Tag Archives: Biostatistics and Epidemiology

Study looks at whether daily limb compressions reduce dementia

A new study is looking at whether short, daily bouts of reduced blood flow to an arm or leg can reduce the ravages of dementia.

It’s called remote conditioning, and researchers say it activates natural protective mechanisms in the brain that should help about half of dementia patients.

The approach uses a blood pressure cuff-like device to temporarily restrict blood flow to an appendage repeatedly for a few minutes each day, which increases blood flow to other body areas, including the brain, said Dr. David Hess, Chairman of the Department of Neurology at the Medical College of Georgia at Georgia Regents University.

Increased flow activates endothelial cells lining blood vessels, calling to action a series of natural protective mechanisms that can be effective wherever blood travels, Hess said. Interestingly, the mechanisms seem most active in areas of impaired flow, such as those deep inside the brain, where most dementia has its roots.

“The most powerful way to protect the brain is to cut off blood flow to it for a short period of time to condition it,” said Hess. “What it does is elicit these protective pathways so when potentially lethal ischemia comes, you can survive it.” What it also appears to do is help permanently improve blood flow to these deep regions of the brain.

Age and being a female are two of the major risk factors for dementia. With nearly 15 percent of the U.S. population age 65 and older and half being female, Hess calls dementia a major health concern. “This is a big epidemic coming. This is a big killer and disabler, and everybody is concerned about this.”

A two-year, $750,000 translational grant from the National Institute of Neurological Disorders and Stroke should help Hess and his research team do the additional animal studies needed to move this safe and inexpensive technique for dementia to human studies.

“We think reduced cerebral blood flow, particularly in the deep white matter, is a major trigger of dementia,” Hess said. The white matter is primarily composed of axons, which connect neurons and different areas of the brain to each other and enable the brain to communicate with the body. The white protective coating on the axon is why this deep brain area is called white matter.

Hess, who is also a stroke specialist, says this area is particularly vulnerable to ischemia because the blood vessels that feed it are small and have long, tortuous routes. Strokes and/or impaired blood flow can lead to classic dementia symptoms such as forgetfulness and an unsteady gait.

By age 70, essentially everyone has some white matter disease, but in some it can be devastating. “You cannot go out in a car and find where you are going. You may not even be able to find your car. You can’t cook meals without setting the house on fire,” Hess said.

“What we want to do long term is find people who are at risk for dementia – they already have some white matter damage you can see on an MRI – then we condition them chronically with this device in their home,” Hess said. Chronically is a key word because, as with exercise, when this conditioning stops, so do its benefits. In fact, this passive therapy provides blood vessels many of the same benefits as exercise. “If you can exercise, you probably don’t need this,” Hess adds.

Previous studies in their animal model of vascular dementia have shown that just two weeks of daily, short bouts of ischemia to an appendage can improve the health of the important white matter. The new grant is allowing them to use a similar approach for periods of one and four months in older mice of both genders to better understand the mechanisms of action and how long and how often therapy is needed. While they don’t make as much as human, mice do make more amyloid, a protein that deposits in the brains of patients with Alzheimer’s, when brain blood flow is impaired. Mice make less with the conditioning, so the researchers also are looking further at that result.

A small intramural grant is enabling similar studies with a pig model in collaboration with University of Georgia colleagues Dr. Simon R. Platt, professor of neurology and neurosurgery in the College of Veterinary Medicine, and Dr. Franklin D. West, assistant professor in the College of Agricultural and Environmental Sciences.

While he notes that multiple natural mechanisms are activated, Hess and his team are focusing on how the temporary bouts of increased blood flow prompt endothelial cells to make the precursor for the blood vessel dilator nitric oxide.

“The enzyme that makes nitric oxide is upregulated and stimulated quickly,” Hess said. Nitric oxide gas has a short life, but when a lot is dumped in the blood, it’s oxidized into nitrite – the same stuff put in hot dogs – which circulates throughout the bloodstream so it goes wherever blood goes. Although just how this happens is unclear, when the nitrite gets to an area of low blood flow, it is converted back to nitric oxide, which helps improve flow, Hess said.

The MCG researchers are applying for federal funding to do trials in humans who are at high risk for stroke because of small vessel disease deep in the brain. In 2012, they published results of a small study in the journal Stroke indicating that successive, vigorous bouts of leg compressions following a stroke trigger natural protective mechanisms that reduce damage and double the effectiveness of the clot buster tPA. Similar studies have been done by others in patients with heart disease.

Vascular dementia is considered the second most common cause of dementia after Alzheimer’s disease, according to the Alzheimer’s Association. There are currently no drugs approved by the U.S. Food and Drug Administration specifically for vascular dementia.

Collaborators at MCG and GRU include Dr. Mohammad B. Khan, postdoctoral fellow in Dr. Hess’ lab; Dr. Nasrul Hoda, College of Allied Health Sciences; Dr. Philip Wang, Department of Psychiatry and Health Behavior; Dr. Ali Syed Arbab, Department of Biochemistry and Molecular Biology; Dr. Nathan Eugene Yanasak, Department of Radiology and Imaging;  and Dr. Jennifer Waller, Department of Biostatistics and Epidemiology.

Biostatistics and Epidemiology Seminar Series

The Department of Biostatistics & Epidemiology at Georgia Regents University cordially invites you to attend a seminar, presented by Stephanie A. Norman, DVM, MS, PhD., with Marine-Med: Marine Research, Epidemiology, and Veterinary Medicine, Seattle, WA.

The title of the presentation is “Becoming Friends with Your Veterinary Epidemiologist: What Can They Tell You about Animal, Environmental and Public Health?”. Visit our departmental website at http://biostat.gru.edu/seminars.htm

This seminar will be held in AE 1002 (Biostatistics Seminar Room – Pavilion I) beginning at 10 a.m., Feb. 13. Refreshments will be served at 9:30 a.m.

Chen elected Fellow of the American Statistical Society

Dr. Jie Chen
Dr. Jie Chen

AUGUSTA, Ga. – Dr. Jie Chen, Professor in the Department of Biostatistics and Epidemiology at the Medical College of Georgia at Georgia Regents University, has been elected a Fellow of the American Statistical Society.

Chen was among 63 new Fellows from 25 states, the District of Columbia, and seven countries honored for their professional contributions and leadership in the field of statistical science at the recent Joint Statistical Meetings in Boston. The new MCG faculty member was honored for her contributions to change point problems and their applications to genomic data, for high-impact collaborative biological research, for excellence in student mentoring, and collaborative clinical research in neurology and oncology.

The American Statistical Association is the world’s largest community of statisticians whose members work in industry, government, and academia in more than 90 countries.

Chen, who came to MCG in August from the University of Missouri-Kansas City where she was Chairwoman of the Department of Mathematics and Statistics, is a member of the ASA’s Caucus of Academic Representatives. She is Associate Editor of the journals Frontiers in Bioinformatics and Computational Biology and Journal of Probability and Statistical Science.

She specializes in statistical change point analysis, which has a wide variety of applications in industrial quality management, climatology, economics and finance, medicine, and genetics. She co-authored the research monograph “Parametric Statistical Change Point Analysis,” published by Birkhäuser in 2000 as well as a second edition in 2012. Her expertise also includes applied statistics, statistical inference, statistics in bioinformatics, biostatistics, and statistical modeling of genomics data.

Biostatistics: A vital and growing program

The Department of Biostatistics and Epidemiology at Georgia Regents University not only offers degree tracks in the growing field of medical research, but also offers key collaborative support for most medical research conducted on the Health Sciences Campus.

Biostatistics, in layman’s terms, is the use of statistics in biological and medical research, and the department helps many groups on campus with a variety of issues related to design, analyses, and interpretation of biological and medical data.

“The overarching mission of our department is to advance knowledge in the fields of biostatistics and epidemiology and to provide leadership and scholarship in research, teaching, and mentoring for the advancement of biomedical science and the improvement of human health,” said Dr. Varghese George, Chairman of the department. “The mission is achieved by (1) implementing high-caliber teaching programs for graduate students and others, (2) collaborating with investigators in biomedical and public health research, and (3) conducting original research to develop and evaluate biostatistical and epidemiologic methodologies.”

The department has 13 faculty members. The degree tracks offered by the department include master’s and doctorate degrees in biostatistics, and master’s and certificate programs in clinical and translational science for young faculty, fellows, and residents.

“In addition, we also teach a variety of courses for many training programs on the Health Sciences Campus, from nursing students, medical students and to allied health students,” said George. These courses teach students how to design research studies, how to collect and analyze the data, and how to interpret the results within the given scientific context.

“Demand for professional opportunities in biostatistics is very good, and constantly growing. Our graduates have had no problems finding great jobs,” he said. “Insurance companies, pharmaceutical industries, banks, and of course, hospitals and universities are all looking for well-trained biostatisticians.”

The department is also working with the Department of Mathematics on Summerville campus on a joint undergraduate/graduate program to help meet the growing demand for biostatisticians. Through this program, entering freshman would spend three years in the Mathematics Department and an additional two years in the Biostatistics Department.  Within five years, the student would have a bachelor’s degree in mathematics and master’s degree in biostatistics. The program affords students the opportunity to avoid course duplications, and focuses on courses most relevant to the dual degrees.

“We are really excited about the program, and we are jointly working out the final details,” George said. “We hope to be able to offer it in fall of 2014.”

The second goal of the department is to help researchers with their clinical and basic science research. Often a researcher is an expert in a specific scientific field, but not necessarily an expert in statistics, and that is where the Biostatistics Department can help.

“We participate in studies that have thousands of participants with large volume of data on each participant, and we help researchers analyze the data to find the pertinent pieces of information that they are looking for,” George said. “We help them design the study, test the relevant research hypotheses, help collect data, clean up the data, and perform the correct statistical analyses. We collaborate with almost all researchers on the Health Sciences Campus with their statistical needs. Now, we hope to expand our research collaborations to the Summerville campus.”

The department also works with off-campus organizations through GRU’s Biostatistics Consulting and Survey Center. “We just finished a rather large project for the Department of Defense,” George said. “We also have been conducting the biannual salary survey of non-academic statisticians for the American Statistical Association.”

Our faculty also pursues methodological research, developing new statistical methods and evaluating methods developed by others, to meet the analytical needs of today.

“When I first began my career in statistics, studies were generally very small. The numbers we were using were small, in the order of tens and hundreds,” George said. “But now with faster and cheaper computers, researchers can collect data in the order of millions and billions. “The numbers are staggering on their own, and we have to find better ways to organize and analyze these numbers to reach meaningful conclusions,” he added. “It can get really intense, and we are always working to find better ways to get better results.”

In the end, that’s what the Biostatistics Department is about — developing and implementing the best analytical tools to do scientific research accurately, efficiently, and in the most ethical manner, for the purpose of improving human health.

Department of Biostatistics & Epidemiology Seminar Series

The Department of Biostatistics & Epidemiology cordially invites you to attend a seminar on Thursday, April 4 at 1 p.m. in the Greenblatt Library. The guest speaker will be Courtney E. McCracken,Department of Biostatistics & Epidemiology, who will present Correlation Coefficient Inference for Left-Censored Biomarker Data with Known Detection Limits.

For more information, visit http://www.biostat.gru.edu/seminars.htm