Converging lines of evidence suggest that age-related changes in cognition, and particularly, executive function may exert downstream effects on physical function. However, there is a paucity of data regarding the role of these functions in the natural history of physical disability. We propose to address this gap by building on an established ongoing prospective cohort study of initially high-functioning women, aged 70-80 at baseline, the Women's Health and Aging Study II (WHAS II). Thus, our first aim of this ancillary study is to characterize rates of change in various domains of cognitive function over a 9-year interval. Less clear is whether these changes in cognition predict performance-based changes and self-reported transitions to preclinical difficulty independent of the well-studied mobility pathway. Thus, our second aim will be to test the value of a cognitive pathway to preclinical difficulty and disability in three groups of functional outcomes, categorized according to the putative demands they place on mobility, cognition, or both pathways. Our third set of aims will parallel the WHAS II's innovative efforts to assess preclinical functional difficulty in the mobility pathway by developing more valid and sensitive assessment method to better capture functional changes and compensations in complex activities of daily living typically not reported using standard self-report methods.
Our fourth aim seeks to translate these epidemiologic findings into clinical terms by exploring how threshold relationships between cognition and physical function correspond to standard clinical indices of cognitive impairment. The WHAS II offers a unique opportunity to explore in-depth causal pathways between cognition and progression to physical disability for numerous reasons. The majority of women have been retained and evaluated over repeated intervals using state-of-the-art self-report measures comprehensive assessments of mobility, basic, and complex physical functions, and, a uniquely enriched cognitive protocol, developed extensively by the principal investigator. We will synthesize research findings from this study toinform the broader aims of the WHAS II renewal study to develop a conceptual framework that prospectively identifies precursors and major pathways in the natural history of disability. Understanding the roles that cognition may play in the transitions to disability will provide opportunities for better identifying at-risk individuals and developing targeted primary and secondary preventive interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
3R01AG019825-04S1
Application #
7174047
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Elias, Jeffrey W
Project Start
2002-09-30
Project End
2007-08-31
Budget Start
2006-02-15
Budget End
2006-08-31
Support Year
4
Fiscal Year
2006
Total Cost
$57,611
Indirect Cost
Name
Johns Hopkins University
Department
Other Health Professions
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Mielke, Michelle M; Bandaru, Veera Vankata Ratnam; Haughey, Norman J et al. (2012) Serum ceramides increase the risk of Alzheimer disease: the Women's Health and Aging Study II. Neurology 79:633-41
Carlson, Michelle C; Parisi, Jeanine M; Xia, Jin et al. (2012) Lifestyle activities and memory: variety may be the spice of life. The women's health and aging study II. J Int Neuropsychol Soc 18:286-94
Mielke, Michelle M; Haughey, Norman J (2012) Could plasma sphingolipids be diagnostic or prognostic biomarkers for Alzheimer's disease? Clin Lipidol 7:525-536
Yasar, Sevil; Ko, Jean Y; Nothelle, Stephanie et al. (2011) Evaluation of the effect of systolic blood pressure and pulse pressure on cognitive function: the Women's Health and Aging Study II. PLoS One 6:e27976
Mielke, Michelle M; Bandaru, Veera Venkata Ratnam; Haughey, Norman J et al. (2010) Serum sphingomyelins and ceramides are early predictors of memory impairment. Neurobiol Aging 31:17-24
Rosenberg, Paul B; Mielke, Michelle M; Xue, Qian-Li et al. (2010) Depressive symptoms predict incident cognitive impairment in cognitive healthy older women. Am J Geriatr Psychiatry 18:204-11
Carlson, Michelle C; Xue, Qian-Li; Zhou, Jing et al. (2009) Executive decline and dysfunction precedes declines in memory: the Women's Health and Aging Study II. J Gerontol A Biol Sci Med Sci 64:110-7

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