Established in 1994, the Cache County Study is a population-based longitudinal investigation of dementia in relation to genetic and environmental antecedents. The renewal of this important work will capitalize on nine years of prospective observation in this epidemiological cohort and will have available longitudinal cognitive assessments in the entire sample. Using these observations, we will empirically define the early cognitive trajectory of preclinical Alzheimer's disease (AD) and the relationship of antecedent exposures to the rate of decline and to categorical outcomes of dementia. There are four major specific aims of the project, which are as follows: 1. Conduct two more triennial waves of screening (Waves 3 and 4) among Cache County residents not demented at prior screenings. Use the nine years of observation to examine the trajectory of cognitive change to dementia and to obtain more precise estimates of the incidence of AD, especially after age 85. 2. Use an expanded cognitive screening battery for proposed Waves 3 and 4. Examine the efficiency of the new battery as a screen for dementia. Also, use the resulting expanded information base to extend existing data on trajectory of cognitive functioning to a nine-year time interval. With this new information, examine: a) Individual (cross sectional) features of cognitive dysfunction, or clusters of such features, that most strongly predict subsequent development of dementia; b) Nature and extent of change in such features or their clusters over time, including specifically a search for changes that most strongly predict the development of dementia; c) Various operationally defined categories of cognitive impairment (e.g., """"""""Mild Cognitive Impairment"""""""" [MCI], etc.) and compare their abilities to predict subsequent dementia. 3. Extend prior studies of the influence of genetic and environmental factors on risk of AD, noting whether these same factors predict tragectory of cognitive decline as a prodrome of AD. 4. Continue and extend the study's existing autopsy program, expanding its aims to clinically diagnosed dementia subtypes and to unaffected participants, particularly those with risk factors for dementia (age 85+, MCI).
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