application): This is the first application for a Mentored Clinical Scientist Development Award from the University of California at San Francisco on behalf of Kristine Yaffe, M.D. The applicant s goal is to develop the multidisciplinary skills necessary to become a leading independent investigator in dementia research. Developmental plans include a program of course work, research seminars, and structured mentoring, as well as a research project directed toward prevention and treatment of cognitive decline and dementia in the elderly. Specifically, the applicant will investigate the role of estrogen-like drugs for prevention of preclinical cognitive decline and dementia. She has chosen studies of different methodologies (randomized trial, cross-sectional, and prospective) in order to answer several complementary questions and to further her understanding of the strengths and limitations of various study designs. This proposal has three specific aims: (1) To determine whether elderly women using postmenopausal estrogen have better baseline cognitive function and less cognitive decline over a six year period than women not taking estrogen, (2) To determine whether elderly women treated for four years with a new selective estrogen receptor modulator, raloxifene, have better cognitive function and less incidence of dementia than women treated with placebo, (3) To determine if biologic markers of estrogen status, such as bone mineral density, serum estradiol levels, and different estrogen receptor genotypes, are associated with cognitive function in elderly women.
The specific aims will be achieved by analyzing data from the ongoing Study of Osteoporotic Fractures (SOF), a prospective study of nearly 10,000 elderly community-dwelling women, and from the Multicenter Osteoporosis Raloxifene Evaluation (MORE) trial of over 7,000 women who were randomized to raloxifene or placebo. Both studies include large numbers of elderly women who were not demented at baseline and who receive periodic cognitive testing during the studies. If this promising preventive intervention proves effective, millions of women could preserve their cognitive capacity and maintain their independence and quality of life. This award will foster the applicant's development towards becoming an independent investigator in aging research.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AG000888-02
Application #
6055347
Study Section
National Institute on Aging Initial Review Group (NIA)
Project Start
1998-09-30
Project End
2003-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Sink, Kaycee M; Covinsky, Kenneth E; Barnes, Deborah E et al. (2006) Caregiver characteristics are associated with neuropsychiatric symptoms of dementia. J Am Geriatr Soc 54:796-803
Barnes, Deborah E; Tager, Ira B; Satariano, William A et al. (2004) The relationship between literacy and cognition in well-educated elders. J Gerontol A Biol Sci Med Sci 59:390-5
Sink, Kaycee M; Covinsky, Kenneth E; Newcomer, Robert et al. (2004) Ethnic differences in the prevalence and pattern of dementia-related behaviors. J Am Geriatr Soc 52:1277-83
Yaffe, K; Lindquist, K; Penninx, B W et al. (2003) Inflammatory markers and cognition in well-functioning African-American and white elders. Neurology 61:76-80
Lui, Li-Yung; Stone, Katie; Cauley, Jane A et al. (2003) Bone loss predicts subsequent cognitive decline in older women: the study of osteoporotic fractures. J Am Geriatr Soc 51:38-43
Barton, Cynthia; Miller, Bruce; Yaffe, Kristine (2003) Evaluation of the diagnosis and management of cognitive impairment in long-term care. Alzheimer Dis Assoc Disord 17:72-6
Yaffe, Kristine; Edwards, Emily R; Lui, Li-Yung et al. (2003) Androgen receptor CAG repeat polymorphism is associated with cognitive function in older men. Biol Psychiatry 54:943-6
Trinh, Nhi-Ha; Hoblyn, Jennifer; Mohanty, Subhanjoy et al. (2003) Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta-analysis. JAMA 289:210-6
Mehta, Kala M; Yaffe, Kristine; Langa, Kenneth M et al. (2003) Additive effects of cognitive function and depressive symptoms on mortality in elderly community-living adults. J Gerontol A Biol Sci Med Sci 58:M461-7
Mehta, Kala M; Simonsick, Eleanor M; Penninx, Brenda W J H et al. (2003) Prevalence and correlates of anxiety symptoms in well-functioning older adults: findings from the health aging and body composition study. J Am Geriatr Soc 51:499-504

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