes in the volume of specific brain regions. The connections between certain areas of the brain were detected by MRI scanning in some individuals within as little as a one-year period, suggesting that MRI measures may turn out to be a useful method of tracking brain changes over time in those exposed to head trauma.

Moreover, the study found that exposure to head trauma – using the Composite Index, a formula that includes number of fights, years of fighting and fights per year – correlates with brain volume and cognitive performance. Those with a higher score on the Composite Index are more likely to score lower on cognitive testing. Pending validation over time, this may be a screening tool to identify fighters at higher risk of brain injury.

"We have made great progress in the study so far, and we are continuing to work toward understanding why certain individuals sustain long-term brain injury from repeated head trauma and how we can detect changes early to protect those individuals," said Charles Bernick, M.D., Associate Medical Director at the Cleveland Clinic Lou Ruvo Center for Brain Health and principle investigator on the study. "With the support of the fighting community, our goal is to use this information to improve safety in these sports for generations to come."

The collaborative gift announced today from the fighting organizations, combined with funds from the Helen and Augustine P. Rapone Research Fund at the Cleveland Clinic Lou Ruvo Center for Brain Health, will provide the necessary support to continue the Professional Fighters Brain Health Study for another year.

For more information on this trial and the Cleveland Clinic Lou Ruvo Center for Brain Health, call 855-LOU-RUVO (1-855-568-7886), visit or email

Cleveland Clinic identifies mechanism involved in alzheimer's-related memory loss

Study uncovers role of Neuroligin-1 (NLGN1) protein.

Sunday, Jan. 19, 2014, Cleveland: Cleveland Clinic researchers have identified a protein in the brain that plays a critical role in the memory loss seen in Alzheimer’s patients, according to a study to be published in the journal Nature Neuroscience and posted online today.

The protein – Neuroligin-1 (NLGN1) – is known to be involved in memory formation; this is the first time it’s been linked to amyloid-associated memory loss.

In Alzheimer’s disease, amyloid beta proteins accumulate in the brains of Alzheimer’s patients and induce inflammation. This inflammation leads to certain gene modifications that interrupt the functioning of synapses in the brain, leading to memory loss.

Using animal models, Cleveland Clinic researchers have discovered that during this neuroinflammatory process, the epigenetic modification of NLGN1 disrupts the synaptic network in the brain, which is responsible for developing and maintaining memories. Destroying this network can lead to the type of memory loss seen in Alzheimer’s patients.

“Alzheimer’s is a challenging disease that researchers have been approaching from all angles,” said Mohamed Naguib, M.D., the Cleveland Clinic physician who lead the study. “This discovery could provide us with a new approach for preventing and treating Alzheimer’s disease.”

Previous studies from this group of researchers have also identified a novel compound called MDA7, which can potentially stop the neuroinflammatory process that leads to the modification of NLGN1. Treatment with the compound restored cognition, memory and synaptic plasticity – a key neurological foundation of learning and memory – in an animal model. Significant preliminary work for the first-in-man study has been completed for MDA7 including in-vitro studies and preliminary clinical toxicology and pharmacokinetic work. The Cleveland Clinic plans to initiate Phase I human studies on the safety of this class of compounds in the near future.

Alzheimer’s disease is an irreversible, fatal brain disease that slowly destroys memory and thinking skills. About 5 million people in the United States have Alzheimer’s disease. With the aging of the population, and without successful treatment, there will be 16 million Americans and 106 million people worldwide with Alzheimer’s by 2050, according to the 2011 Alzheimer’s Disease Facts and Figures report from the Alzheimer’s Association.

Cleveland Clinic participates in largest nationwide alzheimer's disease prevention trial

Two sites to test diabetes drug's effectiveness in prevention alzheimer's disease in high-risk individuals.

Wednesday, January 8, 2014, Las Vegas: Researchers at Cleveland Clinic are participating in a new clinical trial designed to test the effectiveness of using a currently-approved diabetes drug to prevent the development of Alzheimer’s Disease in people who are predisposed to develop the condition. The study will also look at whether a new genetic biomarker, TOMM40, is an additional indication of a patient’s elevated risk of developing the disease.

The TOMMORROW trial, a Phase 3, five-year, double-blind, placebo-controlled study, is the nation’s largest prevention clinical trial for Alzheimer’s disease. The trial examines if the drug pioglitazone (AD-4833), currently FDA approved to treat type 2 diabetes, reduces inflammation and has a protective effect in the brain that can prevent high risk-patients from developing mild cognitive disorder and Alzheimer’s disease. The link between type 2 diabetes and Alzheimer's may occur as a result of the complex ways that type 2 diabetes affects the ability of the brain and other body tissues to use sugar (glucose) and respond to insulin.

“The TOMMORROW trial allows us to take a look at how we can combat Alzheimer’s disease before it even takes hold by studying cognitively normal individuals with no symptoms of memory impairment,” said Jeffrey Cummings, MD, Medical Director at Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas. “Until now, the bulk of our research was focused on treating the disease, but with the advances in the science behind genetic biomarkers, we can now identify those who are predisposed to Alzheimer’s and start down the path of identifying drugs that may have the potential to prevent the disease all together.”

AD-4833 regulates glucose metabolism and insulin sensitivity, reduces inflammation and has a protective effect in the brain that could prevent high-risk individuals from developing Alzheimer’s disease. This study will evaluate AD-4833’s efficacy versus placebo in delaying the onset of Alzheimer’s in cognitively normal individuals, comparing the areas of cognitive decline, functional decline and daily living activities.

Researchers at Cleveland Clinic Florida in Weston, Fla. and the Lou Ruvo Center for Brain Health in Las Vegas, Nev. will screen thousands of people with the goal of enrolling about 120 participants per site. Those selected to participate will be randomized into either an active treatment or placebo group and will take the treatment drug orally once per day. Approximately 5,800 people will participate in TOMMORROW worldwide.

Participants must be cognitively normal, exhibiting no symptoms of memory impairment, and between 65-83 years old. All participants must undergo a genetic blood test, which will determine if the individual has a higher or lower possible genetic risk to develop Alzheimer’s disease. The genetic blood test is composed of APOE and TOMM40 genotypes and the individual’s age. Previous studies have shown age and APOE indicate an elevated risk of Alzheimer’s disease, and TOMM40 is hypothesized to further refine the risk determination.

High-risk participants will have a 50 percent chance to receive either AD-4833 or the placebo, and low risk participants will either receive the placebo, or in some cases, may not be eligible for the study. After randomization into the study, participants will be contacted every three months. Phone calls will be conducted at three and nine months, and site visits will be conducted at six and 12 months.

“The screening process to find the participants in the TOMMORROW study is extremely important. We’ll be identifying a unique group of individuals who have not yet been affected, but have a real possibility of a future with Alzheimer’s disease,” said Gabriel Léger, MD, principal investigator of TOMMORROW at Cleveland Clinic Lou Ruvo Center for Brain Health.

This trial is an example of a repositioning project, where researchers take an approved drug and study it in a new use or condition. Repositioning studies are designed to accelerate the drug development process and reduce the need to constantly invent new drugs when current treatments could be used in new ways.

The TOMMORROW study was initiated and funded by Takeda Pharmaceutical Company Limited (Takeda) and its partner, Zinfandel Pharmaceuticals Inc.

For more information on this trial and Cleveland Clinic Lou Ruvo Center for Brain Health, call 855-LOU-RUVO (1-855-568-7886), visit or email

Cleveland Clinic teams with NFL players association to assess, improve brain health, well-being of retired players

Wednesday, Nov. 13, 2013, Cleveland: As the long-term effects of sports-related collisions and brain trauma continue to cause concern, Cleveland Clinic is teaming with the National Football League Players Association (NFLPA) to assess and improve the brain health and overall well-being of retired professional football players.

The NFLPA program, called The Trust, will offer physical and neurological evaluations to former players, followed by a comprehensive plan to relieve symptoms, restore function, improve cognitive skills, and slow neurodegeneration for those who have sustained recurrent head trauma.

Cleveland Clinic will host players at three sites – at its main campus in Cleveland, Ohio; at Cleveland Clinic Florida in Weston, Fla.; and at the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas. Players can also choose to visit the University of North Carolina in Chapel Hill, N.C. or Tulane University in New Orleans.

“Athletic injuries and sports-related brain trauma have become part of the public consciousness and are being viewed as legitimate public health problems,” said Jay Alberts, Ph.D., director of the Cleveland Clinic Concussion Center. “Former professional football players, in particular, are at increased risk for neurological disease. The goal of this program is to identify potential problems – physical, neurological or cognitive – earlier, which may lead to earlier interventions and treatments.”

Players who choose to take part in the program will begin with a comprehensive medical history and exam that will include the player’s injury history, functional symptoms and personal concerns. The program will include a brain scan with a functional MRI, cognitive evaluations, psychological interviews, and balance assessments, in addition to cardiovascular evaluations, a prostate screening, nutrition counseling, and life skills consultation.

“The cumulative effect of repeated collisions and brain trauma are now recognized as major factors in declining health – both mental and physical – among retired athletes who participated in contact sports,” said Charles Bernick, M.D., associate medical director at the Cleveland Clinic Lou Ruvo Center for Brain Health. “These injuries can have lifelong ramifications, manifesting as cognitive impairment, decreased motor functioning, incessant pain, and psychological/behavioral issues, such as irritability, impaired insight and impulse control, paranoia, violent outbursts, and even suicide. By taking a proactive approach, this program is helping retired players be assessed, diagnosed and treated before symptoms arise.”

After their visits, players will be given personalized short-term and long-term treatment plans customized to meet their specific needs. The plan will include ongoing communication between the player and his healthcare team, whether by telephone, computer, video conferencing or letters, based on the patient’s preference.

“If problems arise, we can bring the players in before the issues become too serious,” Alberts said. “Each player will leave here with their own neurological passport that outlines exactly where they are cognitively and neurologically. If changes occur after they go home, we can intervene in a systematic and strategic way.”

In addition to The Trust, Cleveland Clinic has been at the forefront of concussion treatment and research, developing the Cleveland Clinic Concussion Assessment System (C3), an tablet-based app that offers a global assessment of concussion symptoms; designing an intelligent mouthguard and a blood test to assess concussions; studying designs for better youth football helmets in association with NFL charities; and working with the Nevada Athletic Commission on a landmark study with professional fighters to determine whether MRIs of the brain can detect subtle changes that correlate with impaired thinking and functioning.

The Cleveland Clinic Concussion Center offers concussion evaluations and management through a collaborative team effort made up of primary care sports medicine physicians, neurologists, neurosurgeons, neuropsychologists, certified athletic trainers, vestibular therapists, radiologists, neuro-ophthalmologists, and researchers, all dedicated to patient recovery. NFLPA members interested in more information from Cleveland Clinic can call 216-445-9815.

NFLPA members can learn more about The Trust at or by calling (202) 212-6180 or 1-866-725-0063.

Cleveland Clinic Launches First In Human Trial To Test Cancer Drug's Effects On Reversing Alzheimer's Disease

Lou Ruvo Center for Brain Health Studying Bexarotene on the Heels of Recent Study Showing Significant Reduction in Amyloid Levels in Mice

2013, Las Vegas: Researchers at the Cleveland Clinic Lou Ruvo Center for Brain Health have begun a landmark Phase IIa clinical trial to determine if bexarotene (Targretin™), a drug currently FDA approved to treat skin cancer, can remove a protein build-up in the brains of Alzheimer’s patients, as it did in a recent animal study.

Known as the BExarotene Anti-amyloid Therapy for Alzheimer’s Disease (BEAT-AD) study, this is the first human trial in the world of bexarotene to treat Alzheimer’s disease. It is an investigator-initiated, proof-of-concept study led by Dr. Jeffrey Cummings, Director of the Cleveland Clinic Lou Ruvo Center for Brain Health, and Dr. Kate Zhong, Senior Director of Clinical Research Development at the Cleveland Clinic Lou Ruvo Center for Brain Health.

Alzheimer’s disease is a complex brain disease in which the first recognizable abnormality is the accumulation of a protein in the brain called “amyloid,” which is normally cleared from the brain in healthy individuals. Many of the treatment approaches currently being studied in clinical trials are aimed at reducing the production or increasing the removal of this protein. Oral medications and vaccines are also being developed to try to control this protein, but no drug has yet proven to be effective against the amyloid protein.

According to a recent study published in the journal Science, mice genetically engineered to produce the amyloid protein showed a substantial reduction in amyloid levels in the brain within days of using bexarotene. The dramatic reduction was accompanied by improved performance on several measures of cognition and behavior.

“We were encouraged by this remarkable effect and realized that, because it was FDA approved, we could test it with Alzheimer’s patients immediately,” said Dr. Cummings, who is a paid consultant for Eisai Pharmaceuticals, the manufacturer of bexarotene. “If it works the same way in humans as it did in Mice, it will be a wake-up call to all of us in the Alzheimer’s research community that this drug and its unique mechanism for removing amyloid needs to be explored more closely.”

Because bexarotene is approved for skin lymphoma in humans, the dosing, side effects and methods of manufacture are already known. Additionally, this type of cancer occurs most commonly in the elderly population, so the drug has already been tested and found to be safe in an older patient group. The drug has known side effects as many cancer drugs do, all of which are being carefully monitored in the study.

BEAT-AD is a double-blind, placebo-controlled study being conducted at the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas. A total of 20 patients with mild to moderate Alzheimer’s disease will participate in the eight-week study. Patients will be randomized into either an active treatment or placebo group and will take the treatment drug orally two times per day. The protocol was designed to allow for everyone who participates in the trial to eventually be treated with the drug. Some will have two months of treatment while some will have one month, depending on which group they are randomized to at the outset.

The trial comes at an important time in Alzheimer’s research, now that a new diagnostic agent called florbetapir (Amyvid™) is FDA approved for use during Positron Emission Tomography (PET) imaging of the brain to measure the level of amyloid plaques.

“With this biomarker, we are able to determine the effect of bexarotene on our primary outcome, amyloid in the brain of Alzheimer’s patients, in an objective, precise way,” said Dr. Zhong.

Participants will have multiple clinical and neuropsychological evaluations, blood tests, and brain scans throughout the two-month study, including a florbetapir PET scan at the screening visit, at the four-week mark and at the conclusion of the study (eight weeks). Participants will have their amyloid blood levels measured during the study to see signs of the protein exiting the brain. A team in the behavioral neuroscience lab led by Dr. Jefferson Kinney at University of Nevada at Las Vegas (UNLV) will conduct these tests. UNLV will also be providing genotype analysis for all participants as a way to integrate genetic medicine into drug discoveries. The research team will be looking at whether patients with various kinds of apolipoprotein E (APOE) gene have different responses to bexarotene.

In addition to conducting the study, Cleveland Clinic Lou Ruvo Center for Brain Health designed the protocol and lined up all of the collaborators necessary to perform the array of services and expertise essential to this landmark study. Several philanthropists also stepped up to help fund the trial. The Center has grown to be one of the leading centers for conducting clinical trials in neurodegenerative disorders in the world.

“We put all of our best science and planning into this experiment because it is very, very important research that needs to be done,” said Dr. Cummings. “This study is funded exclusively by philanthropy, which is inspiring to me and shows the true impact that donors can have on advancing research. In addition to their generosity, this trial requires patients and their caregivers to give their time to participate. It illustrates the essential role of patients in advancing the science in Alzheimer’s disease.”

In addition to the amyloid findings, this study will shed important light on the relevance of mice to humans when it comes to Alzheimer’s research. Currently, mice are used as the screens for all Alzheimer’s drugs, but researchers do not have a clear sense of their predictive value in humans.

Also, if amyloid levels increase in the blood while also decreasing in the brain, these findings will tell researchers how the drug works to transport amyloid across the blood-brain barrier, which could be helpful not only in Alzheimer’s research but in many other areas of neurological research. Being able to permeate the blood-brain barrier is a common challenge in brain drug development.

“We know that bexarotene removes amyloid from the brain by transporting it across the blood-brain barrier, which is an unusual means that hasn’t been studied much,” said Dr. Cummings. “If the trial tells us how this works, then we can develop drugs that use the same mechanism but are less toxic than a cancer drug.”

This trial is an example of a repositioning project, where researchers take an approved drug and study it in a new use or condition. Repositioning studies are designed to accelerate the drug development process and reduce the need to constantly invent new drugs when current treatments could be used in new ways. The Center plans to look at repositioning other drugs to test them in patients with neurocognitive disorders in the near future.

For more information on this trial and the Cleveland Clinic Lou Ruvo Center for Brain Health, call 702-685-7073, visit or email

Keep Memory Alive Expands Fine Art Program
Offers Works Available For Purchase

Revamped Collection Focuses on Local Artists, with Proceeds Benefiting Keep Memory Alive and Cleveland Clinic Lou Ruvo Center for Brain Health

Tuesday, May 29, 2012, Las Vegas: Keep Memory Alive is re-launching its Fine Art Program at Cleveland Clinic Lou Ruvo Center for Brain Health by expanding the number of works on view and continuing to make much of the collection available for purchase. Proceeds from each sale benefit both Keep Memory Alive and the artist. Keep Memory Alive’s mission is to raise awareness and funds in support of Cleveland Clinic Lou Ruvo Center for Brain Health.

The size of the collection at Cleveland Clinic Lou Ruvo Center for Brain Health has increased from 39 to 59 pieces, 75 percent of which are new works. The newly added pieces reflect an effort to support local and regional artists, in addition to the works already on view from internationally recognized artists. Michele Quinn, curatorial advisor of the Keep Memory Alive Fine Art Program, wanted to both expand the collection and go more in-depth with each of the artists on view.

“With our growth, we now have between two and three pieces from each artist creating a comprehensive collection that is more reflective of the local aesthetic,” Quinn said. “We’re thrilled to have a program that supports both the local arts community and Cleveland Clinic. The mission of Keep Memory Alive is something many of the featured artists have gravitated toward, and the ability to have their work displayed in a Frank Gehry building is an exciting opportunity.”

Works on view throughout the building are available for purchase. Artists have been selected based on individual merit and work that best represents the spirit of the architecture of the Frank Gehry-designed facility.

The re-opening of the collection coincides with the launch of a new website, Lou Ruvo Center of Art, dedicated to showcasing each piece, providing information on the artists and a calendar of upcoming events. For information about purchasing the artworks on view or to schedule a tour of the Keep Memory Alive Fine Art Program at Cleveland Clinic Lou Ruvo Center for Brain Health, email or call (702) 263-9797.

“This type of philanthropic program is unique for a healthcare organization and our perspective has always been that a focus on art in a medical environment can enliven and inspire our patients and employees,” Quinn said. “Through the new website and offering of tours we hope to increase community access to this exciting collection of artists. There is a lot of energy happening in downtown Las Vegas and Symphony Park, and we hope this can contribute to this movement.”

A subsidiary of Cleveland Clinic, the Keep Memory Alive Fine Art Program has been designed to support and bring awareness to the effects of cognitive disorders, the brain and its aging process. The Cleveland Clinic Art Program was established by the Arts & Medicine Institute at Cleveland Clinic in 2006. The program’s mission is to enrich, inspire and enliven patients, visitors, employees and the community. Learn more from Cleveland Clinic's Arts & Medicine Institute.

The Lou Ruvo Center for Brain Health is involved in numerous research projects dedicated to the treatment, diagnosis and cure for memory, movement and cognitive disorders.

Watch these videos to learn more about the recent projects and innovations.

Use the scroll bar on the right to see the full menu of videos. Click on the video listed to play the video.