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| ### *GRECC Annual Report: Fiscal Year [2005]{.underline}*             |
|                                                                       |
| ######## Part II: Accomplishments                                     |
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| This GRECC Annual Report covers [October 1, 2004-September 30,        |
| 2005]{.underline}: **the "Report Year"**.                             |
|                                                                       |
| This GRECC Annual Report reflects status and accomplishments of       |
| [**GRECC Core Staff \***only]{.underline}.                            |
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| **\*[GRECC Core Staff ]{.underline}**is limited to either **Primary   |
| Core**, **Affiliate Core**, or **Research Core**:                     |
|                                                                       |
| -   **Primary Core =** positions authorized by the original GRECC     |
|     allocation plus any addition in ceiling from VA Central Office    |
|     specifically designated for GRECC.                                |
|                                                                       |
| -   **Affiliated Core** = Staff who work full- or part-time in        |
|     [direct support]{.underline} of the GRECC's research, education   |
|     or clinical activity.                                             |
|                                                                       |
|     -   May be either "contributed" by the VA Medical Center or       |
|                                                                       |
|     -   May have been acquired through centralized                    |
|         enhancements/awards for programs\                             |
|         (e.g., Home-Based Primary Care, Geriatric Evaluation and      |
|         Management Program, etc.)                                     |
|                                                                       |
|     -   To be considered Affiliated Core, staff must be               |
|         organizationally aligned under the GRECC or specifically      |
|         identified by the Medical Center as **"GRECC-affiliated       |
|         staff."**                                                     |
|                                                                       |
| -   **Research Core** = Full-or part-time staff who devote 51% or     |
|     more of their total time to GRECC research and whose salaries are |
|     supported by research funds (either VA or non-VA). Includes all   |
|     GRECC staff whose salaries are paid from research funds, e.g.:    |
|                                                                       |
|     -   Associate Investigator                                        |
|                                                                       |
|     -   Assistant Research Scientist                                  |
|                                                                       |
|     -   Senior Research Career Scientist                              |
|                                                                       |
|     -   Research Career Scientist                                     |
|                                                                       |
|     -   Advanced Research Career Scientist.                           |
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| **1. GRECC NAME/LOCATION**                                            |
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| a.  **GRECC Name:** St. Louis VAMC GRECC, St .Louis, MO               |
|                                                                       |
| b.  **Location** *(facility, VISN)*: VA Heartland Network, VISN 15,   |
|     Kansas City, MO                                                   |
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| **2. CONTACT PERSON (if there are questions about this report)**      |
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| a.  **Name:** H. James Armbrecht, Ph.D./Linda M. Smith                |
|                                                                       |
| b.  **Position:** Associate Director, Evaluation/AO, GRECC            |
|                                                                       |
| c.  **Phone, e-mail:** 314-894-6510                                   |
|                                                                       |
| d.  [**Armbrecht.**james@med.va](mailto:Armbrecht.james@med.va).      |
|     <Smith.linda@med.va>.                                             |
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| **3. GRECC FOCUS AREA(S)**                                            |
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| GRECCs are required to conduct research in a basic biomedical area,   |
| an applied clinical area, and either a health services or             |
| rehabilitation topic. The number of specific research foci in each    |
| perspective should be limited to two or fewer.                        |
|                                                                       |
| Please enter a succinct phrase that best characterizes the focus      |
| area(s) recognized for your GRECC in the first two and either the     |
| third or fourth (or both) category below:                             |
|                                                                       |
| a.  **Basic Biomedical**: Physiological and metabolic concomitants of |
|     aging                                                             |
|                                                                       |
| b.  **Applied Clinical**: Effects of exercise and nutrition on        |
|     physiological and metabolic parameters                            |
|                                                                       |
| c.  **Health Services**: Health care utilization, program evaluation. |
|                                                                       |
| d.  **Rehabilitation**:                                               |
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| **4. ADMINISTRATION**                                                 |
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| a.  **GRECC Impact on Host VAMC in Report Year**\                     |
|     *(list the most important ways in which the GRECC has had         |
|     positive impact on the host VAMc\--i.e., how the GRECC has "made  |
|     a difference" locally. **Please limit your response to five ways  |
|     or fewer.** Please be as succinct as possible but specify the     |
|     GRECC contribution, what the impact was and whom it benefited,    |
|     where it occurred, and why it was important. **Please limit the   |
|     description of each bullet item to 5 lines or fewer**)*           |
|                                                                       |
| -   Staff education through weekly conferences. Doctors and other     |
|     health care professionals are educated through presentations of   |
|     specific topics in geriatric medicine and through weekly          |
|     Geriatric Grand Rounds.                                           |
|                                                                       |
| -   Active involvement in Executive Council of Medical Center,        |
|     Research and Development Committee, Animal Use Subcommittee, and  |
|     Research Safety Subcommittee. This contributes to the research    |
|     environment of the St. Louis VAMC.                                |
|                                                                       |
| -   Held the Annual Geriatric Summer Institute in June 2005. Numerous |
|     local VA personnel were trained in applied geriatrics.            |
|                                                                       |
| -   Maintenance of core animal facilities for senescence accelerated  |
|     mice (SAMP8), double transgenic Alzheimer's mouse model, and      |
|     nitric oxide synthatase knockout mice. These animals are          |
|     available to other researchers.                                   |
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| b.  **GRECC Impact on VISN in Report Year** *\                        |
|     (list the most important ways in which the GRECC has had positive |
|     impact on the host VISN\-- i.e., how the GRECC has "made a        |
|     difference "regionally. **Please limit your response to five ways |
|     or fewer.** Please be as succinct as possible but specify the     |
|     GRECC contribution, what the impact was and whom it benefited,    |
|     where it occurred, and why it was important. **Please limit the   |
|     description of each bullet item to 5 lines or fewer**)*           |
|                                                                       |
| -   Continued distribution of three new "Aging Successfully"          |
|     newsletters and clinical resources to each VAMC in VISN15. The    |
|     newsletter continues to provide simple clinical tools for the     |
|     diagnosis and management of common geriatric conditions.          |
|                                                                       |
| -   Continued distribution of SLU Mental Status (SLUMS) exam to other |
|     VAMCs. This exam makes health professionals more aware of mild    |
|     cognitive impairment.                                             |
|                                                                       |
| -   Distribution of CNAQ (Counsel on Nutrition Appetite               |
|     Questionnaire) to other VAMCs. This questionnaire screens for     |
|     loss of appetite and subsequent weight loss.                      |
|                                                                       |
| -   Holding of Disaster Preparedness Conference for seniors.          |
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| c.  **GRECC Trend-Setting Innovations since October 1,                |
|     [2000]{.underline}**\                                             |
|     *(list the most significant research, education or clinical       |
|     innovations originating in your GRECC in the past five years.     |
|     Please limit your response to five innovations or fewer. For each |
|     item, succinctly describe the innovation, specify the time frame  |
|     of its earliest impact, whom it benefited, where it occurred, and |
|     why it was important. **Please limit the comments concerning each |
|     innovation to 5 lines or fewer**)*:                               |
|                                                                       |
| -   New screening test for poor appetite (2003) (Morley). This        |
|     Counsel on Nutrition Appetite Questionnaire (CNAQ) screens for    |
|     loss of appetite and subsequent weight loss and allows earlier    |
|     intervention.                                                     |
|                                                                       |
| -   Evidence that triglycerides are responsible for leptin            |
|     resistance (2004) (Banks). These studies indicate that            |
|     triglycerides may interfere with the movement of leptin across    |
|     the blood-brain barrier and the suppression of appetite. These    |
|     findings may suggest new ways to treat obesity in the elderly.    |
|                                                                       |
| -   Characterization of hormonal changes contributing to age-related  |
|     osteoporosis (2001-2003) (Armbrecht). These studies indicate that |
|     there is decreased capacity of parathyroid hormone to stimulate   |
|     the renal production of the active form of vitamin D with age. In |
|     addition, there is an age-related decrease in the capacity of the |
|     active form of vitamin D to stimulate the absorption of calcium   |
|     in the diet by the small intestine. These findings may suggest    |
|     ways to increase calcium absorption and retard bone loss in the   |
|     elderly.                                                          |
|                                                                       |
| -   Reversal of memory deficits in SAMP8 mice by antibody and         |
|     antisense technology (2000-2004) (Morley, Farr, Kumar) Deficits   |
|     in learning and memory can be reversed in old SAMP8 mice to the   |
|     levels seen in young mice. This has been demonstrated by          |
|     injection of antibodies to beta-amyloid into the brain            |
|     hippocampus and by systemic administration of antisense RNA       |
|     against beta-amyloid production. This provides a potential        |
|     mechanism for retarding memory loss in the elderly by             |
|     non-invasive means.                                               |
|                                                                       |
| -   New screening tool for male sexual dysfunction (ADAM) (2004-2005) |
|     (Morley). This has been translated into over 50 languages and     |
|     increases awareness of sexual dysfunction in the elderly male.    |
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| **5. RESEARCH**                                                       |
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| a.  **Most Noteworthy Findings Published in Report Year by GRECC Core |
|     Staff as PI or CO-PI\                                             |
|     ***(Please list five or fewer. For each noteworthy finding,       |
|     include the GRECC Core Staff name(s), journal reference, and a    |
|     JARGON-FREE description of the finding and its clinical or other  |
|     significance. Please limit your description of each noteworthy    |
|     finding to five lines or fewer.)*                                 |
|                                                                       |
| -   [Treatments for Alzheimer's disease (AD).]{.underline} Our group  |
|     continues to explore the delivery of therapeutics to the brain    |
|     which may be useful in the treatment of AD. Much attention has    |
|     been focused on whether antibodies can reach the brain. This      |
|     study shows that small amounts of antibody enter the brain from   |
|     the blood, and it establishes the extracellular pathways as the   |
|     mechanism of entry. This study shows that antibodies may be       |
|     useful agents for the treatment of AD.                            |
|                                                                       |
| *Reference:* **Banks, W.A.**, P.Pagliari, R. Nakaoke, and **J.E.      |
| Morley**. Effects of a behaviorally active                            |
|                                                                       |
| antibody on the brain uptake and clearance of amyloid beta proteins.  |
| [Peptides]{.underline} 26: 287-294, 2005.                             |
|                                                                       |
| -   [Inflammation plays a role in many diseases associated with       |
|     aging]{.underline}. Age-related diseases include colitis,         |
|     hypertension, atherosclerosis, rheumatoid arthritis, and          |
|     Alzheimer's disease. Results demonstrate nitrosation by nitric    |
|     oxide being potentiated by peroxidases such as myeloperoxidase.   |
|     Therefore, nitrosation may be elevated at sites of neutrophil     |
|     infiltration. Understanding the oxidative and nitrosative         |
|     chemistry of inflammation may improve treatment or prevention of  |
|     these diseases.                                                   |
|                                                                       |
| *Reference*: **Lakshmi, V.M.**, Nauseef, W.M., and **Zenser, T.V.**   |
| Myeloperoxidase potentiates nitric                                    |
|                                                                       |
| oxide-mediated nitrosation. [J. Biol. Chem]{.underline}., 280:        |
| 1746-1753, 2005.                                                      |
|                                                                       |
| -   [The regulation of intestinal calcium channels changes with       |
|     age]{.underline}. Young rats placed on a low calcium diet         |
|     markedly increase intestinal calcium absorption while old rats do |
|     not. This study showed that the capacity of a low calcium diet to |
|     increase expression of intestinal calcium channels also declines  |
|     with age. Finding ways to increase the expression of calcium      |
|     channels, as well as intestinal calcium binding proteins, may     |
|     improve calcium absorption and retard bone loss.                  |
|                                                                       |
| *Reference:* Brown, A.J., Krits, I. and **Armbrecht, H.J.** Effect of |
| age, vitamin D, and calcium on                                        |
|                                                                       |
| the regulation of rat intestinal epithelial calcium channels. [Arch.  |
| Biochem. Biophys.]{.underline} 437:51-58,                             |
|                                                                       |
| 2005\.                                                                |
|                                                                       |
| -   [The action of Orexin-A is mediated through nitric                |
|     oxide.]{.underline} This study examined the role of orexin-A in   |
|     increasing food intake and the role of nitric oxide synthase      |
|     (NOS) as a modulator of this event. Orexin-A administered to      |
|     satiated mice produced a significant increase in food intake.     |
|     This action was blocked by a NOS inhibitor. Understanding the     |
|     pathways that control feeding behavior may lead to treatments for |
|     anorexia in the elderly.                                          |
|                                                                       |
| > *Reference:* **Farr, S.A.,** **Banks, W.A.**, **Kumar, V.B**. and   |
| > **Morley, J.E**. Orexin-A-induced feeding is dependent on nitric    |
| > oxide. [Peptides]{.underline} 2005: 26, 759-765.                    |
|                                                                       |
| -   [Dehydroepiandrosterone sulfate (DHEAS) has beneficial effects on |
|     cognition in SAMP8 mice with elevated beta amyloid]{.underline}.  |
|     DHEAS is a steroid that decreases with age. Low doses to young    |
|     mice can improve memory. This study showed that chronic           |
|     administration of DHEAS in drinking water improved learning and   |
|     memory in 12 month SAMP8 mice, but not in diabetic mice.          |
|     Understanding how cognition can be improved in aged mice may      |
|     suggest treatments for age-related memory loss.                   |
|                                                                       |
| > *Reference:* **Farr, S.A.,** **Banks, W.A.**, Uezu, K., Gaskin,     |
| > F.S. and **Morley, J.E**. DHEAS improves learning and memory in     |
| > aged SAMP8 mice but not in diabetic mice. [Life                     |
| > Sciences]{.underline} 2004: 75, 2775-2785.                          |
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| b.  **Most Noteworthy Findings Published in Report Year -- GRECC Core |
|     Staff as Co-Investigators on Projects with Non-GRECC PI\          |
|     ***(Please list five or fewer. For each noteworthy finding,       |
|     include the GRECC Core Staff name(s), journal reference, and a    |
|     JARGON-FREE description of the finding and its clinical or other  |
|     significance. Please limit your description of each noteworthy    |
|     finding to five lines or fewer)*                                  |
|                                                                       |
| -   [Treatment of brain cancers.]{.underline} An analog of growth     |
|     hormone-releasing hormone has previously been shown by AV Schally |
|     (Nobel Laureate at the New Orleans VA) to be an effective agent   |
|     against peripheral tumors. This study demonstrated that the       |
|     analog can also cross the blood-brain barrier and enter the       |
|     central nervous system very well. It is also resistant to enzyme  |
|     degradation. Hence, this compound may offer hope in the treatment |
|     of brain cancers.                                                 |
|                                                                       |
| > *Reference:* Jaeger, L.B., **W.A. Banks**, J.L. Varga, and A.V.     |
| > Schally. Antagonists of growth                                      |
| >                                                                     |
| > hormone-releasing hormone cross the blood-brain barrier: A          |
| > potential applicability to treatment of                             |
|                                                                       |
| brain tumors. [Proc. Natl. Acad. Sci. USA]{.underline}                |
| 102:12495-12500, 2005.                                                |
|                                                                       |
| -   [Low dietary calcium is a risk factor for colorectal              |
|     carcinogenesis]{.underline}. Epideniological data suggest a       |
|     protective role of calcium and vitamin D against colorectal       |
|     carcinogensis, but the mechanism is unknown. This study showed    |
|     that low dietary calcium induces an enzyme in the ascending colon |
|     that degrades the active form of vitamin D, which is known to     |
|     block excessive cell growth. Understanding the interaction        |
|     between calcium and vitamin D may suggest ways to reduce the risk |
|     of colon cancer.                                                  |
|                                                                       |
| *Reference:* Kallay, E., Bises, G., Bajna, E., Bieglmayer, C.,        |
| Gerdenitsch, W., Steffan, I., Kato, S.,                               |
|                                                                       |
| **Armbrecht, H.J.** and Cross, H.S. Colon-specific regulation of      |
| vitamin D hydroxylases -- A possible                                  |
|                                                                       |
| approach for tumor prevention. [Carcinogenesis]{.underline}           |
| 26:1581-1589, 2005.                                                   |
|                                                                       |
| -   [The antioxidant alpha lipoic acid reverses oxidative damage in   |
|     aged SAMP8 mice.]{.underline} It is well known that oxidative     |
|     damage occurs during Alzheimer's disease. Previously, we have     |
|     shown that alpha lipoic acid improves memory and reduces          |
|     oxidative damage. Here, we show that alpha lipoic acid reduces    |
|     oxidative damage as measured by proteomics. These results give    |
|     further support to the benefit of alpha lipoic acid in            |
|     age-related dementia.                                             |
|                                                                       |
| *Reference:* Poon, H.F., **Farr, S.A.,** Thongnookerd, V., Lynn,      |
| B.C., **Banks, W.A.**, **Morley, J.E.**,                              |
|                                                                       |
| Klein, J.B. & Butterfield, D.A. Proteomic analysis of specific brain  |
| proteins in aged SAMP8 mice                                           |
|                                                                       |
| treated with alaph-lipoic acid: implications for aging and            |
| age-related neurodegenerative disorders.                              |
|                                                                       |
| [Neurochem Int]{.underline}*.* 2005: 46, 159-168.                     |
|                                                                       |
| -   [Drug delivery to the central nervous system (CNS).]{.underline}  |
|     Many CNS diseases cannot be treated because of poor penetration   |
|     of otherwise effective drugs into the brain. In this paper, the   |
|     ability of free fatty acid conjugates to make impermeable or      |
|     poorly permeable drugs cross the blood-brain barrier (BBB)        |
|     studied. It was found that steric acidification greatly enhanced  |
|     the ability of two poorly permeable proteins to cross the BBB.    |
|     This strategy may allow the drug treatment of CNS diseases in the |
|     elderly.                                                          |
|                                                                       |
| *Reference:* Batrakova, E.V., S.V. Vinogradov, S.M. Robinson, M.L.    |
| Niehoff, **W.A. Banks**, and                                          |
|                                                                       |
| A.V. Kabanov. Polypeptide point modifications with fatty acids and    |
| amphipilic block copolymers for                                       |
|                                                                       |
| enhanced brain delivery. [Bioconjugate Chemistry]{.underline}         |
| 16:793-802, 2005.                                                     |
|                                                                       |
| -   [Antisense directed at the A-beta region of the APP peptide       |
|     reduces oxidative stress as measured by proteomics]{.underline}.  |
|     We have previously shown that antisense directed at the A-beta    |
|     region of the APP peptide, blocking the production of A-beta,     |
|     improves age-related deficits in learning and memory in SAMP8     |
|     mice. This study shows that antisense reverses oxidative damage   |
|     as measured by proteomics. These current findings give further    |
|     support to antisense as a treatment for Alzheimer's disease.      |
|                                                                       |
| *Reference:* Poon, H.F., **Farr, S.A**., **Banks, W.A.**, Pierce,     |
| W.M., Klein, J.B. and **Morley, J.E.**                                |
|                                                                       |
| Proteomic identification of less oxidized brain proteins in aged      |
| senescence-accelerated mice                                           |
|                                                                       |
| following administration of antisense oligonucleotide directed at the |
| A-beta region of amyloid                                              |
|                                                                       |
| precursor protein. [Brain Res. Mol. Brain Res.]{.underline} 2005:     |
| 138, 8-16.                                                            |
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| **6. EDUCATION**                                                      |
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| a.  **Innovations in Educational Activities Implemented During Report |
|     Year**\                                                           |
|     (*Please list up to five. For each, describe the innovation and   |
|     the context in which it was innovative. Please limit your         |
|     description of each innovation to five lines or fewer):*          |
|                                                                       |
| -   *Aging Successfully* Fall 2004, Vol XIV, No.3: Emergency          |
|     Preparedness: This 24-page issue concentrated on educating        |
|     healthcare professionals and patients about how to prepare for an |
|     emergency, natural or human-made.                                 |
|                                                                       |
| -   *Aging Successfully* Winter 2005, Vol XV, No.1: Gerontology       |
|     Education: What is the Evidence Base? This 24-page issue          |
|     concentrated on educating healthcare professionals and patients   |
|     about the evidence-based research that has been done on the uses  |
|     and limitations of various educational methodologies.             |
|                                                                       |
| -   *Aging Successfully* Summer 2005, Vol XV, No.2: Social and        |
|     Community Aspects of Aging. This 24-page issue concentrated on    |
|     educating healthcare professionals and patients about the effects |
|     that non-medical barriers have on the ability of an elder to age  |
|     successfully.                                                     |
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| b.  **Exportable Educational Products First Available for             |
|     Distribution in Report Year**\                                    |
|     *(Please list your most important products. Please limit to five. |
|     Your description of each item should succinctly summarize the     |
|     content, target audience, format, and product evaluation results  |
|     if any. You may include products developed in prior years ONLY IF |
|     THIS IS THE FIRST YEAR they have been available for distribution. |
|     Please limit each description to five lines or fewer)*:           |
|                                                                       |
| -   Emergency Preparedness kits designed for frail, home-bound and    |
|     nursing home patients.                                            |
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| **7. CLINICAL INNOVATIONS**                                           |
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| **NEW DEFINITION:** A "Clinical Innovation" is an untested,           |
| GRECC-initiated clinical effort that ideally is related to one of the |
| GRECC's research foci. A Clinical Innovation may be a wholly original |
| clinical program or an original aspect of or variation on an          |
| established program. A Clinical Innovation must incorporate an        |
| evaluation plan for assessing the innovation's efficacy so that, if   |
| the innovation is demonstrated to be an improvement over an existing  |
| approach to care, there is a basis on which it can be exported for    |
| implementation elsewhere.                                             |
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| a.  **Clinical Innovations Underway in Report Year**\                 |
|     *(list all Clinical Innovations underway during the report year.  |
|     For each, indicate whether the innovation is [N]{.underline}ew or |
|     [O]{.underline}ngoing in the report year. Please describe each    |
|     innovation in five lines or fewer)*:                              |
|                                                                       |
| -   Exporting of SLU Mental Status (SLUMS) exam to other VAMCs.       |
|     (Ongoing) This exam made health professionals more aware of mild  |
|     cognitive impairment.                                             |
|                                                                       |
| -   Exporting of Counsel on Nutrition Appetite Questionnaire (CNAQ)   |
|     to other VAMCs. (Ongoing) This questionnaire screens for loss of  |
|     appetite and subsequent weight loss.                              |
|                                                                       |
| -   Physician Leadership Academy held in January and July, 2005.      |
|     (Ongoing) This program continues to train physicians for          |
|     leadership roles in Geriatric Medicine.                           |
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| b.  **Evaluation Results of Clinical Innovations listed in the        |
|     preceding box\                                                    |
|     ***(for each clinical innovation listed in 7-a above, summarize   |
|     evaluation outcome(s) identified in the report year, in five      |
|     lines or fewer. Please specify "no evaluation results" for any    |
|     innovation for which that is the case)*                           |
|                                                                       |
| -   SLUMS -- Ongoing Recession Operating Characteristics (ROC)        |
|     analysis and improved patient diagnosis.                          |
|                                                                       |
| -   CNAQ -- Ongoing Recession Operating Characteristics (ROC)         |
|     analysis and improved patient diagnosis.                          |
|                                                                       |
| -   Physician Leadership Academy -- Effectiveness was evaluated via   |
|     post-conference questionnaire and e-mail.                         |
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| c.  **Clinical Innovation Exported in Report Year**\                  |
|     *(Please list up to five examples. In three lines or less for     |
|     each example, name or describe the innovation, identify the name  |
|     of the VA or non-VA facility to which it was exported, and the    |
|     method of export)*:                                               |
|                                                                       |
| -   Mailed SLU Mental Status (SLUMS) exam booklets to all GRECCs, all |
|     VA medical directors and chiefs of staff, all medical school      |
|     deans, and all members of the American Geriatrics Society. This   |
|     exam makes health professionals more aware of mild cognitive      |
|     impairment.                                                       |
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| **8. CONSULTATION AND OUTREACH**                                      |
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| **DEFINITIONS:**                                                      |
|                                                                       |
| **"Consultation"** for this section of the report has occurred when   |
| GRECC staff has materially assisted in the development of a non-GRECC |
| research, education or clinical program **[within the host            |
| VAMC.]{.underline}**                                                  |
|                                                                       |
| **"Outreach"** for this section of the report has occurred when GRECC |
| staff has materially assisted in the development of a non-GRECC       |
| research, education or clinical program **[at a facility other than   |
| the host VAMC.]{.underline}**                                         |
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| **Note:**                                                             |
|                                                                       |
| **for the 2005 Annual Report,**                                       |
|                                                                       |
| **Consultation and Outreach activity**                                |
|                                                                       |
| **will NOT be reported here.**                                        |
|                                                                       |
| **It will be reported via the Electronic Annual report Data Base.**   |
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