For more than 15 years, scientists have known that two types of brain lesions form in patients with Alzheimer’s disease, one type of lesion forming only after the other. David R. Borchelt, a professor of neuroscience, and Guilian Xu, an assistant research scientist at the UF College of Medicine, have used a mouse model to find a potential explanation for how the first type of brain lesion may trigger the second. They report their findings in the current issue of the journal Human Molecular Genetics.

“Understanding how this sequence of events works is thought to be critical and could lead to new therapeutic approaches,” said Borchelt, director of the SantaFe HealthCare Alzheimer’s Disease Research Center at UF and the McKnight Brain Institute.

The lesion that appears first is an amyloid plaque, an incorrectly folded protein structure that forms when a small peptide called the amyloid-beta peptide clumps together. However, scientists have known that amyloid alone does not produce Alzheimer’s disease, and all patients with symptoms have a second type of brain lesion called a neurofibrillary tangle. This second lesion appears later in the disease, and as more of these lesions develop, patient symptoms get worse.

Finding an explanation for the sequential appearance of these lesions has challenged scientists, but understanding how the amyloid plaques trigger the tangles could help scientists devise ways to slow disease progression.

The explanation lies at the heart of how cells function. All cells produce proteins, the molecular workhorses of the cell. Proteins have specific, three-dimensional shapes critical to proper function. This is so important that large amounts of cell energy go into making correctly folded proteins and eliminating incorrectly folded ones. The study by the Borchelt laboratory provides evidence that the abnormal accumulation of the amyloid peptide in the brain that produces the plaque lesions also interferes with brain cells’ ability to keep proteins correctly folded.

“This deficiency in cell function could set the stage for allowing the formation of the neurofibrillary tangles that seem to be the key pathology to symptoms,” Borchelt said.

These tangles form when a protein called tau loses its normal shape and folds into a shape that allows it to bind to other tau proteins. This becomes a runaway process that fills the cell with abnormally shaped tau clumps that produce the tangles.

In recent years, pharmaceutical and biotech companies have begun to look for drugs that could stimulate better protein folding in brain cells. The study by Xu suggests that these companies may be on the right track. Borchelt cautions that more work is needed to fully understand how amyloid pathology is linked to the tangle pathology, but this recent study offers a new avenue of investigation that could lead to a clearer picture.

Funding sources for this work include the National Institutes of Health and the SantaFe HealthCare Alzheimer’s Disease Research Center

GAINESVILLE, Fla. — The University of Florida has launched a free, online tool to help caregivers and family members identify drivers age 65 and older who may be at risk for driving problems.

The Fitness-to-Drive Screening Measure can be completed by caregivers or family members who have been a passenger in a vehicle driven by an older driver within the past three months. After completing the questionnaire, users receive a rating profile of the older driver, recommendations that can be shared with health professionals and links to resources, such as availability of alternative transportation options.

While an on-the-road evaluation, conducted by an occupational therapist who is a certified driving rehabilitation specialist, is ideal for assessing an older adult’s driving ability, it’s not accessible to everyone because of the cost and the limited number of professionals who can administer the test, said Sherrilene Classen, the tool’s lead developer.

“We know from our research and others’ that drivers do not give valid self-reports,” said Classen, an associate professor of occupational therapy at the UF College of Public Health and Health Professions. “Most everybody thinks they are driving better than they actually are. Because we don’t have the evaluators to assess the 36 million older adults who may potentially at some stage require a driving evaluation, we went to the next best step, which is involving their caregivers or family members.”

In studies to determine the accuracy of caregiver and family members’ assessments, UF researchers compared their evaluations of older drivers to professional evaluations of the same older drivers and found that the caregiver and family members’ ratings were consistent and reliable.

The online questionnaire takes about 20 minutes to complete. Four short videos provide step-by-step instructions for each section. Users respond to questions about the older person’s driving history and are asked to rate performance on 54 driving skills, such as staying within lane markings, turning left across multiple lanes when there is no traffic light and merging onto a highway. On the basis of the responses, the screening tool classifies the older driver in one of three categories: accomplished driver, routine driver or at-risk driver.

An “accomplished driver” rating indicates there are no immediate concerns and the driver should consider being screened on an annual basis. Routine drivers may be fit to drive, but there are signs of difficulty with driving in challenging or complex traffic situations. At-risk drivers are advised to stop driving until they speak to a health care provider. A summary report includes specific recommendations that can be printed and shared with a health professional.

“The results give the physician or the occupational therapist a profile from which they can see the driver’s competencies and problem areas,” said Classen, the director of UF’s Institute for Mobility, Activity and Participation. “We hope this tool helps facilitate conversations about driving issues.”

In many cases, older drivers who exhibit difficulties can continue to drive with the assistance of several different interventions. Occupational therapists can offer training on skills like visual scanning of the roadway and can help drivers plan routes to avoid potential hazards. Assistive devices, such as seat pads that raise the driver and improve his or her line of sight, can address physical changes that affect driving. Sometimes a referral to another health provider, such as an ophthalmologist who can diagnose and treat a vision condition, can solve the problem.

“We have a range of options to keep people on the road longer and safer, and in the case of folks who cannot drive or are no longer fit to drive, we are able to provide them with a community mobility plan, including alternative transportation options and travel training, so they stay integrated in their communities,” Classen said.

The UF Fitness-to-Drive Screening Measure can be accessed at fitnesstodrive.phhp.ufl.edu. It is also available on the American Occupational Therapy Association and AAA websites. UF does not collect data from users’ responses and results are anonymous.

Classen and colleagues at AAA have also developed Smart Features for Older Drivers, another free, online resource that offers recommendations for vehicle features that address physical, visual and cognitive changes that affect older drivers. For example, keyless entry and ignition, power mirrors and seats, thick steering wheels and larger dashboard controls are beneficial for drivers with arthritic hands. The guide, which has been recently updated to include current vehicle models, also lists vehicles that have the recommended features. Visit seniordriving.aaa.com/smartfeatures for more information.

“The more I talk to Parkinson’s patients, the more I realized a couple of things,” said Okun, co-director of UF Center for Movement Disorders and Neurorestoration. “Almost nothing is available to patients about basic lifestyle things in any language but English. Even in the most educated patients, who have access to everything, there are still lots of very simple things they aren’t doing. There are lots of things you can do to improve your quality of life.”

To address this need, Okun has authored a book titled “Parkinson’s Treatment: 10 Secrets to a Happier Life.” Published this month, the book is now available on Amazon and Smashwords in more than 20 languages. The e-book retails for $3.99. His goal is to reach every patient and family dealing with the disease.

Globally, about 4 to 6 million people have Parkinson’s disease, and 50,000 to 60,000 new cases are diagnosed in the United States each year, according to the National Parkinson Foundation. As people continue to live longer, the prevalence of Parkinson’s disease in the population also will increase, Okun said.

“It is really important for people to recognize this is a problem,” he said. “If you plan on living a long life, pushing up into the eighth or ninth decade, your chances of facing a disease like this are very high. You cannot escape it.”

But unlike having a disease such as Alzheimer’s, patients can live for decades with Parkinson’s — so understanding how to live well with the disease is crucial.

Some of the topics Okun covers in the book are how to prepare for hospital stays and when to take medications, as well as everyday issues such as sleeping and exercise. Chapters are also devoted to secondary problems such as depression and addiction-like symptoms in Parkinson’s patients.

“Really, these should not be secrets,” Okun said. “If you know these things, you can live a much better life with your disease.”

To Okun, what is perhaps most important is making the information available in languages besides English. The book was made available on both Amazon and Smashwords specifically to increase the number of possible translations. Currently, copies can be found in 20 languages, including English, Italian, German, Portuguese, Spanish, Chinese, Japanese and Arabic among others.

“There isn’t any joking with Dr. Okun about the ‘10 Secrets to a Happier Life’ in Parkinson’s disease,” said Muhammad Ali, who was diagnosed with Parkinson’s in 1984, in a written statement. “This book is a critical resource for Parkinson’s disease patients and families from around the world who speak different languages but suffer from very similar and often disabling symptoms.”

GAINESVILLE, Fla. — Researchers at the University of Florida have performed deep brain stimulation on a patient with Alzheimer’s disease as part of a clinical trial studying whether the treatment can slow progression of the disease.

Called the Advance Study, the multicenter clinical trial will evaluate whether using electrodes to stimulate a part of the brain called the fornix can slow memory decline and improve cognitive function in patients in the early stages of Alzheimer’s disease. The trial is taking place at four sites across the United States, including UF.

“The goal of treating Alzheimer’s disease with neuromodulation is to try to enhance what patients have and slow down memory loss and the process of the disease so they can have a few more years of good function,” said Dr. Michael Okun, co-director of the UF Center for Movement Disorders and Neurorestoration and a site principal investigator for the study. “This is a potentially exciting symptomatic therapy.”

Characterized by memory loss and a steady decline in cognitive abilities, Alzheimer’s disease affects as many as 5.1 million Americans, according to the National Institute on Aging.

Deep brain stimulation is used to treat a variety of conditions, including Parkinson’s disease, dystonia and Tourette syndrome. In the procedure, researchers carefully place electrodes in specific regions of the brain. When these electrodes are turned on, they send electrical signals that prompt a therapeutic response.

“In Alzheimer’s patients there is a very slow loss of brain function,” Okun said. “These slow changes that happen in the brain lead to the clinical symptoms. The idea is that we are going to try and modulate the circuits to see if we can improve some of the symptoms.”

Researchers decided to test deep brain stimulation in the fornix — a part of the brain that connects the hippocampus to the hypothalamus — after the accidental discovery that stimulating that region of the brain provoked vivid memories in patients, Okun said.

The therapy is being tested at four sites: UF, Toronto Western Hospital, the Banner Alzheimer’s Institute and Johns Hopkins University. Overall, 20 patients will be enrolled in the trial, although the electrodes will not be turned on in all the participants, Okun said.

“This is the best way for us to tell if there is a real response versus a placebo response,” he said. “It’s very tricky to measure memory and cognition.”

Aside from testing the effectiveness of the therapy, researchers also are closely examining how stimulating the brain affects the course of Alzheimer’s disease and whether it prompts changes in oxygen, in glucose levels and in blood flow.

“What we have seen so far is there are very interesting changes in blood flow,” Okun said. “It’s very early and it is hard to judge these things just on pictures but the pictures look very interesting. There is definitely something going on in the circuit.”

“Mid and Late Career Issues: An Integrative Perspective” is one of the first works to study the challenges facing workers ages 40 and over. The book, which was released today, is co-authored by Mo Wang, an associate professor of management and co-director of the Human Resource Research Center at the Warrington College of Business Administration.

Synthesizing the limited literature on the topic as well as conducting numerous in-depth interviews with older workers and recent retirees, the authors challenge the stereotypes associated with older workers, such as they are more difficult to train and they lack energy compared with younger colleagues.

“We really found no basis to argue that older workers are harder to train than younger workers,” Wang said. “This stereotype often contributes to employers’ unwillingness for hiring older workers.”

Wang said that when workers reach their early 40s, their career priorities could change. No longer preoccupied with advancement, older workers reassess their position and value.

“When you get to be 40 or 45, your future in your organization becomes clear,” Wang said. “You’re thinking less about climbing the career ladder. You begin to think of other ways to have a legacy.”

Wang said older workers are often better at certain types of work, such as customer service, because they are better equipped to deal with emotional aspects of the job. Experiences such as raising children and caring for elderly parents provide older workers with the skills to deal with emotional obstacles. Such life experience also benefits workers when they change jobs or face layoffs, Wang said.

Wang noted some interesting populations within the older work force that are emerging. For instance, he said, women in their 50s entering the work force are some of the more talented and dedicated workers.

“They love to work,” Wang said. “Their kids are in college and they love the structure work offers them. They’re more mature, they’ve been through a lot and that experience helps them do their job better.”

Wang also cited an increase in older entrepreneurs who use their severance and retirement packages as capital to finance startup ventures.

The book’s co-authors are Deborah A. Olson, an associate professor of management and leadership at the University of La Verne (Calif.), and Kenneth Shultz, a professor of psychology at California State University, San Bernadino.

The new award comes on the heels of $3.9 million in NIH funding that established Florida’s first Pepper Center at UF in 2007.

“We are honored by this strong, continued support as we use scientific tools to tackle the issue of aging,” said principal investigator Dr. Marco Pahor, director of the UF Institute on Aging and chairman of the department of aging and geriatric research in the UF College of Medicine. “Each grant and each resulting research finding brings us one step closer to providing older adults with the means to maintain their health, independence and dignity as they age.”

UF is one of just 15 institutions in the nation to receive the award, which is named for the late Claude D. Pepper, a U.S. senator-turned-representative from Florida. Pepper advocated for the rights of the elderly and championed laws aimed at improving the health and well-being of older Americans.

“The UF Pepper Center has long been interested in maintaining and improving function of older adults in the community,” said Dr. Basil Eldadah, acting chief of the geriatrics branch of the National Institute on Aging. “It has made several significant contributions to our understanding of aging processes, particularly in the areas of prevention and rehabilitation of disability in older people.”

Aging takes its toll in varied ways, affecting many different organs. It can show up as acute effects such as hip fracture or stroke, or as chronic health conditions such as heart disease, osteoarthritis or mental decline. But although aging reveals itself in so many ways, mounting research points to one main process — muscle loss — as having a hand in all those changes.

The work of the UF Pepper Center focuses on understanding age-related muscle loss from different perspectives, and the potential role of skeletal muscle as a key target for therapies to counteract age-related damage to the body. The center’s researchers work in a wide range of scientific disciplines, including molecular biology, gerontology, epidemiology and behavioral sciences.

“The UF Institute on Aging has demonstrated its commitment to easing the burden of age-related illnesses, and has taken a lead role in finding research-based ways to help older adults maintain the best possible quality of life,” said Dr. David S. Guzick, senior vice president for health affairs and president of the UF&Shands Health System. “The Pepper award is a recognition of the world-class, patient-centered research being carried out at UF.”

Since 2007, the center’s researchers have conducted several basic science and clinical studies and published more than 450 scientific papers in noted journals such as Nature, The Journals of Gerontology and the Journal of the American Geriatrics Society.

The researchers have discovered that higher levels of physical activity are associated with longevity, better mood and improved strength among older adults; that low levels of an enzyme found in white blood cells are linked to better survival in frail older adults, and that a cancer drug can extend the lives of older mice, among other findings. Pepper-funded preliminary studies have formed the basis of 36 pending grant proposals totaling $38 million, for larger studies.

In addition to conducting basic, clinical and translational studies of age-related changes in the body, another central part of the center’s mission is to train the next generation of researchers and help them develop skills in both aging research and leadership. Junior faculty selected for the Pepper scholars career development program hail from various disciplines, including medicine, dentistry and public health, as well as from affiliated institutions such as the U.S. Department of Veterans Affairs.

“This invaluable research training complements national efforts to increase the number of physicians and other clinical professionals who are specially trained in the area of geriatrics,” said UF College of Medicine Dean Michael L. Good. “These physicians and scientists will develop tomorrow’s medical tools and therapies that their clinical colleagues will use to care for patients in community practices and health care organizations.”

University of Florida researchers have discovered that people with no signs of dementia during their lives, even though their brains contained the debris typical of Alzheimer’s disease, probably would have experienced health problems had they lived longer, according to a study to appear this week in the open access journal Alzheimer’s Research & Therapy.

Scientists suspect patients who experience relatively few cognitive problems even with a substance called amyloid beta protein accumulating in their brains — the hallmark of Alzheimer’s disease — might collect a less toxic form of the so-called brain plaque.

But UF College of Medicine scientists with colleagues from the http://www.med.ufl.edu/ found few differences when they compared the postmortem brain tissue of Alzheimer’s patients with that from people who accumulated plaque without symptoms, a condition known as pathological aging.

“Pathological aging may be early Alzheimer’s disease rather than a benign form of amyloid protein deposition, or it may be patients with PA are resistant to the toxic effects of the amyloid plaques,” said Dr. Todd Golde, director of the UF’s Center for Translational Research in Neurodegenerative Disease. “It will be important to understand the differences between these two neurodegenerative pathologies in treatment and prevention efforts.”

Alzheimer’s disease is characterized by severe loss of neurons in brain regions important for learning and memory because of overproduction of amyloid beta protein. In a healthy brain, these protein fragments are broken down and eliminated. But when they accumulate, scientists believe amyloid plaque interferes with the brain’s ability to generate new cells and contributes to tangles — twisted masses of protein fibers within the brain cell.

The researchers found similar amounts of insoluble amyloid in Alzheimer’s and pathologically aged brain tissue, with elevated levels in both types of abnormal tissue compared with healthy brain tissue. Researchers also found a great deal of similarity and overlap in the subtypes of amyloid protein, according to Golde, who is also affiliated with UF’s McKnight Brain Institute.

Experimental models suggest that therapies that target these proteins may be effective in preventing or delaying disease development. Without treatment or prevention breakthroughs, a projected 7.7 million patients in the U.S. will have Alzheimer’s by 2030, according to the Alzheimer’s Association. That number will grow to between 11 million and 16 million by 2050.

This is the first accurate estimate of the frequency of the proteins, called autoantibodies, the researchers say. The findings appear online and in an upcoming print edition of the journal Arthritis and Rheumatism.

“This study is a baseline that can help physicians understand, when they identify autoantibodies, how often these proteins indicate disease,” said lead author Edward Chan, a professor of oral biology in the UF College of Dentistry.

The body produces proteins called antibodies to fight against infections, but in some cases, these proteins become turncoats, attacking the body’s own tissues instead. The most common autoantibodies, called antinuclear antibodies, are frequently used as a marker for autoimmune diseases. Although antinuclear antibodies are common, their presence does not always indicate disease.

Chan, and co-lead author Dr. Minoru Satoh, an associate professor of rheumatology and clinical immunology in the UF College of Medicine, along with national colleagues, studied five years’ worth of data from almost 5,000 people, collected through the National Health and Nutritional Examination Survey. The survey amasses a host of health information from adults and children around the country using questionnaires, blood tests and other medical examinations.

No previous researchers have used such a large sample, representative of the general population, to study how frequently autoantibodies occur, Chan said.

The researchers looked for the rogue antibodies in blood serum using an advanced microscope technique that uses a fluorescent dye to selectively light up antinuclear antibodies.

They found that nearly 14 percent of the study population had antinuclear antibodies. The antibodies were more common in African-Americans, women and older adults. The frequency of antinuclear antibodies tends to increase with age then level off over time. And women were more likely to develop antinuclear antibodies as they age.

Unexpectedly, autoantibodies were less common in overweight and obese individuals than in people of normal weight.

“Being obese is often considered a factor contributing to many autoimmune diseases,” Chan said. “So we expected that overweight people might have more autoantibodies. But that is not what we observed.”

Judy Van De Water, a professor of rheumatology and clinical immunology at the University of California, Davis, who was not part of the study, was intrigued that autoantibodies were less common in overweight individuals. She chalks it up to the appetite-reducing hormone leptin — which is produced in fatty tissue and acts as a marker of inflammation. Leptin is often low in people who are obese but high in people who have antibodies that attack the body’s own tissues.

Future studies might look at how exposure to chemicals and other substances in the environment affects the levels of antinuclear antibodies in the immune system, as well as how those levels change over time.

“This is an important study that will serve as the basis for future research on the causes of these antibodies and related diseases,” said the study’s senior author Dr. Fred Miller, acting clinical director of the National Institute of Environmental Health Services, which funded the study. “It’s a first step in the process.”

Now they can live longer thanks to a new minimally invasive treatment that involves inserting an artificial valve that takes over the work of the diseased valve. The University of Florida is among a limited number of facilities around the country initially approved to offer the procedure.

“It’s exciting — this technology opens an option for patients who otherwise do not have a repair option,” said cardiologist Dr. Anthony A. Bavry, an assistant professor in the UF College of Medicine’s department of medicine. “Previously we had to treat these patients with medications, and unfortunately many did not do well. This is a big change.”

The new valve replacement technique, called transcatheter aortic valve replacement, or TAVR, was approved by the U.S. Food and Drug Administration in November 2011. Medical practices approved to perform the procedure had to demonstrate high levels of expertise and collaboration in cardiology and surgery, as well as high-quality facilities for conducting the procedure and collecting data for patient care and monitoring.

Bavry and Dr. R. David Anderson, director of interventional cardiology at UF, will team with thoracic and cardiovascular surgeons Dr. Thomas M. Beaver, and Dr. Charles T. Klodell, to do the procedure at UF&Shands, the University of Florida Academic Health Center. Working in such multidisciplinary teams streamlines and speeds patient evaluation and decisions about the best course of action.

“You have both a surgeon and a cardiologist seeing a patient, reviewing the data and making the best decision about how to treat,” Bavry said.

Among the elderly, severe aortic stenosis is the most common abnormality of the heart valves. But up to one-third of such patients are considered ineligible for surgery. They are instead given medicines to control heart rate and blood pressure, and their heart volume is monitored in order to head off congestive heart failure. Medical treatments ease symptoms but do not prolong life.

In the new TAVR procedure, the artificial valve — framed by a stent and wrapped around a balloon — is transported up to the aortic valve via a large catheter in the leg. The new valve is then anchored into position inside the diseased valve by inflation of the balloon. Placement of the stent is monitored with X-ray and ultrasound imaging.

Patients’ survival chances improve with the new technique. In clinical trials involving 700 patients, treatment with the new procedure cut the death rate nearly in half after one year of having the implanted device, compared with medical therapy alone.

“This is one of the best things that has happened in the last 10 years in interventional cardiology,” said Dr. Samir Kapadia, an interventional cardiologist at the Cleveland Clinic who is one of the leaders in clinical trials of the new technique. “Procedurally, it’s like a miracle — patients are sick, you do the critical part of the valve replacement in 15 to 30 seconds and all of a sudden the heart starts working more efficiently. It has changed the way we do things and has provided treatment options for lots of people who did not have an option before.”

The procedure has also been compared with traditional open surgery in patients who were operable but had a high risk of dying if they did have surgery. After a year, patient outcomes were comparable to those of surgery patients. Additional studies are being carried out to see how the procedure works among patients who are at lower risk of death if they have surgery.

The UF team has begun evaluating patients to see who might be good candidates for the procedure. Tests include chest CT scans, cardiac catheterization and EKGs. They are also reaching out to physicians whose patients might benefit.

Research continues on new ways to insert the valve, as well as on new types of valves, including one that can be repositioned after it has been placed inside the body.

Now, researchers from the University of Florida and elsewhere have identified a new drug that can serve as a “bridge” during that time when patients have to stop taking blood thinners, minimizing both the risk of a heart attack and the risk of excessive bleeding during surgery. The findings appeared Wednesday in the Journal of the American Medical Association.

“This could be a way to satisfy an unmet need and solve a huge clinical problem for millions of patients,” said the study’s lead author, Dr. Dominick Angiolillo, an associate professor of medicine and medical director of the UF Cardiovascular Research Program at the UF College of Medicine-Jacksonville.

Patients who have stents — small mesh tubes that help open up the arteries — must take aspirin or other blood-thinning medication for at least one year after implantation of the devices. But a problem arises if a patient requires open heart surgery during that year.

The patient must stop taking blood thinners five to seven days before surgery to avoid severe bleeding during surgery. But stopping the medication increases heart attack risk. The need for a short-term “bridge” between traditional medication and heart surgery came to national attention when former President Bill Clinton had a mild heart attack in 2004 and needed bypass surgery. Clinton had to wait six days for surgery because he had been taking aspirin and clopidogrel, commercially sold as Plavix.

Angiolillo and colleagues conducted a two-year international clinical trial to determine whether an experimental intravenous blood-thinning drug called cangrelor can keep patients in good health during the presurgery period in which they stop taking traditional oral medication. The trial was funded by The Medicines Company, which manufactures cangrelor.

The researchers determined the appropriate dosage of the drug then administered it to half of the 210 patients in the study. The other half were given a placebo, which did not contain the drug. Neither patients nor physicians knew to which group a patient was assigned until surgery was needed.

The researchers found that cangrelor can effectively thin the blood to keep heart attack risk low without increasing the risk of major bleeding during surgery. Some cases of minor, non-life threatening bleeding occurred among patients on cangrelor. Because the blood-thinning effects of cangrelor are not as long lasting as for traditional medications such as aspirin and clopidogrel, the risk of heavy bleeding is reduced.

“This is a very important scientific first step that really helps us understand what to do with people who are awaiting surgical procedures and are on medications that raise their bleeding risk,” said Dr. Deepak L. Bhatt, an associate professor of medicine at Harvard Medical School, who is not affiliated with the current study but has also conducted research on cangrelor.

Further studies are needed before cangrelor can be used in widespread clinical practice.

The study, sponsored by St. Jude Medical Inc., tested the safety and effectiveness of a constant current DBS device developed by St. Jude Medical to manage the symptoms of Parkinson’s disease. The device aimed to reduce tremors, improve the slowness of movement, decrease the motor disability of the disease and reduce involuntary movements called dyskinesia, which are a common side effect of Parkinson’s drugs.

After treatment, analysis of 136 patient diaries revealed longer periods of effective symptom control — known as “on time” — without involuntary movements. “On time” for patients who received stimulation increased by an average of 4.27 hours compared with an increase of 1.77 hours in the group without stimulation. Patients also noted overall improvements in the quality of their daily activities, mobility, emotional state, social support and physical comfort.

“I think it is safe to say since dopamine treatment emerged in the 1960s, DBS has been the single biggest symptomatic breakthrough for Parkinson patients who have experienced the fluctuations associated with levodopa therapy,” said Dr. Michael S. Okun, first author of the study, administrative director of the UF College of Medicine’s Center for Movement Disorders and Neurorestoration, and the National Medical Director for the National Parkinson Foundation. “This study validates the use of mild electrical currents delivered to specific brain structures in order to improve Parkinson’s disease in select patients with advanced symptoms, and additionally, it explored a new stimulation paradigm. Future improvements in devices and the delivery systems for DBS will hopefully provide exciting new opportunities for Parkinson’s sufferers.”

Only patients who have had Parkinson’s disease for five years or more were included in the study. They were randomly assigned to a control group that delayed the onset of stimulation for three months, or a group whose stimulation began shortly after surgery. All patients were followed for 12 months.

The deep brain stimulation procedure involves surgeons implanting small electrodes into an area of the patient’s brain that controls movement. The electrodes are connected to a device precisely programmed to use mild electrical current to modulate problematic brain signals that result in movement problems.

Today’s voltage-controlled DBS devices deliver pulses of current that vary slightly with surrounding tissue changes. The DBS devices tested in this study are intended to provide more accurate delivery and control of the electrical pulses.

“We are committed to driving research that will provide solutions for physicians and their patients whose needs are currently unmet,” said Rohan Hoare, president of St. Jude Medical Neuromodulation Division. “These results are significant as they offer evidence that stimulation with the Libra constant current system enabled patients to have better motor control and an improvement in their quality of life when compared to the control group.”

The U.S. Food and Drug Administration approved the use of DBS for Parkinson’s disease in 2002. At least 500,000 people in the United States suffer from Parkinson’s with about 50,000 new cases reported annually, according to the National Institute of Neurological Disorders and Stroke. These numbers are expected to increase as the average age of the population rises.

“The study answered some very important questions concerning cognition and mood with lead implantation (alone) versus implantation with stimulation. It also refutes the hypothesis that DBS increases depressive symptoms,” said Dr. Gordon H. Baltuch, a professor of neurosurgery in the Perelman School of Medicine at the University of Pennsylvania and a study author. “The group’s results also showed a decrease in the infection rate to 4 percent from previously published 10 percent. It shows that American neurosurgeons and neurologists with their industry partners are improving the safety of this procedure and working in a collaborative fashion.”

Comparable with other large DBS studies, the most common serious adverse event revealed was infection, which occurred in five patients. Likewise, some participants also reported an increase in the occurrence of slurred speech, known as dysarthria.

“Technology is on the move, and we expect to see continued improvements to DBS approaches, equipment and materials,” said Okun, who is also affiliated with UF’s McKnight Brain Institute. “DBS has set the bar high for the development of new therapies for advanced Parkinson’s disease patients. DBS will be the standard of care gene therapy and other cell-based therapies that are now being conceived will be measured against, and this will hopefully translate into significant improvements in what we can offer our patients.”

In addition to UF and Penn, research was conducted at centers affiliated with Baylor College of Medicine, Columbia University Medical Center, Lahey Clinic, Loma Linda University Medical Center, the Medical College of Wisconsin, Mount Sinai Medical Center, Oakwood Hospital and Health Systems, Texas Health Presbyterian, Rush University Medical Center, the University of Miami, the University of Rochester and the University of Virginia Health Systems.

Writing in the November issue of the Journal of Pain, a multi-institutional team of researchers including scientists with the University of Florida College of Dentistry, revealed the results of the Orofacial Pain Prospective Evaluation and Risk Assessment study, or OPPERA.

One of the largest clinical investigations into the causes of what are technically known as temporomandibular joint disorders, or TMD, researchers hope the discoveries may lead to new methods of diagnosing and treating facial pain conditions, and predicting who will be susceptible to them.

“A major benefit of the OPPERA study is the comprehensive evaluation of demographic, clinical, biological, sensory and psychosocial factors that may contribute to increased risk of TMD,” said Roger Fillingim, a professor of community dentistry and behavioral science at the UF College of Dentistry and the principal investigator for the UF OPPERA site. “It is important to assess variables across these multiple biopsychosocial domains in order to fully reflect the complexity of chronic pain development and persistence.”

Temporomandibular joint disorders, sometimes referred to as TMJ, produce pain that radiates from the jaw and surrounding muscles, restricting jaw movement and causing considerable suffering. Although the disorders vary in duration and severity, for some people the pain becomes a permanent feature of their lives. Estimates suggest more than 10 million people are affected by TMD disorders, according to the National Institute of Dental and Craniofacial Research.

Researchers, led by William Maixner, of the University of North Carolina at Chapel Hill School of Dentistry, followed 3,200 initially pain-free individuals aged 18 to 44 for three to five years, comparing the initially pain-free individuals with 185 people who had long-standing, chronic TMD.

They found chronic TMD becomes more frequent with increasing age in women, but not in men. Early studies indicated women’s greatest risk occurred during early childbearing years and decreased thereafter.

In addition, a wide range of biological and psychological factors appear to contribute to the condition. Compared with pain-free individuals, people with TMD were much more sensitive to mildly painful sensations, they were more aware of body sensations and they experienced greater heart rate increases during mild physical and psychological stress.

Researchers believe the findings provide evidence that chronic TMD is at least partially linked to a person’s perception of and ability to suppress pain, which is determined by the body’s physiological regulatory systems.

Researchers also identified new and important genetic factors that appear to be linked to chronic TMD. Several genes, including some known to influence stress response, psychological well-being and inflammation were identified and may result in new targets for drugs to treat temporomandibular joint disorders and related chronic pain conditions.

The longitudinal study builds on earlier work by members of the multi-university research team, which designed a broad conceptual model to determine the condition’s causes.

“The OPPERA conceptual model proposes that measures of pain sensitivity and psychosocial functioning, both of which are influenced by life experiences as well as genetics, are related to future development of TMD,” Fillingim said. “While the OPPERA conceptual model was developed initially to explain risk for developing TMD, it can be more broadly applied and may help explain the reasons some people develop many different chronic pain conditions.”

The research team will publish additional findings and insights as they continue to analyze the study data.

The National Institute of Dental and Craniofacial Research-funded study was conducted across four study sites, including UF, UNC-Chapel Hill, UF, the University of Maryland at Baltimore, the University of Buffalo and Battelle Memorial Institute.

The initial conceptual model of TMD causation was developed by Maixner, Luda Diachenko, Gary Slade, at UNC-Chapel Hill and Fillingim at UF.

Other study investigators include Eric Bair, and Shad Smith, from UNC; Ronald Dubner, and Joel D. Greenspan, from the University of Maryland; Richard Ohrbach, at the University of Buffalo; and Charles Knott with Battelle Memorial Institute, who served as the director of the Data Coordination Center.

The findings, from a national clinical trial conducted by University of Florida researchers and colleagues, was published online in The New England Journal of Medicine online on Wednesday.

Against expectations, the short-term risk of stroke and related death was twice as high in some cases for patients whose diseased arteries were widened via balloon angioplasty and stent insertion, compared with patients who received medical therapy alone.

Although the 30-day risk of stroke for the stenting patients is concerning, long-term results could be more favorable, the researchers said.

“Five years from now, who will be doing better — the patients who are being medically managed, or those who received a stent?” said study co-author Dr. Michael F. Waters, director of the Shands at UF Stroke Program, who along with Dr. Brian L. Hoh, the William Merz associate professor of neurological surgery in the College of Medicine, led the UF portion of the trial.

The study will have a substantial impact on clinical practice and research, the researchers said, because it is the first randomized stroke trial to pit stenting against nonsurgical treatment for symptomatic intracranial atherosclerosis, a type of stroke caused by artery blockage in the brain. Early results clearly show that intensive medical management is key to improving health, the researchers said.

“This study provides an answer to a longstanding question by physicians — what to do to prevent a devastating second stroke in a high-risk population. Although technological advances have brought intracranial stenting into practice, we have now learned that when tested in a large group this particular device did not lead to a better health outcome,” said Dr. Walter Koroshetz, deputy director of the NIH National Institute of Neurological Disorders and Stroke, which funded the clinical trial.

Every 40 seconds, someone in the U.S. has a stroke. Stroke is the fourth leading cause of death and a leading cause of disability in the U.S. Almost 800,000 people a year have a new or recurring stroke, according to the American Heart Association. With higher than average rates of stroke and related deaths, parts of the southeastern U.S. are together termed the “Stroke Belt.”

Patients with the type of stroke known as symptomatic intracranial atherosclerosis do not respond well to existing treatments. One-quarter of those patients have another stroke within 12 months, and the risk of additional strokes continues in subsequent years. Doctors are unsure what the best course of treatment is.

To find out, the UF researchers and colleagues launched a clinical trial, nicknamed SAMMPRIS, at 50 sites around the country, including at the Medical University of South Carolina, the lead site. The study recruited 451 participants age 30 to 80 who had at least 70 percent narrowing in the arteries in the brain, and had experienced symptoms within the previous 30 days. UF recruited the second-highest number of patients among all sites, through its stroke program, which has been designated a Comprehensive Stroke Center by the Agency for Health Care Administration.

Patients in one group were randomly assigned to receive intensive management involving smoking cessation and medications for blood pressure, cholesterol, diabetes and blood-clot prevention. A second group of patients had that same medical treatment but also had balloon angioplasty and stent implantation into the affected brain artery to improve blood flow.

Almost 15 percent of patients who received stents had a stroke or died within 30 days of enrolling in the study, compared with just under 6 percent of patients in the medical therapy group. The stark difference between the groups persisted almost a year, by which time about 21 percent of patients who had received stents had had negative effects, compared with 12 percent in the medical group.

The researchers initially thought that patients who received stents would have fared better, given the successful use of similar procedures in clinical practice at the Shands at UF Stroke Program and other medical centers.

But the striking difference between the two patient groups prompted the study’s independent safety monitoring body to call off new recruitment. The researchers will, however, continue to monitor previously enrolled patients for the next two years.
It’s not unusual for surgical patients to have more complications at first, the researchers said. That’s because the invasiveness of surgery poses an inherent risk regardless of the illness being treated.

“The real question is, is there a benefit to patients over the long term,” said study co-author and co-principal investigator Hoh, who is an associate professor of radiology and neuroscience in the UF College of Medicine. “If you think about it, when people are concerned about stroke, it’s not just their first month that matters, so we’re waiting to see what the longer-term results will be.”

Over time, improvement of stent design and honing of surgical techniques could help improve outcomes for patients.

“This is certainly not the final say on managing this disease,” Waters said. “This is another piece of the puzzle that helps to guide our hand.”

Previous research has been mostly based on error-prone self-reports of physical activity rather than actual measurements. Now, University of Florida researchers and colleagues have used laboratory-based methods to objectively measure the amount of energy older adults use up as they go about their daily activities, and linked that to cognitive performance.

The researchers found that older adults who expend relatively high amounts of energy in their daily activities are substantially less likely to become cognitively impaired than those who exert less energy. The findings are published in the July 25 issue of the Archives of Internal Medicine.

“There are millions and millions of people who don’t exercise, but we’re beginning to understand that a lot of these people do a lot during the day, and they are likely to accumulate more energy expenditure during the day than others who go out and exercise,” said study co-author Todd Manini, an assistant professor in the department of aging and geriatric research at the University of Florida College of Medicine and the UF Institute on Aging. “These studies are starting to shed light on the fact that accumulating activity during the day can potentially provide health benefits.”

A growing body of research points to the promise of physical activity as a way to prevent or even treat cognitive impairment. But to figure out what types of activities are necessary, and how much, researchers need better estimates of energy spent in various activities.

“That’s going to be a hard question to answer until we can get objective answers about physical activity,” said Kirk Erickson, an assistant professor in the department of psychology and the Center for the Neural Basis of Cognition at the University of Pittsburgh. “If we’re going to translate this research into a clinical setting, we need to provide a quantifiable metric or number for how much physical activity to get.” Erickson was not involved in the current study.

Previous studies have relied heavily on study participants to tell researchers how physically active they were.

“With self-report, we hear what people think they are getting, but it might not be accurate, and doesn’t tell us about energy expenditure the way that objective measures do,” said Erickson, whose imaging studies have shown that one year of participation in modest amounts of exercise can reverse Alzheimer’s-related atrophy in parts of the brain involved in memory formation.

In the new study, the research team, led by scientists at the Heart and Stroke Foundation Centre in Toronto, and at the University of California, San Francisco, moved a step closer to reliably identifying just how much energy people expend.

The researchers studied almost 200 older adults who on average were 75 years old to figure out how much energy people burn during daily activities. First, they calculated the total amount of energy used for the day, then subtracted the basic amount of energy the body needs while at rest.

Participants drank so-called “heavy” water, which has a slight chemical difference from regular water. That allowed researchers to track the body’s consumption of oxygen molecules over time and use that to calculate the number of calories burned.

To find out how much energy a person used while at rest, the researchers used a method called calorimetry to determine the levels of carbon dioxide in the breath.

For comparison, the researchers also collected self-reported activity data.

To assess cognitive function, patients were tested on memory, concentration, orientation, language and other categories.

The more energy spent, the lower the likelihood of cognitive impairment, the researchers found. Patients with the highest levels of activity energy expenditure were 90 percent less likely to become cognitively impaired than those with the lowest levels of expenditure.

The findings are consistent with what other researchers have found, but Manini and colleagues went a step beyond by pointing out the shortcomings associated with using self-reported activity.

Self-reports are highly biased because people might report participating in more activity than they actually do — or they might forget to mention something they did. Self-reports also often focus on sports-like activities and fail to capture movements such as walking around the house or pottering about in the garden.

The link between the onset of cognitive impairment and energy expenditure was stronger when laboratory measurements were used to measure activity than when self-report data was used. In addition, the relationship between the amount of energy spent and the amount of decline experienced was more pronounced for laboratory methods than for self-reports, possibly because of more accurate recording of low-intensity activity.

“The strength of the study was that the researchers didn’t have to just ask people how much physical activity they got — they could actually measure it,” Erickson said.

News stories have long touted resveratrol as a cure for various diseases and a preventative against aging.

”We’re all looking for an anti-aging cure in a pill, but it doesn’t exist. But what does exist shows promise of lessening many of the scourges and infirmities of old age,” said UF exercise psychologist Heather Hausenblas, one of the researchers involved in the study.

A comprehensive review of human clinical research on resveratrol has found it has “anti-aging, anti-carcinogenic, anti-inflammatory and antioxidant properties,” but more research of its benefits is needed, she said.

The study, which appeared online this week in Molecular Nutrition and Food Research, examined results gleaned from thousands of laboratory studies with enzymes, cultured cells and laboratory animals. It was conducted by Hausenblas and fellow researchers James Smoliga of Marywood University and Joseph Baur of the University of Pennsylvania School of Medicine. Their review aimed to examine the current state of knowledge of the effects of resveratrol on humans and to use this information to guide much needed future human clinical trials.

Despite numerous clinical studies on resveratrol’s tonic effects on animals, there is little evidence that it benefits human health. That’s because “there haven’t been many studies on humans,” Hausenblas said.

However, she points out, for years many scientists have thought that a link between resveratrol and human health exists. The French people, for example, enjoy low levels of cardiovascular disease, even though their diets are rich in saturated fats and oils. Some researchers think the reason for this paradox lies in France’s national drink — red wine, which is the most important dietary source of resveratrol. The UF review, said Hausenblas, shows that the resveratrol has considerable potential to improve health and prevent chronic disease in humans. However, further research examining the long-term health effects of resveratrol is much needed.

Exactly how resveratrol works isn’t yet fully understood. Correlating factors such as metabolism, the chemical interplay of molecules, genetics, exercise, age, dosage, and many others all play a role.

Among resveratrol’s most intriguing aspects is how it functions as an antioxidant. Oxidation is a natural chemical process in living tissues that results in a transfer of electrons. When this happens, groups of atoms are formed called “free radicals” that can cause cell damage which in turn provides a pathway for diseases. Antioxidants, however, suppress free radicals. “It’s not so easy to say resveratrol is the main factor,” Hausenblas said. “It’s one piece of the overall puzzle that reduces the free radicals.”

The UF study also reveals that resveratrol’s contribution to good health promises to be widespread. Various clinical trials, for example, indicate that this polyphenol — an antibiotic substance produced by plants as a defense against microorganisms — prevents the growth of some cancers in mice, inhibits enzymes that cause inflammation, shrinks tumors and increases blood flow, thus reducing cardiovascular diseases. In many cases, it also extends the life of obese animals. Some evidence also shows that resveratrol could one day be used to help regulate insulin sensitivity in diabetic patients.

Hausenblas and her colleagues think research that explores resveratrol’s potential to alleviate human infirmities will become increasingly more important as the nation’s 76 million baby boomers undergo the aging process. One trial under way at UF’s College of Medicine in the Institute on Aging examines the effect resveratrol may have on the physical and cognitive skills on older people.