This proposal seeks renewal of a prospective, observational cohort study of the natural history of, and risk factors for, the onset of physical disability in older women, in order to complete the observation of the evolution of function in the cohort in 3 additional examinations 18 months apart. This would permit completion of the initial specific aims and addressing additional related questions that have developed from our findings. Meeting these objectives will provide new bases for screening for those at high risk of disability and for early interventions to prevent the onset of disability. The goals of this renewal are to: 1) complete determination of the characteristics and natural history of preclinical disability in two major, distinct and parallel casual pathways to physical disability: one caused by diseases that affect mobility and exercise tolerance, and the second caused by decrements in cognition. We will determine the measures of preclinical disability that predict progression to disability in each pathway and are, thus, markers of high risk; 2) define who does, or does not, implement modifications that characterize preclinical disability. This could provide insight into adaptations that slow the decline in function in those who do not employ them; 3) determine the predictors and modifiers of decline in function over time, and of remaining high functioning; and 4) develop practical clinical nomograms for screening for those at risk of disability in each pathway, and overall. The study participants are a population-based sample of 436 community-dwelling women who were 70 to 79 years of age and high functioning in 1994-5 at the time of recruitment. They completed one follow-up examination since then, and a second follow-up examination is currently being completed, each 18 months apart. Examinations are performed in the Functional Status Laboratory within the Outpatient General Clinical Research Center, and include ascertainment of both functional outcomes and chronic diseases and other hypothesized risk factors, as well as measurement of change over time. As this cohort has, to date, primarily developed early changes in mobility function, we propose 3 additional examinations, 18 months apart, to observe the progression of mobility preclinical and clinical mobility disability to the development of difficulty in tasks essential to independent living. We also have evidence of early changes in cognitive function in the cohort and indications of potential preclinical indicators of resulting functional decline; further follow-up would determine the prognostic import of these finding and gain insight into opportunities for amelioration of such functional losses. It would also confirm our hypothesis that there are 2 parallel pathways to disablement: via cognitive decline and via mobility and exercise tolerance losses. Completing the follow-up of this cohort in the next funding period will permit understanding the preclinical phase of disablement due to chronic, progressive disease and cognitive impairment, the process and risk factors for progression to task disability and dependency. In selected instances, data from the complementary Women's Health and Aging Study I, a study of the 1/3 most disabled older women in the community, will be combined with this cohort to enhance the power and precision of our analyses. The resulting insights should provide new opportunities for screening and prevention of physcial disability in older women- the population subgroup at highest risk for disability at older ages.
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