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+----------------------------------------------------------+---+---+---+---+
| ### GERIATRIC RESEARCH, EDUCATION AND CLINICAL CENTER    |   |   |   |   |
|                                                          |   |   |   |   |
| ### *Annual Report: Fiscal Year [2006]{.underline}*      |   |   |   |   |
|                                                          |   |   |   |   |
| ######## Part II: Accomplishments                        |   |   |   |   |
+----------------------------------------------------------+---+---+---+---+
| **NOTE:** The **GRECC Annual Report** reflects status    |   |   |   |   |
| and accomplishments of **[GRECC Core Staff]{.underline}  |   |   |   |   |
| \*** (as defined below) [only]{.underline}. The          |   |   |   |   |
| **"Report Year"** is from [October 1, 2005 through       |   |   |   |   |
| September 30, 2006]{.underline}.                         |   |   |   |   |
|                                                          |   |   |   |   |
| You are welcome to use this report format for your own   |   |   |   |   |
| internal reporting purposes,                             |   |   |   |   |
|                                                          |   |   |   |   |
| in which case you may exceed the recommended limits of   |   |   |   |   |
| numbers of responses and their length                    |   |   |   |   |
|                                                          |   |   |   |   |
| ("list no more than..." "Describe the three most         |   |   |   |   |
| important..." "limit your response to five lines or      |   |   |   |   |
| fewer")                                                  |   |   |   |   |
|                                                          |   |   |   |   |
| ***\-\--BUT\--***                                        |   |   |   |   |
|                                                          |   |   |   |   |
| [Please limit **to ten pages or fewer** the version      |   |   |   |   |
| **SUBMITTED TO VACO** **.**]{.mark}                      |   |   |   |   |
+----------------------------------------------------------+---+---+---+---+
| **\*[GRECC Core Staff ]{.underline}**is limited to       |   |   |   |   |
| either **Primary Core**, **Affiliated 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.              |   |   |   |   |
+----------------------------------------------------------+---+---+---+---+
| **[IMPORTANT:]{.underline} Throughout this report,       |   |   |   |   |
| please AVOID/MINIMIZE JARGON. Each response is much more |   |   |   |   |
| likely to be included in secondary communications        |   |   |   |   |
| derived from the Annual Reports if it can be readily     |   |   |   |   |
| understood by a non-technical readership.**              |   |   |   |   |
+----------------------------------------------------------+---+---+---+---+
| **1. GRECC NAME/LOCATION**                               |   |   |   |   |
+----------------------------------------------------------+---+---+---+---+
| a.  **GRECC Name:** VAPSHCS                              |   |   |   |   |
|                                                          |   |   |   |   |
| b.  **Location** *(facility, VISN)*: Seattle and         |   |   |   |   |
|     American Lake, VISN 20                               |   |   |   |   |
+----------------------------------------------------------+---+---+---+---+
| **2. CONTACT PERSON**                                    |   |   |   |   |
+----------------------------------------------------------+---+---+---+---+
| a.  **Name:** Chris Foster                               |   |   |   |   |
|                                                          |   |   |   |   |
| b.  **Position:** Administrative Officer                 |   |   |   |   |
|                                                          |   |   |   |   |
| c.  **Phone, e-mail:** (206) 764-2842                    |   |   |   |   |
|     chris.foster@med.va.gov                              |   |   |   |   |
+----------------------------------------------------------+---+---+---+---+
| **3. GRECC FOCUS AREA(S)**                               |   |   |   |   |
+----------------------------------------------------------+---+---+---+---+
| **NOTE:** Please succinctly list your GRECC's Focus      |   |   |   |   |
| Area(s), one per line below. After each focus area       |   |   |   |   |
| listed, please indicate with a check mark (****) which  |   |   |   |   |
| of the research type(s) suitably describes the work      |   |   |   |   |
| conducted (including planning, implementation, analysis, |   |   |   |   |
| and dissemination/publication) within that focus during  |   |   |   |   |
| the Report Year. Add additional lines by positioning     |   |   |   |   |
| your cursor at the lower right side of the table and     |   |   |   |   |
| striking the "Tab" key.                                  |   |   |   |   |
+----------------------------------------------------------+---+---+---+---+
| **GRECC Focus Area**                                     | * |   |   |   |
|                                                          | * |   |   |   |
|                                                          | R |   |   |   |
|                                                          | e |   |   |   |
|                                                          | s |   |   |   |
|                                                          | e |   |   |   |
|                                                          | a |   |   |   |
|                                                          | r |   |   |   |
|                                                          | c |   |   |   |
|                                                          | h |   |   |   |
|                                                          | T |   |   |   |
|                                                          | y |   |   |   |
|                                                          | p |   |   |   |
|                                                          | e |   |   |   |
|                                                          | * |   |   |   |
|                                                          | * |   |   |   |
+----------------------------------------------------------+---+---+---+---+
|                                                          | > | > | > | > |
|                                                          |   |   |   |   |
|                                                          | * | * | * | * |
|                                                          | * | * | * | * |
|                                                          | B | A | H | R |
|                                                          | a | p | e | e |
|                                                          | s | p | a | h |
|                                                          | i | l | l | a |
|                                                          | c | i | t | b |
|                                                          | > | e | h | i |
|                                                          |   | d | > | l |
|                                                          | B | > |   | i |
|                                                          | i |   | S | t |
|                                                          | o | C | e | a |
|                                                          | m | l | e | t |
|                                                          | e | i | r | i |
|                                                          | d | n | v | o |
|                                                          | i | i | i | n |
|                                                          | c | c | c | * |
|                                                          | a | a | e | * |
|                                                          | l | l | s |   |
|                                                          | * | * | * |   |
|                                                          | * | * | * |   |
+----------------------------------------------------------+---+---+---+---+
| ***Neurobiologic and Neuroendocrine Aspects of Aging***  | * |   |   |   |
|                                                          | * |   |   |   |
|                                                          | X |   |   |   |
|                                                          | * |   |   |   |
|                                                          | * |   |   |   |
+----------------------------------------------------------+---+---+---+---+
| ***Metabolic Diseases and Cognitive/Sensory              |   | * |   |   |
| Impairment***                                            |   | * |   |   |
|                                                          |   | X |   |   |
|                                                          |   | * |   |   |
|                                                          |   | * |   |   |
+----------------------------------------------------------+---+---+---+---+
| **Bioethical Aspects of Medical Decision Making and      |   |   | * |   |
| Palliative Care: Ethical Issues in palliative and end of |   |   | * |   |
| life care.**                                             |   |   | X |   |
|                                                          |   |   | * |   |
|                                                          |   |   | * |   |
+----------------------------------------------------------+---+---+---+---+
|                                                          |   |   |   |   |
+----------------------------------------------------------+---+---+---+---+

+-----------------------------------------------------------------------+
| **4. ADMINISTRATION**                                                 |
+-----------------------------------------------------------------------+
| a.  **GRECC Impact on Host VAMC in Report Year***: list **the**       |
|     **most important ways** in which the GRECC has had specific       |
|     impact on **host VAMC's** research, staff education, program      |
|     evaluation, or clinical care improvements for elderly veterans    |
|     (i.e., how the GRECC has "made a difference" in these areas       |
|     within the entire host VAMC) during the Report Year. **Please     |
|     limit your response to [5 or fewer]{.underline} "ways"; and       |
|     please limit your description of each of the five "ways" to [five |
|     lines or fewer]{.underline}. ***                                  |
|                                                                       |
| -   GRECC investigators invested research dollars to purchase         |
|     laboratory equipment in collaboration with the host VAMC for use  |
|     by all VAPSHCS researchers.                                       |
|                                                                       |
| -   GRECC Director served as chair of the R&D Committee               |
|                                                                       |
| -   The GRECC increased its consultative services for the host VAMC,  |
|     by providing cognitive disorders, memory disorders and geriatric  |
|     psychiatry services for primary care patients.                    |
|                                                                       |
| GRECC Clinical Director serves as Director of the Clinical Research   |
| Unit and Chair of the Conflict of interest committee.                 |
+-----------------------------------------------------------------------+
| b.  **GRECC Impact on VISN in the Report Year:** *list **the** **most |
|     important ways** in which the GRECC has had specific impact on    |
|     the **host** **VISN's** research, staff education, program        |
|     evaluation, or clinical care improvements for elderly veterans    |
|     (i.e., how the GRECC has "made a difference" in these areas       |
|     within the entire host VISN) during the rating period. **Please   |
|     limit your response to [5 or fewer]{.underline} "ways"; and       |
|     please limit your description of each of the five "ways" to [five |
|     lines or fewer]{.underline}. ***                                  |
|                                                                       |
| -   **Ethics:** The GRECC continues to have a major role in the VISN  |
|     Ethics Advisory Board , providing key input and consultation to   |
|     the Network Director and VISN Executive Leadership Council.       |
|                                                                       |
| GRECC Investigator **Dr Cyrus Zabetian** collaborates with the VISN   |
| PADRECC on several Parkinson related research programs.               |
+-----------------------------------------------------------------------+
| c.  **GRECC Trend-Setting Innovations since October 1,                |
|     [2001]{.underline}**: *list **the** **most significant** GRECC    |
|     research, education or clinical innovations in the past five      |
|     years. For each item, provide date or date range, GRECC core      |
|     staff responsible, and a description. **Please limit your         |
|     response to 5 or fewer innovations; and please limit each of the  |
|     five innovation descriptions to five lines or fewer. ***          |
|                                                                       |
| -   **Ethics Program:** Completed pilot- and field-testing of a Staff |
|     Survey on Clinical and Organizational Ethics for the National     |
|     Center for Ethics in Health Care (VHA). This staff survey         |
|     assesses clinicians' and managers' perceptions of local ethics    |
|     practices, knowledge of ethics standards, and perceptions of      |
|     institutional factors that influence ethics practices. The survey |
|     will be incorporated into a new initiative from VACO in FY 05 to  |
|     promote integrated ethics programs in VHA facilities. The staff   |
|     survey is intended to provide information to facility leadership  |
|     so that quality improvement initiatives are targeted to improve   |
|     ethics practices.                                                 |
|                                                                       |
| -   **Electronic Informed Consent**. Dr. Pearlman and his Ethics      |
|     Program staff have been working with Ethics Center (VHA) staff    |
|     and Dialog Medical in pilot testing an electronic consent         |
|     software package at five VHA facilities. The software program     |
|     aids the informed consent process by (a) providing guidance to    |
|     the process, (b) ensuring that the process and documentation      |
|     matches VHA policy and ethical standards, (c) providing           |
|     standardized educational materials for patients, (d) permitting   |
|     electronic signatures, and (e) simultaneously developing a        |
|     progress note that accompanies the consent form. The results of   |
|     the pilot testing will be sent to the National Leadership Board   |
|     in early 2004 and help determine whether VHA institutes a         |
|     national electronic informed consent program.                     |
|                                                                       |
| -   **Memory Disorders Clinic/Memory Wellness Center.** GRECC         |
|     Associate Director for Operations, Suzanne Craft, PhD, has been   |
|     instrumental in establishing the GRECC Memory Disorder Clinic     |
|     (MDC). The MDC is located at the American Lake campus and         |
|     developed as part of Dr Crafts clinical research memory           |
|     disorders. The MDC provides Gero-psychology consultation to the   |
|     VAMC and provides a platform for continued clinical research by   |
|     Dr Craft and associates.                                          |
|                                                                       |
| #                                                                     |
|                                                                       |
| -   **Diagnosing Dementia using Telemedicine Technology:**            |
|                                                                       |
| The GRECC conducted a pilot study to see if telemedicine could        |
| provide reliable, accurate geriatric consultative services to         |
| evaluate veterans for dementia who were residing at remote sites at   |
| Veterans Homes. We found that the telemedicine examination was as     |
| accurate as an in-person clinical examination in establishing the     |
| diagnosis of dementia. Moreover, the subjects reported a high degree  |
| of satisfaction with the telemedicine experience and that they would  |
| like to have further care through telemedicine in the future. Another |
| benefit of the project was that the medical staff at the Residential  |
| Veterans Homes had improved communication and increased accessibility |
| to physicians at the VA Puget Sound Health Care System                |
+-----------------------------------------------------------------------+
| **5. RESEARCH**                                                       |
+-----------------------------------------------------------------------+
| **a. Key Findings Published in the Report Year on projects for which  |
| GRECC Core Staff was PI or Co-PI:\                                    |
| ***list **five or fewer;** for each item provide GRECC Core Staff     |
| name(s), journal reference, and description of topic/                 |
| method/results/clinical significance.* *Please limit each response to |
| [5 lines or fewer]{.underline}.*                                      |
|                                                                       |
| [Li G, Shofer JB, Kukull WA, Peskind ER, Tsuang DW, **Breitner JC**,  |
| McCormick W, Bowen JD, Teri L, **Schellenberg GD,** Larson            |
| EB.]                                                                  |
| (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve |
| &dopt=AbstractPlus&list_uids=16217057&query_hl=1&itool=pubmed_docsum) |
| [Related                                                              |
| Articles,](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=pubm   |
| ed_DocSum&db=pubmed&cmd=Display&dopt=pubmed_pubmed&from_uid=16217057) |
| ![](media/image2.png){width="0.20833333333333334in"                   |
| height="0.15625in"}[Links](javascript:PopUpMenu2_Set(Menu16217057);)  |
| Serum cholesterol and risk of Alzheimer disease: a community-based    |
| cohort study.\                                                        |
| [Neurology]{.underline}. 2005 Oct 11;65(7):1045-50.                   |
|                                                                       |
|  **GRECC Core Staff: Breitner JC, Schellenberg TD**                   |
|                                                                       |
| In a large, longitudinal cohort study, the data do not support an     |
| association between serum total cholesterol or high density           |
| lipoprotein in late life and subsequent risk of dementia or Alzheimer |
| disease (AD). The increased risk of AD with APOE-epsilon4 is probably |
| not mediated by serum total cholesterol levels.                       |
|                                                                       |
|                                                                       |
|                                                                       |
| **Brickell KL**, Steinbart EJ, Rumbaugh M, Payami H, **Schellenberg   |
| GD**, Van Deerlin V, Yuan W, **Bird TD**. Early Onset Alzheimer's     |
| Disease In Families With Late Onset: A Potential Important Subtype Of |
| Familial Alzheimer's Disease. [Arch Neurol]{.underline},              |
| 63:1307-1311, 2006.                                                   |
|                                                                       |
| **GRECC Core Staff: Schellenberg GD and Bird TD**                     |
|                                                                       |
| A study of 136 families with late-onset AD showed that 24% had an     |
| individual with early-onset AD (less than 60 years) and not fully     |
| explained by ApoE genotype.  These families may have a strong         |
| concentration of genetic factors influencing AD.                      |
|                                                                       |
| Wu, JD Haugk, K Woodke, L Nelson, P, Coleman, I **Plymate, SR**. 2006 |
|                                                                       |
| Interaction of IGF signaling and the androgen receptor in prostate    |
| cancer progression. [J Cell Biochem]{.underline}. 99(2):392-401.      |
|                                                                       |
| This work demonstrates the role of the insulin-like growth factor     |
| receptor and its effects on androgen receptor translocation by        |
| altering phosphorylation of the AR in prostate cancer progression.    |
|                                                                       |
| **GRECC Core Staff: Plymate SR**                                      |
|                                                                       |
| **Wolden-Hanson, T** (2006) Mechanisms of the Anorexia of Aging in    |
| the Brown Norway Rat. [*Physiology and Behavior*]{.underline} 88(3):  |
| 267-276                                                               |
|                                                                       |
| -     This report summarizes research into the nueroendocrine         |
|     contributions to the anorexia of aging, and reports that          |
|     peripheral injections of the \"hunger hormone\" ghrelin are as    |
|     effective in increasing food intake in aging rats as in younger   |
|     animals.                                                          |
|                                                                       |
| **GRECC Core Staff: Wolden-Hanson, T**                                |
|                                                                       |
| **Quinn LS**, Strait-Bodey L, Anderson BG, Argiles JM, Havel PJ.      |
| Interleukin-15 stimulates adiponectin secretion by 3T3-L1 adipocytes: |
| Evidence for a skeletal muscle-to-fat signaling pathway. [Cell Biol.  |
| Int]{.underline}. 2005;29:449-457.                                    |
|                                                                       |
| **GRECC Core Staff:** **L.S. Quinn**                                  |
|                                                                       |
| **Zabetian CP**, Hutter CM, Yearout D, Lopez AN, Factor SA, Griffith  |
| A, Leis BC, Bird TD, Nutt JG, Higgins DS, Roberts JW, Kay DM, Edwards |
| KL, Samii A, Payami H (2006) *LRRK2* G2019S in Families with          |
| Parkinson Disease Who Originated from Europe and the Middle East:     |
| Evidence of Two Distinct Founding Events Beginning Two Millennia Ago. |
| *[Am J Hum Genet]{.underline}* 79:752-758                             |
|                                                                       |
| This study provided evidence that the most common disease-causing     |
| mutation (*LRRK2* G2019S) among all neurodegenerative disorders       |
| identified to date: (1) is much older than previously recognized, (2) |
| is distributed worldwide, and (3) likely arose independently in at    |
| least three distinct human populations.                               |
|                                                                       |
| **GRECC Core Staff: Zabetian CP**                                     |
|                                                                       |
| **Shores Molly M**, Matsumoto Alvin M, Sloan Kevin L, and Kivlahan    |
| Daniel R.  Low serum testosterone levels and mortality in male        |
| veterans.  Archives of Internal Medicine 2006;166:1660-1663.          |
|                                                                       |
| This study of 858 male veterans found that low testosterone levels    |
| significantly increased the risk of dying compared to men with normal |
| testosterone levels, over an average follow-up time of 4 years.  This |
| increased risk for death in men with low testosterone persisted even  |
| after statistically adjusting for the effects of age, weight and      |
| overall medical illness.                                              |
|                                                                       |
| **GRECC Core Staff: Shores Molly M**                                  |
|                                                                       |
| **Kraemer, B**.**C**., Burgess, J.K., Chen, J.H., Thomas, J.H., and   |
| **Schellenberg, G.D**. (2006) Molecular pathways that influence human |
| tau-induced pathology in Caenorhabditis elegans. [Hum Mol             |
| Genet]{.underline}, 15,1483-96                                        |
|                                                                       |
| Unfolded protein response is required for prevention of tau           |
| neurotoxicity in a C. elegans model of Tauopathy.                     |
|                                                                       |
| ·          Lack of Protein Phosphatase 2A exacerbates tau             |
| neurotoxicity in a C. elegans model of Tauopathy.                     |
|                                                                       |
|  ·          Depletion of the homolog of Dynamin binding protein       |
| exacerbates tau neurotoxicity in C. elegans.                          |
|                                                                       |
|  ·          Decreased chaperone levels increase the effects of toxic  |
| tau in neurons.                                                       |
|                                                                       |
| All findings above are the results of a genome wide RNAi screen to    |
| identify genes that normally act to prevent or detoxify pathological  |
| tau in a *C. elegans* model of tauopathy.  The role these genes play  |
| in authentic human disease is being explored.                         |
|                                                                       |
| **GRECC Core Staff: Kraemer, BC, Schellenberg GD**                    |
+-----------------------------------------------------------------------+
| **b. Key Findings Published in the Report Year on work in which GRECC |
| Core Staff served as Co-Investigators to a Non-GRECC PI:** *list      |
| **five or fewer**; for each item provide GRECC Core Staff name(s),    |
| journal reference, and description of topic/method/results/clinical   |
| significance. Please limit each response to [5 lines or               |
| fewer]{.underline}.*                                                  |
|                                                                       |
| [Khachaturian AS, Zandi PP, Lyketsos CG, Hayden KM, Skoog I, Norton   |
| MC, Tschanz JT, Mayer LS, Welsh-Bohmer KA, **Breitner                 |
| JC**.](                                                               |
| http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve& |
| dopt=AbstractPlus&list_uids=16533956&query_hl=1&itool=pubmed_docsum)  |
| Antihypertensive medication use and incident Alzheimer disease: the   |
| Cache County Study.\                                                  |
| [Arch Neurol]{.underline}. 2006 May;63(5):686-92. Epub 2006 Mar 13.   |
|                                                                       |
| ** GRECC Core Staff: Breitner JC**                                    |
|                                                                       |
| Suggests that potassium sparing diuretics may protect against onset   |
| of Alzhiemer\'s disease.                                              |
|                                                                       |
|                                                                       |
|                                                                       |
| [Lyketsos CG, Toone L, Tschanz J, Corcoran C, Norton M, Zandi P,      |
| Munger R, **Breitner JC**, Welsh-Bohmer K; Cache County Study         |
| Group.]                                                               |
| (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve |
| &dopt=AbstractPlus&list_uids=16645936&query_hl=1&itool=pubmed_docsum) |
| [Related                                                              |
| Articles,](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=pubm   |
| ed_DocSum&db=pubmed&cmd=Display&dopt=pubmed_pubmed&from_uid=16645936) |
| ![](media/image2.png){width="0.20833333333333334in"                   |
| height="0.15625in"}[Links](javascript:PopUpMenu2_Set(Menu16645936);)  |
| A population-based study of the association between coronary artery   |
| bypass graft surgery (CABG) and cognitive decline: the Cache County   |
| study.\                                                               |
| [Int J Geriatr Psychiatry]{.underline}. 2006 Jun;21(6):509-18.        |
|                                                                       |
|  **GRECC Core Staff: Breitner JC**                                    |
|                                                                       |
| CABG surgery is associated with accelerated cognitive decline more    |
| than five years after the procedure in a long-lived population. This  |
| decline is small and its clinical significance is uncertain. We could |
| not find an association between CABG and decline in the first five    |
| post-operative years.                                                 |
|                                                                       |
|                                                                       |
|                                                                       |
| Hodapp JA, Carter GT, Lipe H, Michelson S, Kraft GH, **Bird TD**.     |
| Double trouble in hereditary neuropathy: concomitant mutations in the |
| PMP-22 gene and another gene produce novel phenotypes. [Archives      |
| Neurology]{.underline}, 63:112-117, 2006.                             |
|                                                                       |
| **GRECC Core Staff: Bird, TD**                                        |
|                                                                       |
| Three families each had individuals with severe neuromuscular disease |
| caused by two separate                                                |
|                                                                       |
| genetic mutations that included the PMP-22 gene and one other gene.   |
|  This emphasizes the need                                             |
|                                                                       |
| to recognize double mutations in persons with severe progressive      |
| neurological phenotypes.                                              |
|                                                                       |
| Wilson HM, Lesnikov V, **Plymate SR**, Ward J, Deeg HJ. High IGFBP-3  |
| levels in marrow plasma in early-stage MDS: effects on apoptosis and  |
| hemopoiesis. [Leukemia.]{.underline} 2005 Apr;19(4):580-5.            |
|                                                                       |
| **GRECC CORE - S. Plymate**                                           |
|                                                                       |
| This study shows that IGFBP-3 is associated with retinoid induced     |
| cell death in myelodysplastic syndrome.                               |
|                                                                       |
| -                                                                     |
|                                                                       |
| Busquets S, Figueras MT, Meijsing S, Carbo N, **Quinn LS**, Almendro  |
| V, Argiles JM, Lopez-Soriano FJ. Interleukin-15 decreases proteolysis |
| in skeletal muscle: A direct effect. [Int. J. Molec.                  |
| Med]{.underline}. 2005;16:471-476.                                    |
|                                                                       |
| **GRECC Core staff:** **L.S. Quinn**                                  |
|                                                                       |
| Elbaz A, Nelson LM, Payami H, Ioannidis JP, Fiske BK, Annesi G, Belin |
| AC, Factor SA, Ferrarese C, Hadjigeorgiou GM, Higgins DS, Kawakami H, |
| Krüger R, Marder KS, Mayeux RP, Mellick GD, Nutt JG, Ritz B, Samii A, |
| Tanner CM, Van Broeckhoven C, Van Den Eeden SK, Wirdefeldt K,         |
| **Zabetian CP**, Dehem M, Montimurro JS, Southwick A, Myers RM,       |
| Trikalinos TA (2006) Lack of replication of thirteen                  |
| single-nucleotide polymorphisms implicated in Parkinson's disease: a  |
| large-scale international study. *[Lancet Neurol]{.underline}* 5:     |
| 917-923                                                               |
|                                                                       |
| This was by far the largest genetics study ever conducted in          |
| Parkinson\'s disease (PD).  The data definitively demonstrated        |
| that several new PD-genes reported last year from the                 |
| first genome-wide association analysis performed in PD were all false |
| positives.                                                            |
|                                                                       |
| **GRECC Core Staff: Zabetian CP**                                     |
|                                                                       |
| Page ST, **Plymate SR**, Bremner WJ, **Matsumoto AM**, Hess DL, Lin   |
| DW, Amory JK, Nelson                                                  |
|                                                                       |
| PS, Wu JD. Effect of medical castration on CD4+ CD25+ T cells, CD8+ T |
| cell IFN-gamma                                                        |
|                                                                       |
| expression, and NK cells: a physiological role for testosterone       |
| and/or its metabolites. [Am J Physiol Endocrinol Metab]{.underline}   |
| 2006;290:E856-E863.                                                   |
|                                                                       |
| **GRECC Core Staff: Plymate SR, Matusmoto AM**                        |
|                                                                       |
| A randomized, placebo-controlled trial was conducted to investigate   |
| the role of testosterone in modulating cellular immune function. A    |
| small number of healthy middle-aged men were treated with placebo, a  |
| gonadotropin-releasing hormone (GnRH) antagonist to induce medical    |
| castration, or GnRH antagonist in combination with T replacement.     |
| Medical castration significantly reduced and testosterone treatment   |
| restored the percentage of regulatory immune white blood cells (T     |
| cells), decreased the activation of cytotoxic T cells, and increased  |
| the percentage of nature killer T cells. These results suggest that   |
| testosterone and/or its metabolites may help to maintain the          |
| physiological balance of autoimmunity and protective immunity by      |
| preserving the number of regulatory T cells and activation of         |
| cytotoxic T cells.                                                    |
|                                                                       |
| Li G, Cherrier MM, Tsuang DW, Petrie EC, Colasurdo EA, **Craft S,     |
| Schellenberg GD**, Peskind ER, Raskind MA, **Wilkinson CW**. Salivary |
| cortisol and memory function in human aging. [Neurobiol               |
| Aging]{.underline} 27:1705-1714, 2006.                                |
|                                                                       |
| The association of salivary cortisol concentrations with cognitive    |
| changes was measured in a 3-year longitudinal study. Elevated         |
| cortisol levels were significantly associated with poorer performance |
| on declarative memory and executive function tasks. High cortisol     |
| levels in non-demented older persons predict a decline in memory      |
| function over the next three years.                                   |
|                                                                       |
| **GRECC Core Staff: Craft, Schellenberg, Wilkinson**                  |
+-----------------------------------------------------------------------+
| **6. EDUCATION**                                                      |
+-----------------------------------------------------------------------+
| **NOTE**: **DO NOT** list trainee and conference data                 |
| here**\--**those data are reported in the GRECC Electronic Database.  |
|                                                                       |
| **NOTE:** You may list educational activities here even if they were  |
| supported by funds that qualified for inclusion in the ePROMISE       |
| (RDIS) database if you wish.                                          |
+-----------------------------------------------------------------------+
| **Innovations in Educational Activities Implemented during the Report |
| Year** *(list five or fewer. Please limit each item to [5 lines or    |
| fewer]{.underline} and include clarification of how each activity is  |
| innovative.)*                                                         |
|                                                                       |
| -   During FY 2006, the VAPSHCS GRECC continued to make educational   |
|     outreach programs available to all eight VISN 20 medical centers  |
|     through the use of VTels The eight programs received excellent    |
|     evaluations from each VISN 20 sites. These programs were          |
|     accredited for Category I CME, as well as CEUs for nursing,       |
|     social work and psychology through the on-going partnership with  |
|     the Boise EES. This successful collaboration continues to be a    |
|     great value to the programs.                                      |
|                                                                       |
| -   The VAPSHCS GRECC continued to present a **Fall and Spring        |
|     seminar series**, hosting several prominent researchers and       |
|     clinicians in the field of Alzheimer's and other                  |
|     Neurodegenerative diseases. The VAPSHCE hosted 101 educational    |
|     seminars and provided local continuing educational hours to 1580  |
|     VAPSHCS and University of Washington Staff. Plans for FY 2006     |
|     include continuing the seminar series and applying for Category I |
|     CME hours.                                                        |
|                                                                       |
| -   The redesigned GRECC national newsletter increased it's focus on  |
|     more in-depth coverage of outstanding research, clinical and      |
|     education accomplishments of individual GRECC members, as well as |
|     coverage of issues of general interest to all GRECC's. The Fall   |
|     2006 issue included a survey on readership and interests, which   |
|     was sent to 1000 recipients across the country and will be used   |
|     to improve the format of the forum.                               |
|                                                                       |
| -   VAPSHCS GRECC continued to strengthen partnerships with local,    |
|     regional, and national health care organizations by sponsorship   |
|     and hosting of conferences and lectures. These events include an  |
|     Ethics Forum presented once per quarter, co-coordination of Grand |
|     Rounds and research seminars (i.e., Parkinson's disease) at       |
|     several area teaching hospitals.                                  |
+-----------------------------------------------------------------------+
| **Exportable Educational Products First Available for Distribution in |
| Report Year** *List five or fewer of the most important products. For |
| each item, limit the response to five lines summarizing content,      |
| target audience, format, and product evaluation plan and results.     |
| **Include educational products developed in previous years ONLY if    |
| this is the [first year]{.underline} they have been available for     |
| distribution.***                                                      |
|                                                                       |
| -   VAPSHCS GRECC, in concert with other GRECC personnel, began a     |
|     multi-site program to evaluate cognitive screening in primary     |
|     care settings. As of Fall 2006, VAPSHCS GRECC has designed and    |
|     implemented a needs assessment survey assessing current practices |
|     and protocols across the VISN, as well as barriers to screening   |
|     and perceived logistical needs. VAPSHCS GRECC is in the process   |
|     of collaborating with the St. Louis, Minneapolis, and Boston area |
|     GRECCs to design, implement, and evaluate a novel,                |
|     empirically-driven cognitive impairment screening protocol.       |
|                                                                       |
| -   The VAPSHCS GRECC website is now on-line and offers access to a   |
|     number of education-related materials, including streaming video  |
|     of the VTEL lectures previously only offered to the VISN. The     |
|     website also offers links to other area, regional, and national   |
|     resources and connects users to current research, educational,    |
|     and clinical services                                             |
+-----------------------------------------------------------------------+
| **7. CLINICAL DEMONSTRATION PROJECTS**                                |
+-----------------------------------------------------------------------+
| **NOTE:** A clinical demonstration [program]{.underline} is defined   |
| as:                                                                   |
|                                                                       |
| -   an ongoing, clinical, cooperative collaboration between the GRECC |
|     and host VA medical center;                                       |
|                                                                       |
| -   that carries out and evaluates assessment strategies, management  |
|     approaches and/or specialized investigations                      |
|                                                                       |
| -   of a targeted or focused group of elderly patients                |
|                                                                       |
| -   with the intention that findings will be disseminated for the     |
|     advancement of the field.                                         |
|                                                                       |
| A clinical demonstration program is comprised of one or more clinical |
| demonstration [projects]{.underline}, each of which is defined as     |
|                                                                       |
| -   a set of one or more clinical activities                          |
|                                                                       |
| -   integrated and coordinated under a specified protocol             |
|                                                                       |
| -   designed to permit evaluation(s) of processes and/or outcomes.    |
|                                                                       |
| Evaluation of a clinical demonstration program may be a comprehensive |
| assessment of the activity and/or the clinical outcomes.              |
| Alternatively, evaluation may concentrate on a prioritized and        |
| feasible set of more focused or specific, project-related questions,  |
| e.g. related to improved diagnosis, quality of care, patient          |
| satisfaction, drug compliance, functional status, etc.  Ongoing and   |
| subsequent modifications of the care model may also be evaluated as   |
| may be the practicability and outcomes of exporting new clinical      |
| models or variations of models to general care settings and/or        |
| smaller, more resource-limited VA medical centers or outpatient       |
| facilities.                                                           |
+-----------------------------------------------------------------------+
| a.  **Clinical Demonstration Projects Underway in Report Year***:     |
|     list **all** GRECC Clinical Demonstration Projects underway. For  |
|     each item, indicate whether [N]{.underline}ew or                  |
|     [O]{.underline}ngoing in Report Year. You may include up to five  |
|     lines of descriptive text for each Project.\                      |
|     *                                                                 |
|                                                                       |
| > **NOTE:** The number of Projects listed should be equal to the      |
| > number of Clinical Demonstration Projects you have listed and named |
| > in the GRECC Electronic Database.                                   |
|                                                                       |
| -   **[GRECC Osteoporosis/Andrology/Renal Stones                      |
|     Clinic]{.underline}.** This is a multi-disciplinary (geriatric    |
|     medicine, endocrinology and nephrology) directed by the GRECC     |
|     AD/C to evaluate and treat osteoporosis and other metabolic bone  |
|     diseases; male hypogonadism and erectile dysfunction; and         |
|     recurrent nephrolithiasis. Status: [O]{.underline}ngoing.         |
|                                                                       |
| -   **[GRECC Clinic]{.underline}.** This is a multi-disciplinary      |
|     (geriatric medicine, geriatric psychiatry, social work, pharmacy, |
|     and geriatric medicine and psychiatry fellows) geriatric medicine |
|     primary care and geriatric psychiatry referral clinic directed by |
|     the GRECC AD/C to care for complex elderly patients with          |
|     undiagnosed and/or severe psychiatric disorders (primarily        |
|     dementia and depression) who also have multiple medical           |
|     co-morbidities and who can not be cared for effectively in        |
|     general internal medicine clinic. Status: [O]{.underline}ngoing.  |
|                                                                       |
| -   **[Memory Disorders Clinic]{.underline}.** This is a              |
|     multi-disciplinary referral clinic directed by AD/EE to evaluate  |
|     and manage patients with dementia and other cognitive             |
|     dysfunction.                                                      |
|                                                                       |
| -   **[Neurogenetics Clinic]{.underline}.** This a referral and       |
|     research clinic directed by a GRECC Staff Physician, to evaluate  |
|     patients and families with neurodegenerative diseases (late-onset |
|     Alzheimer's disease, Huntington's disease, hereditary ataxia and  |
|     hereditary neuropathy), both clinically (phenotype) and           |
|     genetically (genotype). Status: [O]{.underline}ngoing.            |
|                                                                       |
| -   **[Palliative Care Program]{.underline}.** This is a newly        |
|     organized interdisciplinary program that is directed by a GEC     |
|     Staff Physician that provides consultative and case management    |
|     services and limited inpatient palliative care in newly renovated |
|     rooms on the Transitional Care Unit in order to relieve suffering |
|     and improve quality of life for terminal patients and their       |
|     families. A GRECC Staff Physician is involved in planning the     |
|     scope of palliative care program within the medical center.       |
|     Status: [N]{.underline}ew.                                        |
|                                                                       |
| ```{=html}                                                            |
| <!-- -->                                                              |
| ```                                                                   |
| -   **[Caregivers Support Group.]{.underline}** This is a program run |
|     by the GRECC Social Worker that provides a weekly support group   |
|     to caregivers of elderly patients. Status: [O]{.underline}ngoing. |
+-----------------------------------------------------------------------+
| b.  **Evaluation of Clinical Demonstration Projects:** *for each      |
|     GRECC Clinical Demonstration Project listed in 7a above,          |
|     summarize the evaluation activity. If no evaluation results are   |
|     available, be explicit as to the focus of the planned evaluation, |
|     and when it is anticipated to occur. If the project has been      |
|     completed during the Report Year, provide key findings and their  |
|     significance.*\                                                   |
|     \                                                                 |
|     **NOTE:** Do not list patient service use data here. Those data   |
|     are reported in the GRECC Electronic Database.                    |
|                                                                       |
| -   **[GRECC Osteoporosis/Andrology/Renal Stones                      |
|     Clinic]{.underline}.**                                            |
|                                                                       |
| ```{=html}                                                            |
| <!-- -->                                                              |
| ```                                                                   |
| -   Descriptive study of the adequacy or inadequacy of work up and    |
|     treatment for osteoporosis in patients with high-risk patients    |
|     with low-trauma hip fractures. This will serve as a baseline for  |
|     designing and testing strategies to improve the evaluation and    |
|     treatment of osteoporosis in an older population at high risk for |
|     subsequent fractures, morbidity and mortality. Status:            |
|     [O]{.underline}ngoing (analysis phase).                           |
|                                                                       |
| -   Development of clinical templates for the evaluation of patients  |
|     with osteoporosis, male hypogonadism and renal stones for primary |
|     care practitioners. These templates will be tested in the clinic  |
|     and modified as needed for use by primary care practitioners in   |
|     order to improve their work up of osteoporosis. Initial targets   |
|     for improvement will be the diagnosis of vitamin D deficiency and |
|     male hypogonadism in the older osteoporosis population. Status:   |
|     [O]{.underline}ngoing (development phase).                        |
|                                                                       |
| -   Testosterone Replacement And Dutasteride Effectiveness (TRADE)    |
|     Study. This is randomized, double-blind, single site study to     |
|     determine the effect of combined administration of                |
|     testosterone (T) plus the 5 alpha-reductase inhibitor,            |
|     dutasteride, versus testosterone replacement alone on prostate    |
|     size and lower urinary tract symptoms in older hypogonadal men    |
|     with mild to moderate benign prostatic hyperplasia. A sub-study   |
|     will assess the effects of T plus dutasteride versus T alone on   |
|     intra-prostatic T and dihydrotestosterone (DHT) concentrations,   |
|     histology and gene expression in epithelial and stromal cells     |
|     using laser capture microdissection and gene microarray analysis. |
|     This is an investigator-initiated study (PI, GRECC AD/C). Status: |
|     [O]{.underline}ngoing (recruitment phase).                        |
|                                                                       |
| ```{=html}                                                            |
| <!-- -->                                                              |
| ```                                                                   |
| -   **[GRECC Clinic]{.underline}.**                                   |
|                                                                       |
| ```{=html}                                                            |
| <!-- -->                                                              |
| ```                                                                   |
| -   Frailty assessment and management. This is an unfunded,           |
|     randomized pilot study to assess the value of directed            |
|     multi-disciplinary (physical therapy, geriatric medicine and      |
|     geriatric psychiatry) intervention versus usual care on mobility  |
|     disability (gait speed), as a risk factor for frailty in elderly  |
|     patients. Status: [O]{.underline}ngoing (development phase).      |
|                                                                       |
| -   Assessment of caregiver stress. This is an unfunded pilot study   |
|     to assess the impact of using the Screen for Caregiver Burden     |
|     (SCB) on the clinical care of elderly patients. Status:           |
|     [O]{.underline}ngoing (development phase).                        |
|                                                                       |
| -   Testosterone and Subsyndromal Depression Study. This is a         |
|     randomized, double-blind, placebo-controlled study comparing the  |
|     effect of testosterone replacement versus placebo on the severity |
|     of depression and quality of life in older men with mild or       |
|     subsyndromal depression. This is an investigator-initiated study  |
|     (PI, GRECC Staff Physician). Status: [O]{.underline}ngoing        |
|     (analysis phase).                                                 |
|                                                                       |
| ```{=html}                                                            |
| <!-- -->                                                              |
| ```                                                                   |
| -   **[Memory Disorders Clinic]{.underline}.**                        |
|                                                                       |
| ```{=html}                                                            |
| <!-- -->                                                              |
| ```                                                                   |
| -   Development and testing of guidelines for use of cognitive        |
|     enhancing medications in patients with dementia. Status:          |
|     [O]{.underline}ngoing (development phase).                        |
|                                                                       |
| -   Use of neuropsychological tests as predictors of driving          |
|     impairment in patients with Alzheimer's disease. Status:          |
|     [O]{.underline}ngoing (analysis phase).                           |
|                                                                       |
| -   Building on long-term memory as an approach to supportive group   |
|     therapy for patients with Alzheimer's disease. Status:            |
|     [O]{.underline}ngoing (analysis phase).                           |
|                                                                       |
| -   Funded clinical research studies by GRECC AD/EE. Status: ongoing  |
|     (recruitment phase):                                              |
|                                                                       |
| ```{=html}                                                            |
| <!-- -->                                                              |
| ```                                                                   |
| -   Therapeutic effects of rosiglitazone in patients with Alzheimer's |
|     disease.                                                          |
|                                                                       |
| -   Dose-response effects of intranasal insulin on memory in patients |
|     with Alzheimer's disease.                                         |
|                                                                       |
| -   Effects of daily intranasal insulin on cognition, functional      |
|     status and cerebral glucose metabolism in patients with           |
|     Alzheimer's disease.                                              |
|                                                                       |
| -   Effects of rosiglitazone on cognition, plasma amyloid and brain   |
|     atrophy in patients with mild cognitive impairment.               |
|                                                                       |
| ```{=html}                                                            |
| <!-- -->                                                              |
| ```                                                                   |
| -   **[Neurogenetics Clinic]{.underline}.**                           |
|                                                                       |
| ```{=html}                                                            |
| <!-- -->                                                              |
| ```                                                                   |
| -   No clinical demonstration projects are ongoing at present.        |
|                                                                       |
| ```{=html}                                                            |
| <!-- -->                                                              |
| ```                                                                   |
| -   **[Palliative Care Program]{.underline}.**                        |
|                                                                       |
| ```{=html}                                                            |
| <!-- -->                                                              |
| ```                                                                   |
| -   No clinical demonstration projects are ongoing at present.        |
|                                                                       |
| ```{=html}                                                            |
| <!-- -->                                                              |
| ```                                                                   |
| -   **[Caregivers Support Group.]{.underline}**                       |
|                                                                       |
| ```{=html}                                                            |
| <!-- -->                                                              |
| ```                                                                   |
| -   No clinical demonstration projects are ongoing at present.        |
+-----------------------------------------------------------------------+
| c.  **New Clinical Models developed at your GRECC that were exported  |
|     in the Report Year** *(list up to five examples, up to two lines  |
|     each; provide name of new clinical model, name of VA or non-VA    |
|     facility to which it was exported, and method of export, such as  |
|     "Falls Clinic protocol sent to [X]{.underline} VAMC"):*           |
|                                                                       |
| -                                                                     |
|                                                                       |
| **No clinical models were exported this report year.**                |
+-----------------------------------------------------------------------+
| **8. CONSULTATION AND OUTREACH**                                      |
+-----------------------------------------------------------------------+
| NOTE: **Consultation** = GRECC staff going to sites **[within host    |
| VAMC]{.underline}** or having those staff come to the GRECC, to       |
| assist in development of research, education or clinical programs at  |
| those sites. **Outreach** = GRECC staff going to **[non-host VAMC     |
| facilities]{.underline}** or having those staff come to the GRECC (in |
| person or by video or other technology) to assist in development of   |
| research, education or clinical programs at those sites.              |
+-----------------------------------------------------------------------+
| b.  **Current Year Activity Outcomes** *(list up to five examples, up |
|     to two lines each; summarize specific outcomes realized from      |
|     current year **consultation**, e.g., "Host VAMC instituted a      |
|     Falls Clinic after consultation from GRECC staff;" or             |
|     **outreach**, e.g., [X]{.underline} VAMC instituted a Falls       |
|     Clinic after GRECC outreach via series of videoconferences):*     |
|                                                                       |
| -   [Consultation,]{.underline} Dr Craft and the Memory Disorders     |
|     Clinic teamed with Dr Sharon Falzgraf of GEC to develop a         |
|     clinical education program for geriatric fellows and residents on |
|     the treatment and diagnosis of Memory Disorders.                  |
|                                                                       |
| -   The GRECC is providing in-service outreach to the CBOC's on       |
|     geriatric cognitive treatments and has sought to increase         |
|     consults from CBOC's to the Memory Disorders Clinic.              |
|                                                                       |
| -   GRECC Investigator Dr. Molly Shores and Geriatric Psychiatry      |
|     fellow Lucy Wang M.D. have teamed up with Marcella Pascually MD   |
|     to implement a prazocin research protocol in the GRECC Clinic.    |
+-----------------------------------------------------------------------+
| b.  **Previous Years' Activities Outcomes** *(list up to five         |
|     examples, up to two lines each; summarize specific outcomes       |
|     realized from previous years' [**consultation** to host           |
|     VAMC]{.underline} or [**outreach** to non-host                    |
|     facilities]{.underline}, where results were first realized in the |
|     current year.)*                                                   |
|                                                                       |
| -   **No outcomes to report this year**                               |
+-----------------------------------------------------------------------+