A current primary focus in the prevention and treatment of dementia is the identification of the disease at its earliest possible stages. The proposed study will determine the prevalence, incidence, and progression of mild cognitive impairment (MCI), a condition thought to reflect incipient dementia, in a community-based cohort of older adults and will examine its relationship to specific cardiovascular risk factors. Prevalence and- incidence rates of MCI and its subtypes will be identified through careful cognitive screening and diagnostic evaluation of participants in the Alzheimer's Disease Patient Registry/Adult Changes in Thought cohort, identified from a large stable HMO population with extensive computerized medical and pharmacological records. Subsequent annual follow-up assessments during the incidence phase will permit thorough analysis of cognitive change over time associated with each MCI subtype, and will help determine whether the use of an individualized estimate of premorbid status as a benchmark better predicts MCI progression. We will also determine whether cardiovascular risk factors shown to increase the risk of AD are associatedwith the diagnosis and progression of MCI, or conversely, reversion to normal cognitive function. Two such risk factors, elevated fasting plasma insulin and 24S-hydroxycholesterol levels, will be measured initially in all prevalent cases and annually in incident cases and controls.
A final aim of this study is to establish a platform for exploratory analyses of interactions with other risk factors such as APOE genotype, gender, and BMI, for future determination of the effects of treating insulin resistance and impaired cholesterol metabolism on MCI incidence, progression, and reversion to normal cognitive function in this sample. In addition, blood will be collected and banked to explore other promising biomarkers as they are identified. The results of this study will provide valuable information concerning the incidence and natural history of MCI, and its relation to various risk factors that may be amenable to therapeutic intervention.
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