This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This is a non-randomized natural history non-treatment study in which a total of 800 subjects including 200 normal controls, 400 individuals with MCI, and 200 subjects with mild AD will be recruited at approximately 50 sites in the United States and Canada for longitudinal follow up. Each site's goal will be to recruit 8 subjects with Mild Cognitive Impairment, 4 subjects with Alzheimer's disease and 4 Healthy Elderly Controls.The major goals of the ADNI are to: 1. Develop improved methods which will lead to uniformstandards for acquiring longitudinal, multi-site MRI and PET data on patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), and elderly controls. 2. Acquire a generally accessible data repository which describes longitudinal changes in brain structure and metabolism. In parallel, acquire clinical cognitive and biomarker data for validation of imaging surrogates.3. Develop methods which will provide maximum power to determine treatment effects in trials involving these patients.4. Test a series of hypotheses based on the clinical and biomarker data as outlined in the statistical analysis section. Hypothesis:A.2. HYPOTHESIS TESTINGThe major goal of this initiative is the collection of data rather than its analysis. In addition to carrying out the clinical initiative, we will test several hypotheses based on the clinical and biomarker data. A few examples are listed below:1. Rates of conversion from MCI to AD will average 10-15%/year.2. Baseline scores on logical memory and apolipoprotein E (APOE) epsilon 4 (APOE4) status will predict conversion from MCI to AD.3. Measures of global functioning such as activities of everyday living will be more sensitive than neuropsychological measures for predicting conversion from MCI to AD.4. The rate of backcrossing from MCI to normal will be extremely low for thispopulation.5. Plasma isoprostanes will a) be related to disease severity and b) higher levels will predict a faster rate of decline.6. Hippocampal volume and posterior cingulate glucose metabolic rate will predict rate of decline and conversion from MCI to AD.
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