DRAFT

The 99th Meeting
September 26–27, 2006

CONTENTS

1. REVIEW OF APPLICATIONS
2. CALL TO ORDER
3. COMMENTS FROM RETIRING MEMBERS
4. REPORT: TASK FORCE ON MINORITY AGING RESEARCH
5. REPORT: WORKING GROUP ON PROGRAM
6. PRESENTATION: Friends of the National Institute on Aging
7. PRESENTATION: Geriatrics and Clinical Gerontology Program Review
8. PROGRAM HIGHLIGHTS
9. ADJOURNMENT
10. CERTIFICATION

Attachment A: Roster of the National Advisory Council on Aging
Attachment B: Director's Status Report

The 99th meeting of the National Advisory Council on Aging was convened on Tuesday, September 26, 2006, at 3 p.m. in Building 31, Conference Room 10, National Institutes of Health (NIH), Bethesda, MD. Dr. Richard J. Hodes, Director, National Institute on Aging (NIA), presided.

In accordance with the provisions of Public Law 92--463, the meeting was closed to the public on Tuesday, September 26, from 3 p.m. to 5 p.m. for the review, discussion, and evaluation of grant applications in accordance with the provisions set forth in Sections 552(b)(c)(4) and 552(b)(c)(6), Title 5, U.S. Code and Section 10(d) of Public Law 92--463.1 The meeting was open to the public on Wednesday, September 27, from 8 a.m. to 1:30 p.m.

Council Participants:
Dr. Elizabeth H. Blackburn
Dr. Melissa Brown
Dr. Kenneth V. Brummel-Smith
Dr. John T. Cacioppo
Dr. Linda P. Fried
Dr. Lawrence M. Friedman
Dr. Mary Ganguli
Dr. Alan M. Garber
Dr. Virginia M.-Y. Lee
Dr. Spero Manson
Dr. Terry L. Mills
Dr. John C. Morris
Dr. Gary B. Ruvkun (by telephone)
Dr. Gerald P. Schatten
Dr. Albert L. Siu
Dr. Mary E. Tinetti

Absent:
Dr. Carl Eisdorfer
Dr. Paul Greengard

Ex-officio Participants:
Dr. James Burris, Department of Veterans Affairs

The Council Roster, which gives titles, affiliations, and terms of appointment, is appended to these minutes as Attachment A.

In Addition to NIA Staff, Other Federal Employees Present:
Dr. Francois Boller, Center for Scientific Review, NIH
Dr. Gabriel Fosu, Center for Scientific Review, NIH
Dr. Claire Gutkin, Center for Scientific Review, NIH
Dr. Dana Plude, Center for Scientific Review, NIH
Dr. Anna Riley, Center for Scientific Review, NIH
Dr. Robert Weller, Center for Scientific Review, NIH

Members of the Public Present:
Dr. Gerald Berenson, Tulane University
Ms. Cynthia Farrell, Alliance for Aging Research
Ms. Christy Gilmour, American Academy of Orthopaedic Surgeons
Dr. Rose Maria Li, Rose Li and Associates, Inc.
Ms. Christine Maisano, Rose Li and Associates, Inc.
Mr. Daniel Perry, Alliance for Aging Research and Friends of NIA
Ms. Amy Pollick, Association for Psychological Science
Dr. James P. Smith, RAND Corporation
Dr. Mone Zaidi, Mount Sinai School of Medicine

I. REVIEW OF APPLICATIONS

This portion of the meeting was closed to the public, in accordance with the determination that it concerned matters exempt from mandatory disclosure under Sections 552(b)(c)(4) and 552(b)(c)(6), Title 5, U.S. Code and Section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. Appendix).2

A total of 1028 applications requesting $964,936,216 for all years underwent initial review. The Council recommended 549 awards for a total of $617,287,438 for all years. The actual funding of the awards recommended is determined by the availability of funds, percentile ranks, priority scores, and program relevance.

II. CALL TO ORDER

Dr. Hodes welcomed members to the open session of the National Advisory Council on Aging and called the meeting to order at 8:10 a.m. on Wednesday, September 27, 2006.

A. Director's Status Report

Dr. Hodes began his report by reviewing the evolution of NIH reauthorization. From 1944--1985, Congress passed bills to amend missions of existing Institutes and Centers (ICs) or create new ICs. The first omnibus reauthorization of the NIH occurred in 1985. Following a second omnibus reauthorization in 1993, the authorization process was subsumed by appropriations laws up through 2004. In the post-doubling period (2004--2006), lawmakers focused on accountability and oversight for the NIH. Between 2002 and 2006, the U.S. House of Representatives Committee on Energy and Commerce Subcommittee on Health held a number of hearings focused on specific topic areas related to the NIH, including investing in research to prevent and cure disease, moving research from bench to bedside, balancing the priority-setting process, improving portfolio management, improving NIH management and operations, and legislation to reauthorize the NIH. During this process, a number of preliminary ideas were discussed to restructure the NIH, establish a Common Fund for trans-NIH research, and establish a uniform electronic grants and activities coding system. These efforts culminated in the House passage of H.R. 6164, the NIH Reform Act of 2006.

H.R. 6164 authorizes a yearly 5-percent increase in appropriation over the previous fiscal year (FY) for FY 2007--FY 2009, beginning with $29,747,874,000 in FY 2007, and makes increases in IC appropriations contingent upon an annual reporting requirement on multi-IC collaborations (although the NIH Director is authorized to waive this requirement). It also increases the trans-NIH Common Fund, which was about 1.2 percent of the NIH budget in FY 2006, to 5 percent of the NIH budget in FY 2007, 7.5 percent in FY 2008, and 10 percent in FY 2009. To reach the 5-percent set-aside, 50 percent of the newly appropriated funding increase will supplement the Common Fund starting in FY 2007. H.R. 6164 limits the number of ICs to the current 27 and creates the Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI), to be supported by the Common Fund. It calls for the establishment of a Scientific Management Review Board to review NIH structure and propose changes every 7 years and the Council of Councils (previously called Advisory Council) to advise the NIH Director on policies and activities of DPCSI. It also includes new language for conflict-of-interest reporting, maximization of investigator-initiated research, tissue specimen tracking, and minority and health disparities reporting.

In response to a question posed by a Council member, Dr. Hodes explained that a difference between the appropriated amount and authorized budget can occur. However, if Congressional members object to the appropriations amount exceeding the authorized budget, they may call a point of order.

Dr. Zerhouni's current proposal calls for the Common Fund to reach 1.7 percent of the overall NIH budget by FY 2008, with each IC transferring this fraction of its appropriation to constitute the Fund. Increases in this percentage would be considered when the NIH budget increases at a rate that exceeds biomedical inflation. The House proposed reauthorizing measure, H.R. 6164, would authorize total NIH appropriations to increase as much as 5 percent each year through FY 2009 with 50 percent of this increase going towards the Common Fund. This would result in the Common Fund increasing to 5 percent of the NIH Budget by FY 2009. As you know, the President's FY2007 budget did not propose an increase for FY 2007 and later fiscal years.

Dr. Hodes indicated that Representative Joe Barton (R--Texas) was initially the driving force behind the bill, but now there is fairly broad support for the bill in the House Committee on Energy and Commerce Subcommittee on Health and the House of Representatives as a whole. Thus, a change in Committee leadership is unlikely to have much effect on the bill. The most critical factor in the future of the bill is whether it is taken up by the Senate.

B. Announcements

Dr. Elizabeth Blackburn was congratulated by Dr. Hodes and Council members on her receipt of the 2006 Albert Lasker Medical Research Award. The award was given to Dr. Blackburn and her colleagues for their prediction and discovery of telomerase.

A compilation of media coverage since the last Council meeting was circulated among Council members for their review.

C. Future Meeting Dates

January 30--31, 2007 (Tuesday and Wednesday)
May 15--16, 2007 (Tuesday and Wednesday)
September 25--26, 2007 (Tuesday and Wednesday)

D. Consideration of the Minutes of Last Meeting

The minutes of the May 2006 meeting were considered. A motion was made, seconded, and passed to approve the minutes.

III. COMMENTS FROM RETIRING MEMBERS

Each retiring Council member was presented with a plaque and a letter signed by Department of Health and Human Services Secretary Michael Leavitt and was invited to make comments.

Dr. Hodes commended Dr. Elizabeth Blackburn for the wisdom she has brought to Council, not only in areas of basic science but also in the ethics and conduct of science. Dr. Blackburn expressed her gratitude at the opportunity to serve on Council with its outstanding members. She described the NIA as a national treasure, indicating that the range and importance of its mission coupled with its extraordinary staff contribute to its prominence among Institutes.

Dr. Hodes recognized the contributions of Dr. Melissa Brown, particularly her constant questioning of how NIA-supported science will translate to the community as well as the nature of research priorities. Dr. Brown thanked everyone for the honor and privilege of serving on Council, expressing the hope that she can continue to provide guidance beyond her tenure as a Council member.

Dr. Hodes acknowledged Dr. Linda Fried for her dedication of time and effort to the Council, demonstrated in part by her service as Chair of the Working Group on Program. Dr. Fried expressed her gratitude for the honor of serving as a Council member. She noted the evolution of aging research into a complex science that is consonant with the priorities of the NIH Roadmap, and stated that she looks forward to the development of the NIA's new strategic plan.

Finally, Dr. Hodes honored Dr. Spero Manson for the unique scientific expertise that he has brought to Council deliberations and for his leadership as head of the Task Force on Minority Aging Research. Dr. Manson appreciated his experience on Council, which provides a forum for members to share their experiences with the community. He wished the remaining Council members a successful journey in the years ahead and expressed pride at being associated with the NIA.

IV. REPORT: Task Force on Minority Aging Research

Dr. Spero Manson reported on the work of the Task Force on Minority Aging Research, which seeks to ensure that minority aging research remains a vital part of the Institute's strategic plan. Currently, the NIA has research, infrastructure, and public education goals to address health disparities. However, Task Force members have expressed concern that some researchers include minority populations in their sampling design simply to fulfill a requirement. The Task Force has concluded that inclusion of minority groups in research is critical to the mission of science. Discussion at their most recent meeting focused on outreach, recruitment, and retention of health disparity populations in aging research.

The Task Force identified several critical needs that must be met in order to move minority aging research forward:

• Development of evidence-based recruitment and retention models and theoretical frameworks;
• Evaluation of minority research recruitment and retention plans and dissemination of successful implementation plans to the research community;
• Increase in the number of minority and diverse investigators; and
• Reconsideration of exclusion based on multiple morbidities, a criterion that may inhibit minority participation.

The Task Force is considering several measures to fulfill the need for evaluation and dissemination of successful research recruitment plans. One is development of a Web-based toolkit that will provide in one accessible location examples of successful retention and recruitment plans implemented by NIA investigators. A potential means for developing this toolkit is a research conference grant that brings together NIA investigators working in minority aging research to develop guidelines that will inform the toolkit.

The other measure being considered by the Task Force is using the Evaluation Express Award mechanism to support formalized, systematic evaluation of successful efforts in recruitment and retention of health disparity populations in aging research. This award, administered by the NIH Office of Portfolio Analysis and Strategic Initiatives, provides a fast and efficient method to obtain up to $50,000 in funding for eligible evaluation efforts. The proposed evaluation would examine the influence of study design and incentives used on recruitment and retention productivity in health disparity populations in NIA clinical studies from 2000--2005. The Task Force envisioned multiple uses for the results generated from this award: Summary report and recommendations posted on the Research Information page of the NIA Web site, development and collaboration with the NIA Office of Communications and Public Liaison, journal publications, workshops held coincident with the Resource Centers for Minority Aging Research conferences, and presentation at the 2007 meeting of the Gerontological Society of America.

V. REPORT: Working Group on Program

Dr. Linda Fried reported that the September 26, 2006, meeting of the Working Group on Program (WGOP) featured continued discussion, initiated over a year ago, on Council's advisory role. The WGOP deliberated on how Council can harness the unique expertise of its members to provide more effective advice to the NIA regarding its overall plans and initiatives. Another topic of discussion was whether Council could assist the NIA to partner with key organizations that will strengthen the Institute in its mission and improve public education about the value of aging research. Finally, the WGOP considered Council member interest in evaluating the success of innovative programs established by NIA leadership to improve the recruitment of physician-investigators in aging research.

To facilitate the WGOP's discussion, Ms. Kathie Reed from the NIA Office of Planning, Analysis and International Activities presented the NIA's processes of initiative development, priority setting, and funding decision-making, simultaneously educating WGOP members on Council's role in these processes. She also discussed the development in the upcoming year of a new NIA strategic plan. The development timeline has been revised in response to WGOP's expressed desire to have early and active involvement in formation of the strategic plan. Council members will be invited to provide input on the strategic plan before the January 2007 meeting, at which time a draft will be presented to Council for further comment. Dr. Fried noted that Council members outside of the WGOP have expressed excitement about contributing to the new strategic plan. Thus, the WGOP broadened its original proposal to create a task force focused on providing advice to the NIA on overall plans and initiatives to include all Council members in this task, with the WGOP serving as a vehicle for discussion.

The WGOP also discussed a proposal to create a task force that will evaluate the physician-investigator recruitment programs, identify progress, and determine where improvements are needed. Dr. Fried suggested that an evaluation begin with the Geriatrics and Clinical Gerontology Program. Proposed task force members include Drs. Eisdorfer, Friedman, Ganguli, Mills, Schatten, and Siu. The establishment of the task force was approved by Council voice vote. Other Council members may join the task force if interested.

Finally, Dr. Fried indicated that another task force was proposed to focus on Council advocacy with key partners in an effort to shape overall policy for aging programs as they intersect with the mission of the NIA. However, the WGOP decided to postpone a decision about creating such a task force until their next meeting, after hearing today's presentation from the Friends of the NIA.

A. RFA Concept Clearance

One request for RFA concept clearance was recommended for approval by the WGOP and approved unanimously by Council voice vote.

National Long-Term Care Survey
Ms. Georgeanne Patmios presented for concept clearance a proposed RFA to continue the National Long-Term Care Survey (NLTCS) under the cooperative agreement mechanism. This 24-year-old survey is a primary resource for studying changes in elderly health and functional status and for tracking health expenditures, Medicare service use, and the availability of personal, family, and community resources for caregiving. The NLTCS monitoring board and the broader research community have commented that the NLTCS has remained virtually unchanged since inception and that few researchers external to the core NLTCS group have used the data. Therefore, the NIA Behavioral and Social Research (BSR) Program asked the National Academy of Sciences (NAS) to hold two expert meetings (in October 2005 and February 2006) to discuss different options for the future of the survey. The consensus of these meetings was that the NLTCS is a unique and valuable resource for understanding the disability and functioning of America's elderly population; thus, the survey should be sustained, but with a significant redesign to enhance its research value. BSR obtained additional input from the September 2006 NAS workshop on identifying new interventions to extend the disability decline at a population level and the September 2006 meeting of the Committee on Data Priorities for Behavioral and Social Research on Aging,

Informed by these deliberations, the proposed RFA will have two goals: (1) To field a 2009 wave of the NLTCS, collecting the most critical updates needed to preserve the rich trend data and to make the data publicly available; and (2) to invite applications for a redesign of the NLTCS beyond the 2009 wave. The awardee will not be required to redesign the survey before the 2009 wave, but applications proposing to do so would be considered. Although the NIA does not plan to issue another RFA to support a subsequent data collection beyond the 2009 wave, a continuation application and/or competing supplement from the awardee would be considered.

VI. PRESENTATION: Friends of the National Institute on Aging

Mr. Daniel Perry is Chair of the Friends of the NIA (FoNIA), a coalition formed within the past year of some 50 organizations from academia and the nonprofit community. He is also Director of the Alliance for Aging Research, one of the FoNIA member organizations. FoNIA member organizations conduct, fund, or advocate for scientific efforts to improve the health and quality of life for aging Americans.

Mr. Perry began by describing some messages that FoNIA carries to the public on behalf of NIA. The audience consists primarily of those interested broadly in healthcare and science, including business groups, policymakers, members of Congress and their staff, journalists, and policymakers. Although it is thought that the current generation is the first to think boldly about vitality and activity long past traditional retirement age, this concept is actually rooted in post--World War II optimism about aging. With the aging of the Baby Boomers, a more robust idea of aging has begun to eclipse earlier notions of reduced life capacity. It is important to note the underlying fascination with the science of aging as demonstrated by popular media, which is replete with articles on the causes of aging and ways to slow it.

Many popular images of aging today do not address the most pressing issues of our aging society; specifically, the cost and impact of people living longer and their increased vulnerability to a host of age-related chronic diseases, comorbidities, and polypharmacy. A current area of political debate centers on the rising cost of healthcare and the economic burden of disease. Care for people with chronic disease consumes 78 percent of healthcare spending. Two-thirds of people age 65 and over have two or more chronic conditions. The average 75-year-old has three chronic conditions and is on five medications.

According to a study by the RAND Corporation, the cost of care for a person who remains independent is approximately $5,500. This amount quadruples if the individual needs help with daily activities, and if the individual's loss of independence leads to a nursing home admission, the cost doubles again to $41,040. These figures aggregate to a $30-billion per year hidden cost from loss of independence. When these disturbing trends are shared with the public, Mr. Perry has found that they are very open to the idea of aging research as the primary way to alter this trajectory.

Arguments for aging research are strengthened by the universality of the human experience with aging, the certainty of larger numbers of older people in the future, and the challenges that the population will face from a host of chronic health problems and disabilities that often attend older aged individuals. The countervailing difficulties inherent in advocating for aging research include its complexity; divided opinion even among experts as to the nature of aging, health, and age-related disease; a pervasive ageism in American society that devalues the lives of older people; the absence of biomarkers to determine success of interventions aimed at modifying the course of aging; and competition for public attention with what are perceived as more immediate national crises. These realities, coupled with the trend of decreased funding for aging research and NIH research in general, underscore the fact that advocates need to do a better job on behalf of aging research.

The FoNIA seeks to provide a link between NIA and the external aging advocacy community. In 2006, FoNIA activities included testifying before the U.S. House of Representatives and Senate appropriations committees to increase NIH and NIA funding and endorsing the Markey Amendment for a 5-percent increase in the NIH reauthorization. One idea for the future is to facilitate a regular national conference call in which either the NIA Director or designee provides a status report; the FoNIA could invite a broad group of attendees, including Congressional staff. In addition, a future goal is to build the FoNIA into a larger coalition with a greater impact, and it is anticipated that Council could recommend other organizations for inclusion. Mr. Perry emphasized that the FoNIA is not just a legislative lobbying group; rather, its mission is to carry the message of the value of aging research to the broader community, and he invited Council members to discuss how they can best contribute to this mission.

Discussion focused on FoNIA operations and how Council and the NIA can work together to advance their shared interests in aging research. Mr. Perry welcomed input from Council members on the activities they deem most appropriate for their involvement. One member suggested that since efforts to increase appropriations for NIA-funded research may not be fruitful in the current budgetary climate, FoNIA could help the NIA with making more effective use of the funds its does have. In particular, it is increasingly difficult for investigators to recruit older adults for clinical trials research, and small-scale campaigns to increase public awareness and trust and encourage research participation are resource intensive. FoNIA could partner with media organizations and community advocacy groups to produce a public service message that will emphasize the need for public participation in research. Mr. Perry affirmed that this is a critical need and stated that he intends to follow up this suggestion by researching what other groups are already doing in this area. One Council member suggested that another message for the FoNIA to carry is the economic benefits of an aging society, which is often forgotten in concerns about the costs of aging. Mr. Perry agreed that this is an important message, although the presentation of it may differ depending on the audience. He noted that one challenge is identifying an inspiring messenger who can represent aging research and capture the public imagination.

Another member noted that aging advocates do not have a "catch phrase" for the mission of aging research, and this is partly due to a lack of consensus about whether aging research should be considered disease-oriented research or general medical science. Mr. Perry acknowledged this tension, which the Alliance for Aging Research recently addressed at a meeting they hosted on Capitol Hill. Invited speakers framed investment in aging research as the "longevity dividend." Rather than addressing diseases in research "silos," they argued, aging research seeks to understand the biological underpinnings of aging, which will advance the understanding of major chronic diseases such as diabetes, cardiovascular disease, cancer, and neurological disease. Mr. Perry stated that the meeting proceedings are available in DVD format on the Alliance for Aging Research Web site at www.agingresearch.org.

In response to a question, Ms. Cynthia Farrell, government relations director for the Alliance, explained to Council that during the House Committee on Energy and Commerce consideration of the NIH Reform Act of 2006, Congressman Ed Markey (D-MA) offered an amendment intended to increase the authorization levels contained in the bill from 5 percent to 5 percent plus the rate of biomedical inflation between FY 2007 and 2009. Despite an endorsement from FoNIA, the amendment failed to garner enough support among committee members. Ms. Farrell also noted that FoNIA has a favorable view of the establishment of a Common Fund for trans-NIH research activities because NIA applications are likely to satisfy the main requirements for consideration by being collaborative in nature and addressing emerging public health challenges.

Discussion turned to expanding coalition membership and facilitating appropriate involvement for current and former Council members in FoNIA advocacy efforts. FoNIA does not differ fundamentally from advocacy groups that have formed around other Institutes. However, Mr. Perry believes that the FoNIA has the potential for mobilizing a larger coalition of organizations representing specific diseases, women, and the older population in general, thus bringing a message that applies to a broader spectrum of society. To be effective in this vision, the FoNIA must forge a strong bond with the staff and leadership of NIA, particularly Council in its advisory role to the Institute.

VII. REPORT: Geriatrics and Clinical Gerontology Program Review

Dr. Mary Tinetti briefly summarized the recent activities undertaken as part of the Geriatric and Clinical Gerontology Program review. On September 25, 2006, former and current Council members met with Program staff and other NIA staff members who presented the goals of the Program to the reviewers and facilitated discussion. Afterward, the reviewers met to summarize their discussion and develop overall recommendations for the Program. Between now and the next Council meeting, the reviewers will complete the written report, which will contain structural and content recommendations. Dr. Tinetti will present highlights from that report to the Council at the January 2007 meeting.

VIII. PROGRAM HIGHLIGHTS

A. Biology of Aging: New Insights in Understanding Osteoporosis

Dr. Mone Zaidi, an endocrinologist and Professor of Medicine, Mount Sinai School of Medicine, presented recent research results related to osteoporosis, highlighting pathways for the pathogenesis of this disease.

Osteoporosis is a crippling bone disease that affects 44 million American women. Its incidence increases with age and will likely escalate as the numbers of elderly men and women increase over the next decade. The incidence of osteoporotic fractures in postmenopausal women far outweighs the combined incidence of breast cancer, heart disease, and stroke in the same population and is increasingly common in men. Despite the frequency of the disease and the fact that nearly $19 billion is spent in related health costs, the current standard of care for osteoporosis is dismal. Greater understanding of the pathophysiology of the disease has led to discovery of new targets for therapeutic intervention, and new therapeutics are expected to reach the market within the next decade.

It is now known that very early in the disease process, well before clinically observable changes in bone density, significant architectural and micro-architectural deterioration leads to greater bone fragility and ultimately increased fractures. The clinical implication is that drugs can stabilize the micro-architecture, thereby significantly reducing the risk of fracture. The key differences between bone loss in men and women are that men begin life with a higher bone mass and women have accelerated bone loss that starts over the menopausal transition, which means that they reach this potentially fractured threshold much earlier than men.

Postmenopausal osteoporosis has been thought to arise from low estrogen levels, an archetypal explanation that Dr. Zaidi and colleagues have challenged on the basis of their studies with genetically manipulated mouse models. They thus revisited the pathophysiology of postmenopausal bone loss that results from estrogen deficiency and the osteoporosis found in hyperthyroidism that is thought to result from elevated thyroid hormone levels. In these states, pituitary hormones, namely follicle stimulating hormone (FSH) and thyroid stimulating hormone (TSH), are reciprocally regulated by feedback. Thus, estrogenic feedback during the menopause causes an elevation of FSH, and feedback by elevated thyroid hormones lowers TSH, often to undetectable levels, in hyperthyroidism.

Evaluation of the direct actions of FSH and TSH on bone and bone cells suggests that elevated FSH and lowered TSH levels contribute to the bone loss in hypogonadal and thyrotoxic states. Haploinsufficiency of FSH and the TSH receptor in heterozygotic mice, which have conserved ovarian and thyroid function, display high and low bone mass, respectively. This suggests that the actions of FSH and TSH on the skeleton are independent of the hormones they release from the ovary and thyroid gland, respectively. Both FSH and TSH receptors have been identified on osteoclasts, while only TSH receptors were detected on mature osteoblasts. The integrity and strength of bones depends on balancing bone resorption or erosion by osteoclasts against bone formation by osteoblasts. Activation of the TSH receptor causes a dramatic reduction in osteoclast formation, bone resorption, and osteoclast survival through the inactivation of MAP kinase and NF-kB signaling. The reverse occurs with FSH in both mouse and human osteoclast cultures. Epidemiologic studies reveal a close correlation between fracture risk and serum TSH levels in hyperthyroid patients. Furthermore, patients with TSH receptor mutations have bone loss despite being rendered euthyroid with thyroxine therapy. Recombinant human TSH inhibits bone turnover in postmenopausal women. Clinical data implicating elevated FSH in the genesis of postmenopausal osteoporosis are just beginning to appear. Strong correlations nonetheless exist between bone mass and FSH rather than estrogen levels across the menopausal transition. With normal or absent FSH levels, bone loss is fairly mild, whereas with high FSH levels, bone loss can be increased. The Study of Women's Health across the Nation clearly showed that FSH levels, rather than the estrogen levels in the circulation, correlated with markers of bone remodeling and bone mass in the early postmenopausal woman. Together, these studies implicate anterior pituitary hormones in the direct control of bone cell function in skeletal health and disease.

These studies identify several new therapeutic targets for osteoporosis. Recombinant human TSH could be used as a therapeutic. Oophorectomy-induced bone loss in animals was reversed with estrogen and parathyroid hormone, which was essentially the effect of TSH. In an early study in humans, a single injection of TSH profoundly decreased the marker of bone resorption. There is also potential for development of an FSH blocker. The question driving development of this therapeutic is whether an FSH blocker can prevent early postmenopausal bone loss without further impairing ovarian function, thus allowing the use of low-dose estrogen as opposed to high-dose estrogen for postmenopausal symptoms. There is also the potential that blocking FSH could prevent other postmenopausal symptoms.

In response to questions, Dr. Zaidi explained that the rapidity by which hormones decline is reflected in the rapidity by which bone is lost in humans. Surgical oophorectomy leads to acute, rapid, and severe bone loss, with fractures in about 6 months without any change in bone density. Estrogen supplementation has been shown to decrease FSH in oophorectomized mice or women, which may explain why estrogen supplementation is variably successful in decreasing bone loss in women. Women who have been influenced by the Women's Health Initiative study results to stop estrogen therapy have experienced precipitous loss of bone, although it is less severe as compared to the loss from use of aromatase inhibitors (which do not block estrogen production in the ovaries but instead block other tissues from producing estrogens, thus reducing the amount of estrogen in the body), which is in turn less acute than the loss following oophorectomy. Dr. Zaidi also reported that Depo-Provera, a contraceptive that stops ovaries from releasing eggs, has been found to be associated with bone density loss but the loss appears to be largely reversible. It is not clear whether women who undergo infertility treatments where they are exposed to much higher FSH levels experience a form of transient osteoporosis.

One study has found that statins enhance new bone formation in vitro and in rodents (Science. 1999; 286:1946-1949), but a large-scale clinical trial is needed to demonstrate the relationship with greater certainty. Questions from Council members suggested interest in considering effects from vitamin K, which is required for collagen synthesis, and from ApoE4.

Dr. Zaidi reiterated that for osteoporosis to occur, osteoclastic activity must outweigh osteoblastic bone formation. He described two completely distinct pathophysiological scenarios. The first is that after menopause, more osteoclasts are being produced and their heightened activity is such that the osteoblasts are unable to "catch up." This is what is termed in the literature as "high turnover osteoporosis." The second form of osteoporosis occurs as a function of getting older; the osteoblasts slow down so that for a given level of osteoclastic resorption, the dysfunctionality of the osteoblast leads to net bone loss. Thus, one can target osteoporosis either by reducing the formation of osteoclasts, such as with Fosamax or hormone replacement therapy, or stimulate the formation of bone by the osteoblasts. The only drug that has been approved for use to increase osteoblasts in the United States, and in fact, in any part of the world, is parathyroid hormone. Individuals with high levels of parathyroid hormone lose bone. However, if the same hormone is injected daily, it activates the osteoblasts, which results in profound effects on bone density and substantially reduces fractures. However, the treatment is expensive, and daily injections can be problematic.

Essentially, there are currently four treatment approaches for osteoporosis: (1) Weight-bearing exercise, which has been shown in some clinical studies to be a powerful anabolic agent; (2) calcium; (3) vitamin D, which is absolutely necessary; and (4) bisphosphonates. Unfortunately, exercise by itself does not overcome the rapidity of postmenopausal bone loss.

Other questions highlighted the need for additional research on postmenopausal changes in glycosylation and changes in the phosphorylation status of the FSH receptor, therapeutic modulation of FSH levels, and the role of FSH levels in males.

B. Behavioral and Social Research: Disease and Disadvantage in the United States and in England

Dr. James Smith is a senior economist at RAND Corporation and a two-time NIA MERIT [Method to Extend Research in Time] awardee. Dr. Smith presented findings from his research on the relative heath status of older individuals in England and the United States, especially how their health status varies by important indicators of socioeconomic position. It is based in part on two papers (JAMA. 2006;295:2037-2045; and NBER, forthcoming). The study examined a number of health outcome measures: (1) Self-reported morbidity, concentrated on seven major diseases; (2) self-reported general health status; (3) biological indicators of disease; and (4) mortality and life expectancy.

The research examined representative samples of residents ages 55--64 in both countries. The data are based on the American Health and Retirement Study (HRS) and the English Longitudinal Study of Ageing (ELSA), which were designed to have directly comparable measures of health, income, and education. Self-reported prevalence rates of several chronic diseases related to diabetes and heart disease, adjusted for age and health behavior risk factors, were compared across the two countries and across education and income classes within each country. This analysis was supplemented by samples of those aged 40--70 from the 1999--2002 waves of the National Health and Nutrition Examination Survey (NHANES) and the 2003 wave of the Health Survey for England (HSE). These surveys contain extensive and comparable biological disease markers on respondents, which were used to determine whether differential propensities to report illness can explain health differences. To ensure that health differences were not solely due to health issues in the African-American or Latino populations in the United States, the analysis was limited to non-Hispanic Whites in both countries.

The American population in late middle age was found to be less healthy than the equivalent British population for diabetes, hypertension, heart disease, myocardial infarction, stroke, lung disease, and cancer. Within each country, there existed a pronounced negative socioeconomic status (SES) gradient with self-reported disease so that health disparities were largest at the bottom of the education or income variants of the SES hierarchy. This conclusion was generally robust. A standard set of behavioral risk factors, including smoking, obesity, and alcoholic intake explained very little of these health differences; nor were the differences between countries, or across SES groups within each country, due to biases in self-reported disease--biological markers of disease exhibited the same patterns. Based on self-reported illnesses and biological markers of disease, Americans were much less healthy than their English counterparts and these differences existed at all points of the SES distribution. To illustrate, among those aged 55--64 years, diabetes prevalence was twice as high in the United States and only one-fifth of this difference can be explained by a common set of risk factors. Similarly, among middle age adults, mean levels of C-reactive protein were 20 percent higher in the United States compared with England, and mean high-density lipoprotein (HDL) cholesterol levels were 14 percent lower. These differences were not solely driven by the bottom of the SES distribution; in many diseases the top of the SES distribution was less healthy in the United States as well.

Dr. Smith speculated about possible reasons for these health differences. He noted that although at age 55 life expectancy for males is exactly the same in the United States as in England, age-specific death rates are 20 to 30 percent higher for Americans in their 50s and early 60s compared to their English counterparts, but this disadvantage switches somewhere around age 65, when the English age-specific mortality rates exceed those of Americans.

He dismissed a number of explanations as unlikely, including standard behavioral risk factors, self-reported morbidity problems, higher income inequality in the United States, or non-access to health insurance (94 percent of the U.S. sample had insurance coverage). Perhaps more important is health insurance coverage as a child, since that would determine how childhood illnesses and diseases were treated. However, this information is difficult to obtain as it is unlikely that people will remember whether they had health insurance as a child.

More promising explanations might include, in part, differential screening and differential fatality rates; health effects on income, which appear to be stronger in the United States; stress associated with higher income; less attention to prevention; and less exercise. Dr. Smith considered the exclusion of exercise (for lack of data) to be a major limitation that needs to be rectified.

A full explanation is likely to involve multiple factors, including earlier life influences. Dr. Smith stated that most of his work looks at the later-life consequences of childhood events, particularly economic consequences. He contended that people can recall childhood illnesses remarkably well. These data are currently being imported into the HRS and ELSA. One Council member offered that there needs to be communication between bench researchers and survey researchers so that insights into in utero and early childhood influences can inform such work. Dr. Richard Suzman added that efforts are underway to mine British cohort data and to explore relating U.S. cohorts that start in early childhood to survey cohorts that began in later life (e.g., age 50+).

A number of activities are underway, including modeling disease incidence in both countries; incorporating a larger set of behavioral risk factors and onset dates; looking more closely at specific diseases--starting with diabetes, and then heart disease and cancer; investigating the legacy of childhood diseases in the two countries; examining the social determinants of health, such as where people live and work over their lifetimes; and unraveling the morbidity-mortality puzzle; i.e., the greater incident mortality in England. Efforts also are underway to harmonize laboratory reference standards between NHANES and the HSE.

C. Neuroscience and Neuropsychology of Aging: Alzheimer's Disease and Mild Cognitive Impairment--Time To Revise Criteria?

Council Member Dr. John Morris is the Harvey A. and Dorismae Hacker Friedman Professor of Neurology as well as Director and Principal Investigator of the Alzheimer's Disease Research Center (ADRC) at Washington University School of Medicine. In the latter capacity, he recently led the effort to create a uniform data set to promote collaborative research by standardizing the clinical and cognitive data that all 29 ADRCs send to the National Alzheimer's Coordinating Center. Of note, the data set focuses on a prodromal stage of Alzheimer's Disease (AD), termed mild cognitive impairment (MCI), in comparison with normal aging. This focus is commensurate with the trend in ADRCs as well as within another large NIA-sponsored consortium, the AD Neuroimaging Initiative.

Current clinical diagnostic criteria for AD were developed more than two decades ago. New knowledge about the clinical onset and characterization of AD accumulated since then can be used to improve the clinical detection of the disorder, particularly in its earliest symptomatic stages. The construct of MCI has been proposed as a transitional state between the cognitive changes of normal aging and AD. The original definition featured memory deficits in the absence of other cognitive change and was known as "amnestic MCI" (aMCI). However, not all individuals meeting MCI criteria progress to AD. Many factors, such as medications, cognitive defects, and polypharmacy, contribute to MCI in older adults. Criteria for MCI have since been refined to address its heterogeneous etiologies and to identify subtypes without memory deficits or with deficits in multiple cognitive domains. The major interest in MCI, however, remains focused on its relevance as a prodromal state for AD. Dr. Morris contended that the subset of individuals with MCI who will progress to clinically overt AD can already be detected and diagnosed in this stage.

Both the original and the revised criteria for MCI have inherent conceptual difficulties and problems in operationalization that contribute to its heterogeneity. The original criteria for aMCI, which focused on memory deficit, required that the patient self-report memory problems and that they have a clinical dementia rating score of 0.5. Dr. Morris identified problems with these criteria including the subjective nature of the clinical rating of dementia; the unreliability of self-reported memory complaints, which are reported by 44 percent of the healthy, nondemented population; and the fact that people with true memory problems often lack the insight to recognize this and thus do not report it. Defining impairment based upon an individual's performance on a cognitive test compared with the performances of other people is particularly problematic since dementia represents a change for an individual in relation to what he or she once did.

Clinically relevant information as to whether an individual is cognitively impaired is based on the principle of intraindividual change. A person close to the patient may provide the best information in this regard because he or she can describe the patient's cognitive change over time relative to the patient's own cognitive abilities. Such informant-based assessments are powerful tools not only because they allow change to be determined using the patient as his or her own control but because they also evaluate a person's abilities within their own environment and daily activities. One of the biggest disadvantages to implementing an informant-based assessment is the time needed to administer it. Therefore, Dr. Morris used an eight-item, informant-based questionnaire that took three minutes to administer. In a study with 388 individuals, he found that if the informant endorsed two or more of the items in the questionnaire, there was a predictive value of 87 percent for discriminating healthy aging from dementia. The clinical diagnosis of AD in the MCI and pre-MCI individuals was validated by progression to stages of greater dementia severity and by neuropathological AD in 70 of 76 who came to autopsy. Thus, he concluded that pre-MCI diagnosis using informant assessment was more accurate than the aMCI criteria.

Results of a study of 2,660 brains in autopsy suggest that there is a period of at least 10 years of pathology in the brain before sufficient neuronal and synaptic damage occurs to cause the brain to fail, which is subsequently expressed in dementia. Detection of people in the preclinical stage will require biomarkers of disease. Although none have been validated, amyloid imaging using a newly developed compound, Pittsburgh Compound B (PIB-B), as a tracer for amyloid shows promise. The potential sensitivity of PIB-B to identify preclinical AD received further validation in a study with cerebrospinal fluid (CSF) levels of A-b42, another potential biomarker for AD. Patients with PIB-positive scans also had the lowest levels of CSF A-b42, which other studies have shown is lower in demented individuals than controls. Patients with the highest levels of CSF A-b42 had non-Alzheimer's dementia and were PIB negative. This seems to provide further evidence that PIB positivity is a characteristic of patients who have preclinical AD.

Dr. Morris concluded that it is time to revise clinical diagnostic criteria for AD to detect illness in its earliest stages and incorporate new knowledge of the disease. Applying the principle of intraindividual change will broaden diagnostic power to include people for whom AD does not begin with memory impairment. His other suggestions for revising the criteria are:

• Eliminate the age restriction, as it is now known that autosomal dominant AD can begin in the 30s or even 20s.
• Use cognitive tests to support diagnosis rather than as criteria for diagnosis.
• Recognize impairment as intraindividual cognitive decline.
• Discard the MCI construct in favor of etiologic-based diagnoses, most notably early-stage AD.

With these new tools, the notion of MCI can be abandoned for more accurate disease classifications. Finally, the emphasis of AD research will continue to move toward new methods of detecting disease at its earliest stages.

Discussion centered on the clinical application of Dr. Morris's proposed new criteria as well as the ethical implications of an increased ability to predict AD. One Council member asked how prediction information will be used. Dr. Morris cautioned that they have not yet shown conclusively that PIB-positivity in an asymptomatic younger person inevitably leads to dementia; however, he does foresee a time when they can predict with some certainty that an individual will develop AD. Currently, anti-amyloid therapeutics are given to individuals who have received a clinical diagnosis of dementia. However, given that research shows that in demented individuals approximately 50 percent of neurons in certain brain regions are already dead, the drugs may not actually help them. With improvements in disease prediction, these drugs could potentially be given to presymptomatic individuals as an advance treatment target before brain death occurs.

Concern was expressed about laypeople obtaining the informant-based questionnaire through the media and attempting to diagnose their relatives as well as the use of the test outside of the pristine research setting where other variables that affect cognitive function have been eliminated. Dr. Morris clarified that the questionnaire is explicitly a screening test that should be used by physicians to indicate the possible presence of dementia and the need for further evaluation. He also noted that his group has already taken the questionnaire outside of the research setting into a county health system. Despite differences in clientele and physician knowledge, the test remained sensitive. Dr Morris speculated that physicians will still prefer a brain scan to an informant interview, for several reasons: (1) There are obvious differences between a PIB-positive and a PIB-negative scan that do not require interpretation; (2) a scan is a reimbursable test, while the informant interview is not; and (3) effective therapies for AD are lacking. He termed the third reason "therapeutic nihilism," noting that doctors are reluctant to deal with Alzheimer's patients, who usually have a host of behavioral and caregiver issues, because they can offer them little help.

Discussion then turned to the topic of prediction, early diagnosis, and treatment for AD. Dr. Morris confirmed that 25--40 percent of individuals who come to autopsy not having any clinical or positive evidence of cognitive impairment have histopathologic AD. Most of these individuals have a mean age at time of death of about 80 or 85, and the prevalence of AD at 85 is approximately 40 percent. There are three potential explanations for the phenomenon: (1) The plaques, which are being labeled as histopathologic AD, are an epiphenomenon; (2) the individuals indeed have histopathologic AD but have some protective effects against dementia; or (3) the individuals simply did not live long enough to exhibit dementia. He favored the third explanation given his view that AD is a chronic disease similar to atherosclerosis in that the disease pathology begins long before there are clinical symptoms. He estimated that these individuals have histopathologic AD a decade or more before they lose cognitive function. When asked if his assessment means that it is a waste of effort to perform clinical trials of drugs to treat late-stage AD, Dr. Morris responded that if the disease-modifying therapies show an effect on amyloid plaques but do not help the patients, this may be an indictment of when the drugs were given, not the drug itself.

With regard to the studies conducted using CSF, a Council member asked if Dr. Morris looked at other biomarkers. Dr. Morris stated that the biomarker he studied, A-β42, seems to be the most sensitive. There also are biomarkers in serum but the topic is controversial. Although some reports suggest they could be useful, his research shows CSF to be more sensitive. Nevertheless, solid evidence for serum biomarkers would be welcome because obtaining CSF, which requires a lumbar puncture, is much more invasive.

D. Geriatrics and Clinical Gerontology: Studying Aging Versus Aged--The Bogalusa Heart Study

Dr. Gerald Berenson is Research Professor in the Department of Epidemiology and Director of the Tulane Center for Cardiovascular Health at Tulane University. He is also Principal Investigator of the Bogalusa Heart Study.

Dr. Berenson opened his presentation by making several observations about intrinsic aging versus chronologic aging. In western societies, age-related increases in blood pressure, lipids, and body mass index are the norm; however, Dr. Berenson noted, these changes are not seen in primitive societies. Thus, his research goal in the Bogalusa Heart Study was to understand the childhood origin, predictors, and determinants of adult heart diseases and intrinsic aging.

The Bogalusa Heart Study started in 1972 as a National Heart, Lung and Blood Institute (NHLBI) Specialized Center of Research for Arteriosclerosis. This population study is being conducted in a semi-rural, biracial (Black-White) community 70 miles north of New Orleans, LA. After 25 years, the Study was transformed into an NHLBI genetic epidemiologic program. In 2000, the NIA began funding the long-term followup of the Study cohort. The Study design includes approximately 160 substudies.

A primary question driving the Study is whether childhood risk factor variables become risk factors in adults. Three decades of study have shown that, indeed, childhood risk is predictive of adulthood levels. Obesity, total cholesterol, and LDL cholesterol track at a high order, while blood pressure at a lower magnitude is still predictive of adult hypertension. The mixed epidemiological design of repeated cross-sectional and longitudinal studies has shown a dramatic secular trend of increasing obesity (an average of 5 kg [12 lbs] in childhood with no increase in height) and an evolution of adverse levels of risk factors emerging at the young adult ages (19 to 32 years). Other trends show differences by race and gender: relatively high prevalence of obesity in Black females, high rates of hypertension in Blacks, and abnormal levels of high low-density lipoprotein cholesterol and low HDL cholesterol in White males.

The Study also has shown that multiple cardiovascular risk factors, such as blood pressure, adiposity, lipids, and insulin resistance, occur and cluster from childhood into young adulthood at both the high and low levels. This aggregation of risk factors has an additive effect on risk for cardiovascular disease. Studies have shown that obesity beginning in early childhood leads to insulin resistance, and these two factors drive the development of the other risk factors that collectively comprise the metabolic syndrome.

The burden of these risk factors in early life on coronary atherosclerosis is clearly shown by autopsy observations made on Study cohort participants who died from automobile accidents, violence, and suicide. Raised, fibrous plaque lesions in both the aorta and coronary vessels are strongly related to antemortem risk factors. These lesions increase with age and number of risk factors. Cardiovascular imaging studies for subclinical structural/function changes are being conducted more broadly on the study population. Cardiac enlargement and increased left ventricular mass are predicted by obesity and blood pressure from childhood. Carotid intima media thickness (IMT) increased and vascular compliance decreased with increased numbers of risk factors. Parental history of clustered risk factors or cardiovascular disease in parents also relate to increased risk factors in their offspring. Of interest, a lack of parental history of heart disease or low risk factors relates to a low order of risk factors in their offspring and thinner carotid IMT. A family history of longevity is also associated with lower carotid IMT and lower prevalence of metabolic syndrome. Lastly, telomere dynamics, reflective of biological aging and related oxidative stress and inflammation, was studied in pairs of bloods collected 10 years apart from subjects in the Study. These studies indicate greater shortening of telomere length--accelerated aging--in individuals with insulin resistance and excess adiposity.

Observations of the early natural history of cardiovascular disease and risk factors beginning in childhood have helped with development of prevention programs starting in childhood. Particularly successful are the Health Ahead/Heart Smart program for elementary school children and the application of this education program to a Parish (county)-wide model that can be applied to other parts of the Nation.

In response to a question about the role of genetics and the environment in the risk factor "tracking" effect observed from childhood through adulthood, Dr. Berenson responded that he and his colleagues have already begun publishing on candidate genes and genomewide scans.

IX. ADJOURNMENT

The 99th meeting of the National Advisory Council on Aging was adjourned at 1:30 p.m. on September 27, 2006. The next meeting is scheduled for January 30 and 31, 2007.

X. CERTIFICATION

I hereby certify that, to the best of my knowledge, the foregoing minutes and attachments are accurate and complete.3

Richard J. Hodes, M.D.
Chairman, National Advisory Council on Aging
Director, National Institute on Aging

Prepared by Robin Barr, D.Phil.

Attachment A: Roster of the National Advisory Council on Aging

MEMBERSHIP ROSTER
NATIONAL ADVISORY COUNCIL ON AGING
NATIONAL INSTITUTE ON AGING

(Terms end December 31) (*WGoP Member)

Chairperson
Richard J. Hodes, M.D.
Director, National Institute on Aging
National Institutes of Health
Bethesda, MD

*Elizabeth H. Blackburn, Ph.D. (2006)
Professor
Dept of Biochemistry & Biophysics
University of California
San Francisco, CA

Melissa M. Brown, M.D., M.N., M.B.A. (2006)
Director
Center for Value-Based Medicine
Flourtown, PA

Kenneth V. Brummel-Smith, M.D. (2009)
Professor and Chair
Department of Geriatrics
Florida State University College of Medicine
Tallahassee, FL

*John T. Cacioppo, Ph.D. (2007)
Blake Distinguished Service Professor
Department of Psychology
Director, Center for Cognitive and Social Neuroscience
University of Chicago
Chicago, IL

Carl Eisdorfer, Ph.D., M.D. (2009)
Knight Professor and Director
Center on Aging
University of Miami
Miami, FL

*Linda P. Fried, M.D., MPH (2006)
Professor, Medicine, Epidemiology & Health Policy
Director, Division of Geriatric Medicine &
Gerontology
Director, Center on Aging and Health
The Johns Hopkins Medical Institutions
Baltimore, MD

Lawrence M. Friedman, M.D. (2009)
Independent Consultant
11712 Farmland Drive
Rockville, MD

Mary Ganguli, M.D., M.P.H. (2009)
Professor of Psychiatry, Neurology, and Epidemiology
Department of Psychiatry
University of Pittsburgh
Pittsburgh, PA

Alan M. Garber, M.D., Ph.D. (2007)
Director
Center for Primary Care and
Outcomes Research
Center for Health Policy
Stanford University
Stanford, CA

Paul Greengard, Ph.D. (2008)
Vincent Astor Professor
Laboratory of Molecular & Cellular Neuroscience
The Rockefeller University
New York, NY

*Virginia M.-Y. Lee, Ph.D. (2007)
Professor
Dept of Pathology & Laboratory Medicine
Univ of Pennsylvania School of Medicine
Philadelphia, PA

Spero M. Manson, Ph.D. (2006)
Professor of Psychiatry and Head
American Indian & Alaska Native Programs
University of Colorado Health Sciences Ctr
Aurora, CO

Mills, Terry L., Ph.D. (2008)
Associate Dean for Minority Affairs
and Special Programs
Office for Academic Support
and Institutional Services
University of Florida
Gainesville, FL

John C. Morris, M.D. (2009)
Professor
Washington University School of Medicine
St. Louis, MO

Gary B. Ruvkun, Ph.D. (2007)
Professor, Molecular Biology
Massachusetts General Hospital
Boston, MA

Gerald P. Schatten, Ph.D. (2009)
Professor, Pittsburgh Development Center
Magee-Womens Research Institute
University of Pittsburgh
Pittsburgh, PA

Albert L. Siu, M.D., M.S.P.H. (2008)
Ellen and Howard C. Katz Professor
Chairman, Brookdale Department
of Geriatrics and Adult Development
Mount Sinai School of Medicine
The Mount Sinai Medical Center
(and Director, Geriatric Research, Education, and Clinical Center, Bronx Veterans Administration)
New York, NY

*Mary E. Tinetti, M.D. (2008)
Gladys Phillips Crofoot Professor
Department of Internal Medicine, Epidemiology, and Public Health
Director, Program on Aging
Yale University School of Medicine
New Haven, CT

EX OFFICIO MEMBERS

Michael O. Leavitt
Secretary
Department of Health and Human Services
Hubert H. Humphrey Building
Washington, D.C.

Elias Zerhouni, M.D.
Director
National Institutes of Health
Public Health Service
Bethesda, Maryland

James F. Burris, M.D.
Chief Consultant
Geriatrics & Extended Care Strategic
Healthcare Group
Department of Veterans Affairs
Washington, D.C.

Kenneth G. Pugh, M.D.
Commander, MC, U.S. Navy
Department of Medicine
National Naval Medical Center
Bethesda, MD

John Wren
Director, Center for Planning & Policy Development
U.S. Administration on Aging, DHHS
Washington, D.C

1. For the record, it is noted that members absented themselves from the meeting when the Council discussed applications (a) from their respective institutions or (b) in which a conflict of interest may have occurred. This procedure only applied to applications that were discussed individually, not to "en bloc" actions. (Back to text.)
   
   
2. For the record, it is noted that members absented themselves from the meeting when the Council discussed applications (a) from their respective institutions or (b) in which a conflict of interest may have occurred. This procedure only applied to applications that were discussed individually, not to "en bloc" actions. (Back to text.)
   
   
3. These minutes will be approved formally by the Council at the next meeting on January 30-31, 2007, and corrections or notations will be stated in the minutes of that meeting. (Back to text.)