nita limdi labNita Limdi, Ph.D., Pharm.D., professor of NeurologyA quick, precise genetic test can significantly reduce the risk of cardiovascular events by helping to identify more effective medication for some heart patients, according to new findings presented Nov. 15 at the American Heart Association’s Scientific Sessions in New Orleans. Investigators from the University of Alabama at Birmingham collaborated on the multisite study, which was led by researchers at the University of Florida.

Each year, more than 1 million coronary stents are placed in patients with heart disease. After the stent is put in place, patients are prescribed a combination of two anti-platelet medications to reduce the risk of heart attacks or strokes. The most commonly used combination is aspirin and clopidogrel, or Plavix. However, about 25-30 percent of patients have a gene variant that limits or prevents their body’s ability to activate clopidogrel, putting them at a higher risk for major adverse cardiovascular events.

In the new study, UAB investigators joined researchers from seven other institutions to combine data from 1,815 patients. All patients received genetic testing at the time of their stent placement and were followed for one year after the stent procedure.

Thirty percent of patients carried the gene variant that limits or prevents their body’s ability to activate clopidogrel. Based on that genotype, 60 percent of these patients were prescribed alternative anti-platelet medication, which reduced the number of deaths, heart attacks or strokes by nearly half compared with those who continued taking clopidogrel.

“This is the first large U.S.-based collaborative study assessing the implementation of a genetic test in the provision of personalized cardiovascular medicine,” said Nita Limdi, Pharm.D., Ph.D., professor in the UAB Department of Neurology and interim director of the UAB Hugh Kaul Personalized Medicine Institute. “Personalized medicine is about using an individual patient’s information, including genetic data, to tailor treatment.”

“In addition to the current implementation study, research from ongoing clinical trials may help provide additional evidence on effectiveness of genotype-guided therapy,” said Brigitta Brott, M.D., professor in the Division of Cardiovascular Disease in the Department of Medicine.

In addition to identifying the optimal anti-platelet therapy for stent patients, the genetic testing can be done efficiently. Overall, across the nine sites, genetic information was available in about one day. At UAB, the molecular diagnostic laboratory led by Shuko Harada, M.D., associate professor in the Department of Pathology, provided genotype results in 70 minutes, allowing physicians to make changes to the prescriptions immediately.   

“This study demonstrates the power and the promise of genotype-guided therapy in delivery of personalized medicine,” said Limdi. “Genetic testing can be done in real time, guidance on tailoring treatment can be incorporated into the clinical care, and that patient outcomes can be tracked to assess whether genotype-guided therapy improves patient outcomes. Evidence from such studies will collectively inform broader implementation of personalized medicine.”

"Genetic testing can be done in real time, guidance on tailoring treatment can be incorporated into the clinical care, and that patient outcomes can be tracked to assess whether genotype-guided therapy improves patient outcomes. Evidence from such studies will collectively inform broader implementation of personalized medicine.”

The study was conducted through a collaborative genomic medicine network funded by the National Institutes of Health and known as Implementing Genomics in Practice, or IGNITE. Collaborating sites are the University of Florida, Vanderbilt University Medical Center, University of Alabama at Birmingham, University of North Carolina, the University of Maryland-Baltimore, the University of Pittsburgh, the University of Illinois-Chicago, Indiana University-Indianapolis, Sanford Health, Duke University and the University of Pennsylvania.

UAB efforts are supported in part by UAB’s Health Service Foundations’ General Endowment Fund, Hugh Kaul Personalized Medicine Institute, and a grant from the National Heart, Lung, and Blood Institute.

By Bob Shepherd
UAB Media Relations

    UAB and Auburn will team up for a study of magnetic resonance imaging techniques that could enhance epilepsy surgery.  

brain scan verhoefAn MRI image showing the hippocampus of a patient with epilepsy.A $2.6 million, five-year grant from the National Institutes of Health will allow researchers at the University of Alabama at Birmingham and Auburn University to see whether a newly developed magnetic resonance imaging technique will provide more detailed images of the brains of epilepsy patients.

One of the keys to the study will be to see whether the new technique will allow less powerful but more available 3 tesla — or 3T — MRI machines to produce images as clear as the more powerful but fairly rare 7T MRI machines.

“Most MRI machines used for clinical imaging have a field strength of 3T or less,” said Lawrence Ver Hoef, M.D., associate professor in the UAB Division of Epilepsy in the Department of Neurology and principal investigator of the new study. “UAB has several 3T machines, and they are fairly common in hospitals and clinics throughout the state. There is only one 7T machine in Alabama, located at Auburn University, and there are less than 20 in North America.”

The more powerful 7T machines can produce more detailed images, but they are expensive and difficult to use. Due to these limitations, 7T machines are used primarily for research, not clinical care, according to Thomas S. Denney Jr., Ph.D., director of the Auburn University MRI Research Center and a co-investigator.

“The overarching goal is to see whether we can create images on a 3T machine that are as good as or better than we can achieve with a 7T machine, and we anticipate this study will help us verify this new approach,” Denney said.

MRI images are used frequently in epilepsy care. Surgery to remove small sections of the brain responsible for causing seizures is a highly specialized, tailored procedure, and physicians need precise imaging to determine which patients are good candidates for surgery and to minimize unwanted side effects. UAB is the only institution in Alabama that offers epilepsy surgery.

“The hippocampus in particular is a frequent locus for seizures, and it is a most difficult area to image with fine detail,” Ver Hoef said. “There is often a loss of clarity of the internal structures of the hippocampus with traditional MRI. Diagnosis is difficult if not impossible without clear images.”

Previous research done in Ver Hoef’s lab developed a new technique for MRI imaging of the hippocampus referred to as high-resolution, multiple image co-registration and averaging. This technique produces image resolution on a 3T machine that could previously be done only with a 7T machine.

“By altering some parameters and using conventional techniques in an unconventional way, we were able to develop a method for capturing high-resolution images that clearly and consistently visualized the internal architecture of the hippocampus,” he said.

Now, Ver Hoef and his collaborators at Auburn will test the new method by performing MRI imaging on 40 epilepsy patients using the new technique with the 3T MRI machines at UAB and comparing the results to those gained by traditional images from the 7T machine in Auburn.

“If we can show that we can get suitable images from the 3T machines, then we will have a significant improvement in the ability of MRI images to aid in pre-surgical evaluation of these patients,” Denney said. “If it doesn’t work, we reinforce the argument that the field needs more 7T machines for clinical use, which is an expensive proposition.”

 

A second aim of the study will be to see whether changes in the hippocampus could serve as a biomarker for the disease. Using the 3T and 7T machines, the investigators will test two groups of subjects, one with epilepsy well-controlled through medication and one with poorly controlled epilepsy, to see whether differences in the image clarity of the internal architecture are predictive of more severe disease.

 

In collaboration with Farah Lubin, Ph.D., associate professor in the UAB Department of Neurobiology and co-investigator of the new study, a third aim will attempt to see if the investigators can identify an epigenetic biomarker that could help in the future diagnosis of epilepsy. Epigenetics refers to genetic changes not encoded in DNA, but caused by external, environmental factors. Biomarkers are detectable, measurable signs that can be used to diagnose or treat disease.

Ver Hoef says the lack of definition seen in the hippocampus may be the result of astrogliosis, an increase in glial cells called astrocytes, which enlarge and proliferate when nearby neurons die through excitotoxic injury, one of the hallmarks of temporal lobe epilepsy. The researchers will study the brain tissue removed from the hippocampus during epilepsy surgery and compare it to the MRI brain images.

“We anticipate that there will be enhanced astrogliosis in certain layers of the hippocampus in those patients,” Ver Hoef said. “We will collaborate with Dr. Lubin, to measure epigenetic gene regulation and protein levels in the cells within these layers. No one has ever done layer-specific measurements of this type in epilepsy patients before.”

“We will look for correlations between what Dr. Ver Hoef sees on MRI images and what we find in our analysis of brain tissue,” Lubin said. “The hope is that, by employing clinical observation and imaging with laboratory analysis, we will be able to identify and confirm the presence of a biomarker that could provide valuable information for future diagnoses.”

“This is really an exploratory aim of the study,” Ver Hoef said. “Dr. Lubin will try to determine whether there is evidence of epigenetic changes and whether those changes will serve as a biomarker. If we get to a point where we can treat disease by restoring epigenetic balance, this may allow cells to heal themselves, which would be an exciting prospect in the treatment of disease.”

The study is a collaboration of the Alabama Advanced Imaging Consortium, of which Auburn and UAB are founding members. The AAIC promotes collaboration, project management and support between the major research centers in the field of imaging in Alabama.

 
Bob Shepherd
UAB Media Relations           
 
This study, funded by a NEFE grant to University of Alabama at Birmingham, identifies very early declines in financial skills among cognitively normal aging adults through the analysis of a unique federally funded longitudinal dataset. These findings are translated into understandable early warning signs accessible to older adults, their families and a range of professionals.


To see full article, please click the below link:

http://www.nefe.org/what-we-provide/primary-research/early-warning-signs-of-impaired-financial-skills.aspx

This study, funded by a NEFE grant to University of Alabama at Birmingham, identifies very early declines in financial skills among cognitively normal aging adults through the analysis of a unique federally funded longitudinal dataset. These findings are translated into understandable early warning signs accessible to older adults, their families and a range of professionals.

It’s inevitable that an average person will see change in their ability to make financial decision as they age. While there are varying degrees of cognitive decline for each individual, the key is to be prepared for when – not if – this decline occurs. Knowing how to identify early warning signs can help friends, family and caretakers be proactive instead of reactive in the planning process.

The early warning signs of financial decline, all representing a change from the older person’s prior financial functioning, are as follows:

  1. Taking Longer to Complete Financial Tasks
    Examples include preparing bills for mailing; completing checks and check register; and filing income taxes.

  2. Missing Key Details in Financial Documents
    Examples include identifying a bill that is overdue and needs prompt attention; scanning/finding details in complex documents like a bank statement; and completing sections of a check register.

  3. Experiencing Difficulty with Everyday Math
    Examples include determining a return on an investment; calculating a medical deductible; doing two related calculations at the same time, especially making change; and figuring a tip in a restaurant.

  4. Showing Decreased Understanding of Financial Concepts
    Examples include health care concepts like a medical deductible and terms in a bank statement like interest rate and minimum balance.

  5. Identifying Risks in Investment Opportunities
    Examples include identifying a key risk in an investment purchase and emphasizing benefits/return and minimizing risks.

Final Report

Executive Summary

Checklist of Early Warning Signs

Early Warning Signs of Financial Decline (video)



Helping Families Negotiate Aging Parents' Finances (video)



dementia graphic 2016Patients with Alzheimer’s disease or dementia from traumatic brain injury may resist care efforts from family members, such as taking a bath, taking medicine, routine mouth care, abstaining from alcohol or going to a medical appointment.

When this resistance is accompanied by agitation, aggression and irritability, it can trigger distress and health issues among family members, reducing their quality of life and increasing the cost of care for the affected person.

Armed with preliminary evidence that professional caregivers can be taught strategies to alter such behavior, University of Alabama at Birmingham researchers are now launching a three-year study to see if family caregivers can benefit from those same strategies.

The hope is that six weeks of personalized coaching, via phone or online, will reduce the burdens felt by the caregivers of family members with dementia.

“We want to know what the family needs are. How do we meet those family needs?” said David Geldmacher, M.D., professor of the UAB Department of Neurology and director of the Division of Memory Disorders and Behavioral Neurology. “Where do they see gaps? What limits their quality of life?”

The need to help family caregivers of dementia patients is immense. According to the Alzheimer’s Association, more than 5 million Americans are living with Alzheimer’s, and in 2015, more than 15 million caregivers provided an 18.1 billion hours of unpaid care.

Each family will be trained by Rita Jablonski-Jaudon, Ph.D., associate professor in the UAB School of Nursing and a nurse practitioner in UAB Memory Disorders Clinic, and Vicki Winstead, program manager in the School of Nursing.

Caring for a family member

Jablonski-Jaudon has firsthand experience, as a researcher, clinician and daughter-in-law.

“I cared for my mother-in-law, who had early stage dementia,” she said. “We had to move her from her home to ours. After a particularly rough and humbling week, I remarked to a colleague, ‘I am considered a nursing and research expert in dementia; if I’m struggling, how much harder is this for other caregivers?’”

In nursing home research of older adults with dementia, Jablonski-Jaudon and her staff were able to use specific behavioral techniques to minimize care-resistant behavior.

“We were focused on mouth care, the one activity that consistently triggers resistance to care in persons with dementia,” Jablonski-Jaudon said, adding that those techniques were useful to counter a variety of refusal behaviors.

jablonski geldmacherJablonski, GeldmacherIn the current study of family-member caregivers, the UAB team will enroll 50 families of patients with behavioral and psychological symptoms of dementia, and 25 families of patients with traumatic brain injury, or TBI, who have behavioral symptoms that are triggered by caregiver requests. All families will come from patient pools at UAB’s Kirklin Clinic and Spain Rehabilitation Center.

Family members will be able to watch short videos that cover many of the topics and questions Jablonski-Jaudon has encountered in her outpatient clinics. The videos show techniques to prevent and minimize care-resistant behavior, and family-member caregivers will also receive six, once-a-week coaching sessions, via the GoToMeeting computer app. This will enable face-to-face discussion at convenient times for the families, without the need to travel away from home.

A need to help veterans

The UAB study is funded by a $500,000 grant from the U.S. Department of Defense. The Pentagon is interested in dementia for two reasons, Geldmacher says: Surviving World War II and Korean War veterans are growing ever older, and TBI — a risk factor for dementia — is an important type of injury from the Iraq and Afghanistan wars.

Geldmacher says his team will characterize the nature of the problem for each caregiver family. After Jablonski-Jaudon and Winstead finish their coaching, outcomes will be measured by objective data, such as the number of emergency room visits, and self-reported data, using the standard dementia quality of life surveys. There will also be a long-term follow-up at six, 12 and 18 weeks after the coaching.

“So much is based on an individual’s perceived quality of life,” Geldmacher said. “Something that helps one caregiver family might make another family worse. We anticipate that the study will mostly be families where a child takes care of a parent.”

Geldmacher says he used to give dementia patients periodic exams, and he would usually have to tell the family that the patient was getting worse. That routine was jolted when the son of one patient said, “We know she is getting worse. What can we do?”

That challenge changed Geldmacher’s focus. He began to question how well he was treating the family’s quality of life and how he might better help family caregivers.

At UAB, Geldmacher holds the Patsy W. and Charles A. Collat Endowed Professorship in Neuroscience.

“I cared for my mother-in-law, who had early stage dementia… After a particularly rough and humbling week, I remarked to a colleague, ‘I am considered a nursing and research expert in dementia; if I’m struggling, how much harder is this for other caregivers?’”

—Rita Jablonski-Jaudon