GRECC Research News: October - December 2017 - Geriatric Research Education and Clinical Center (GRECC)
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GRECC Research News: October - December 2017

Antipsychotic Use in Parkinson’s Disease Patients (Ann Arbor GRECC)

Use of antipsychotics (APs) in Parkinson’s disease (PD) is common. Noting the high rate at which persons with PD experience psychosis and dementia. Investigators at the Ann Arbor GRECC hypothesized that use of APs placed patients at elevated risk for mortality. Multivariate analysis of a Veterans Health Administration database of PD patients revealed that antipsychotic users had more than twice the risk of death as observed in a matched group of non-users. The commonly used atypical antipsychotics identified during the study were olanzapine, risperidone, and quetiapine. This work highlights the need for caution when prescribing atypical antipsychotics to PD patients and the importance of always considering non-pharmacologic strategies in managing psychosis.

To learn more about this research, contact Dr. Helen C. Kales.

Celebrating 30 Years! (San Antonio GRECC)

The San Antonio GRECC celebrated 30 years of research in aging, educating the next generation of geriatric providers, and developing and disseminating innovative models of care for older adults.

Recently, the SA GRECC organized a number of activities to acknowledge the special anniversary. To kick off the celebration, SA GRECC leaders recognized faculty and staff for their integrity, commitment, advocacy, respect and excellence. The ceremony included a special recognition for employees with 25 and 10 years of service. SA GRECC also hosted an ice cream social in which South Texas Veterans Health Care System (STVHCS) employees got the scoop about the GRECC’s mission, goals, projects, and services. In addition, the ice cream social served VA employees the opportunity to meet SA GRECC physicians, researchers and staff.

The director of the Geriatrics Center and Institute of Gerontology at the University of Michigan, Raymond Yung, MB, Ch.B., joined the 30-year celebration as a guest speaker. Dr. Yung acknowledged SA GRECC Director Nicolas Musi, MD, for his leadership role in integrating and strengthening the collaboration of translational research efforts between the SA GRECC and the University of Texas Health Science Center at San Antonio - specifically through the Sam and Ann Barshop Institute for Longevity and Aging Studies, and the Division of Geriatrics, Palliative and Gerontology.

Instituted in 1987 to serve older Veterans in Central and South Texas, SA GRECC activities focus on the broad themes of metabolism and inflammation. These activities aim at gaining new knowledge about the basic biology of aging, mechanisms regulating longevity, and understanding the pathophysiology of numerous age-related diseases that affect the lives of millions of older Veterans.

Local Contact: Paulina Forbes

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Evidence of Clinical Uncertainty? Site-Level Variation in Benzodiazepine Prescriptions to Patients with Limited Life Expectancy (Bronx GRECC)

Melissa Garrido, PhD is the recipient of a VA HSR&D Career Development Award to improve psychosocial care quality among seriously ill Veterans. Part of this work includes exploration of facility-level patterns of medication provision to hospitalized patients.

When prescribing benzodiazepines to patients with limited life expectancy, clinicians balance the need to manage breathlessness and agitation with the desire to minimize adverse events and complications from polypharmacy. However, there is little guidance on how best to use benzodiazepines for symptom control in seriously ill patients. A necessary first step to improving recommendations for their use is to have a better understanding of which medications are being prescribed and to whom. Of a national cohort of 35,094 Veterans with advanced cancer, heart failure, or chronic obstructive pulmonary disease who were hospitalized between 2012 and 2016 (mean age = 69), 16% received a benzodiazepine while hospitalized (most commonly lorazepam or midazolam). Benzodiazepine prescriptions were more likely among patients with depression, anxiety, past-year benzodiazepine use, in-hospital antipsychotic receipt, and among patients who died before discharge. However, after controlling for these characteristics, a 5-fold difference in the percentage of patients receiving benzodiazepines at different VA medical centers remained (5%-27%). Site-level differences in prescription rates may reflect clinical uncertainty in benzodiazepine use. High-quality symptom management for seriously ill patients requires an improved understanding of the patients for whom benzodiazepines are most likely to mitigate symptoms.

For more information, contact Dr. Melissa Garrido at (718) 584-9000, ext. 3804.

Local Contact
P: 718-584-9000, ext. 3853

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Helping Older Patients Exercise! (Little Rock GRECC)

Kalpana Padala, MD, a geriatrician at the Little Rock GRECC, is systematically breaking barriers to improve physical activity among older Veterans that need it most. She is making exercising fun to improve adherence. Although regular exercise improves gait and balance, older Veterans do not adhere to them. Over half of older Veterans discontinue an exercise program within six months of initiation due to various barriers. Dr. Padala studies exergames with Nintendo Wii-Fit and older Veterans are liking them. She uses a state-of-the-art gait and balance laboratory to discern subtle biomechanical changes resulting from the exercise program. She completed two pilot studies using Nintendo Wii-Fit. One pilot study showed that facility-based Wii-Fit exercises significantly improved balance compared to the computer-based cognitive exercises in a cohort of community dwelling older adults. The second study showed that home-based caregiver supervised Wii-Fit exercises significantly improved balance compared to walking in a cohort of community dwelling older adults with mild Alzheimer’s dementia. Adherence and engagement in the exercise programs were high in both studies.

For more information contact Dr. Padala.

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MoTrPAC (The Molecular Transducers of Physical Activity Consortium (Eastern Colorado GRECC)

The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a national research consortium that will characterize the molecular transducers altered by physical activity in humans. The goals of MoTrPAC are to study the molecular changes that occur during and after exercise, to advance the understanding of how physical activity improves and preserves health.

MoTrPAC includes 11 adult Clinical Centers that will recruit 2700 adults, aged 18+ years who are generally healthy and either sedentary (n=2400) or highly active (n=300). Clinical Centers are located at the Univ of Alabama Birmingham, Florida Hospital, Ball State Univ, Univ of Pittsburgh, Univ of Colorado Denver, Duke Univ, Wake Forest Univ, East Carolina Univ, Univ of Texas Medical Branch, University of Texas Health Sciences Center, and Pennington Biomedical Research Center. One Pediatric Center at the Univ of California Irvine will recruit 300 adolescents. All MoTrPAC participants will undergo an exercise session that includes sampling of blood, adipose tissue, and skeletal muscle. The sedentary participants will be randomized to undergo 12 weeks of exercise training or no-exercise control, and then repeat the exercise session. Parallel studies of rats will be conducted to interrogate not only blood, adipose, and muscle responses to exercise, but also those tissues that cannot be studied in humans. Biospecimens will undergo ‘omics’ analyses, including genomics, epigenomics, transcriptomics, proteomics, and metabolomics.

All data generated by MoTrPAC will be stored in a public resource that any researcher can access to investigate the molecular mechanisms for the health benefits of exercise. The plan is to have the protocol reviewed by the VA Central IRB to facilitate the inclusion of Veterans. More information about MoTrPAC can be found at

Local Contact: Dr. Wendy Kohrt
Phone: 303-724-1913

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Multi-sensory (MSE) Environments for Bathing Veterans with Dementia (Gainesville GRECC)

For veterans with dementia, and CLC staff, bathing can be a traumatic experience. Bathing in the CLC is commonly provided in large, cold communal bathing environments with standing-height tubs at various times of the day by a workforce that experiences constant turn over. Nothing about the experience resembles the relaxing experience typically found at home in their own environment. As a result, the patient may become agitated, making bathing difficult.

There is much debate regarding the best possible methods to manage agitation during assisted bathing. Non-pharmacological interventions are the preferred first line of treatment because pharmacological interventions care expensive, unsafe and unsuccessful.

Investigators at the Gainesville GRECC and the UF Colleges of Education and Design, Construction & Planning are conducting a study of multisensory environment (MSE) stimulation during bathing in patients residing in the dementia unit in the CLC at Lake City VAMC. The MSE stimulation is tailored to each patient and can include sight (light), sound (music), olfaction (aromatherapy), and touch (tactile). If successful, this approach could improve patient and staff satisfaction hygiene and hygiene among CLC patients with Dementia.

Local Contacts: Ron Shorr, MD and Lesa Lorusso

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New Hypertension Guidelines Incorporate SPRINT Results (Salt Lake City GRECC)

The new guideline for hypertension in adults established a lower threshold to define hypertension as a blood pressure in excess of 130/801. The new guideline incorporates outcomes from the Systolic Blood Pressure Intervention Trial’s (SPRINT) study that identified benefits among those randomized to intensive (a systolic blood pressure - SBP - treatment target of < 120 mmHg) relative to standard (a < 140 mmHg SBP target) management. The main results2 and outcomes specific to older adults (age 75 years and older)3 identified significant cardiovascular (CVD) and mortality benefits. These outcomes did not differ for the frailest subgroup or for those with impaired gait speed3. Accordingly, the SBP goal now recommended for adults age 60 years and older is 130 mm Hg1.

Two recent reports cite additional benefits demonstrating that the intensive treatment was well tolerated.4 Patient reported outcomes from the physical and mental components of the Veterans RAND 12-Item Health Survey and the Patient Health Questionnaire 9-item depression scale did not differ over time between treatment groups. These findings held in the most frail group of participants. Satisfaction with blood-pressure care was high in both treatment groups, and adherence to blood-pressure medications did not differ between groups. In addition, in a cost-effectiveness simulation study, the benefits identified with intensive SBP control occurred at costs below common willingness-to-pay thresholds per quality adjusted life year gained, regardless of whether benefits were reduced after 5 years or persisted for the patient’s remaining lifetime.5

1. Whelton PK, Carey RM, Aronow WS, et al. 2017 guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: J AmColl Cardiol. doi:10.1016/ j.jacc.2017.11
2. Wright JT, Jr., Williamson JD, Whelton PK, et al. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med 2015;373:2103-16.
3. Williamson JD, Supiano MA, Applegate WB, et al. Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged >75 Years: A Randomized Clinical Trial. JAMA 2016;315:2673-82.
4. Berlowitz DR, Foy CG, Kazis LE, et al. Effect of Intensive Blood-Pressure Treatment on Patient-Reported Outcomes. N Engl J Med 2017;377:733-44.
5. Bress AP, Bellows BK, King JB, et al. Cost-Effectiveness of Intensive versus Standard Blood-Pressure Control. N Engl J Med 2017;377:745-55.

Local Contact: Scott Capps, GRECC A/O

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Nutrient Intake and Hospitalization (Little Rock GRECC)

Older Veterans often become severely malnourished during hospitalization, leading to a range of complications and a higher risk of mortality. To prevent this from happening, inpatient programs need to closely monitor each patient’s nutrient intake. Yet most hospitals are not adequately staffed to do this. The Little Rock GRECC developed and studied a novel means for completing daily patient nutrient intake assessments in less than one-third the time required by traditional methods, and the new approach was found to be more accurate as well. The greater ease and improved accuracy facilitates identification of patients at elevated risk for becoming malnourished.

Anyone interested in this new approach to assessing nutrient intake can contact Dennis H. Sullivan, MD.

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Potential translational impacts of a plant derived compound on reducing a major risk factor for heart disease, diabetes, and non-alcohoholic fatty liver disease (Palo Alto GRECC)

Metabolic syndrome (MetS) is a cluster of metabolic risk factors such as increased blood pressure, high blood sugar, excess body fat around the waist and abnormal cholesterol or triglyceride levels. These risk factors are implicated in a number of health issues in older Veterans such as heart disease, stroke, diabetes and the common liver disease, nonalcoholic fatty liver disease (NAFLD). At present, there are no approved drugs to treat MetS associated risk factors. Recent studies from Dr. Salman Azhar’s laboratory provide evidence that a small molecule (i.e., Nordihydroguiaiaretic acid or NDGA), derived from the Creosote bush plant, improves several components of MetS in experimental animal models. Dr. Azhar’s laboratory has been directing much effort towards screening and testing synthetic derivatives of NDGA. One of the labs goals is determining target molecules with the best potential toward developing new drugs to treat one or more components of Mets; and therefore reduce several potent risk factors in the development of heart disease, diabetes and/or NAFLD, which affect many older Veterans.

Local Contact: Terri Huh, PhD, Assoc. Dir. of Education & Evaluation, Palo Alto GRECC
Phone: 650.493.5000 x67739

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Proteins Block Neuronal Death (San Antonio GRECC)

A number of aging-related neurological diseases such as stroke, Lou Gehrig's disease, and Alzheimer's disease, involve the death of neurons in the brain. The San Antonio GRECC recently described ferroptosis, a previously unrecognized mechanism of neuronal death. Even more exciting, the investigators identified a protein that disrupts this mechanism. Enhancing the activity and delivery of this protein might be a new approach for supporting healthy brain aging.

To find out more about this work, contact Dr. Nicolas Musi.

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Research Highlights (Minneapolis GRECC)

Dr. Cathy Kotz, PhD and Dr. Michael Lee, PhD, of the Minneapolis VA Medical Center GRECC are exploring ways to improve learning and memory in an animal model of Parkinson’s disease. Their focus is on manipulation of the neuropeptide orexin, the activity of which is significantly reduced or even lost during progression of many forms of dementia. Orexin is known to improve learning and memory, and thus the investigators propose that if orexin activity is restored and/or enhanced in Parkinson’s disease, there will be improvement in learning and memory. To date, the investigators have shown that animals made deficient in orexin by genetic manipulation have impairments in learning and memory tasks, and that infusions of orexin into memory centers of the brain in these animals reverses these deficits. The investigators are now moving these findings into a genetic model of Parkinson’s disease, to test whether infusions of orexin in these animals can improve deficits in their learning and memory profile. Instead of infusion of orexin into the brain, they plan to stimulate remaining orexin neurons “remotely” through the use of Designer Receptors Exclusively Activated by Designer Drugs (DREADD) approach. With this method, a designer receptor is introduced into the cell surface of the orexin neurons. This receptor is then activated by a designer drug that binds exclusively to that receptor, stimulating the orexin neurons. It is hoped that by stimulating the remaining orexin neurons with the designer drug, learning and memory will improve in these mice. This work was funded by VA BLRD in 2016.

Dr. Kotz is also collaborating with Dr. Patricia Bunney, PhD, a recent career development awardee in the GRECC at the Minneapolis VA Medical Center. Their work focuses on the biological basis for reductions in physical activity with aging and looking at ways to improve physical activity levels in aged mice. They are using the DREADD approach to understand how declines in various central nervous system pathways can lead to reductions in physical activity, and whether stimulation of these pathways using designer drugs can improve physical activity in normally aging mice. They are hoping to identify new therapeutic targets for age-induced obesity.

To learn more about this research, contact Dr. Cathy Kotz.

Local Contact: Ann Bolan, 612-467-2051.

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Warrior Wellness Study: Using Exercise to Promote Health & Wellness in Veterans with PTSD (Durham GREC)

Dr. Katherine Hall, a researcher with the Durham VA GRECC, is currently leading a 12- week pilot randomized controlled trial of supervised exercise for older Veterans with posttraumatic stress disorder (PTSD). Primary outcomes include PTSD symptoms, quality of life, and physical function.

In preparation for rolling out this study, interviews with older Veterans with PTSD were conducted. A dominant theme that emerged was that these Veterans were keen to be targeted for “wellness” interventions (instead of solely ‘cessation of negative behaviors’), and were excited about the prospect of being offered a chance to practice the warrior ethos of health and fitness.

A manuscript describing the development and implementation of this study will be published in the Translational Journal of the American College of Sports Medicine (March 2018). Although this study is still out in the field, preliminary results are encouraging: 90% of Veterans who have enrolled in the program have completed 12 weeks of exercise, attending 81% of the offered sessions (MWF, 09:00-10:30).
Local Contact:
Phone: (919)286-0411 x6734

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