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 associated with 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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG024180-02
Application #
7211470
Study Section
Special Emphasis Panel (ZRG1-HOP-C (90))
Program Officer
Anderson, Dallas
Project Start
2006-04-01
Project End
2011-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
2
Fiscal Year
2007
Total Cost
$496,594
Indirect Cost
Name
Seattle Institute for Biomedical/Clinical Research
Department
Type
DUNS #
928470061
City
Seattle
State
WA
Country
United States
Zip Code
98108
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Cholerton, Brenna; Baker, Laura D; Trittschuh, Emily H et al. (2012) Insulin and sex interactions in older adults with mild cognitive impairment. J Alzheimers Dis 31:401-10
Trittschuh, Emily H; Crane, Paul K; Larson, Eric B et al. (2011) Effects of varying diagnostic criteria on prevalence of mild cognitive impairment in a community based sample. J Alzheimers Dis 25:163-73
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