The overall aim of this application is to identify magnetic resonance imaging (MRI) and 1H magnetic resonance spectroscopic (1HMRS) measurements which will aid in prospectively identifying individuals who subsequently develop Alzheimer's Disease (AD). We will study three clearly distinguishable clinical groups: 1) cognitively normal elderly controls, 2) patients with probably AD, and 3) risk for developing AD. Patients and controls will be drawn from the Mayo Alzheimer's Disease Registry (AG06786) and Alzheimer's Disease Center (AG0803).
Aim #1 : We will develop age and gender specific normative values for the MRI/MRS measurements.
Aim #2 : A multivariate model will be developed with the distinction between AD and controls as the dependent variable. Independent variable swill be hippocampal volume, temporal horn volume, brain volume, ventricular volume, 1HMRS metabolic ratios (NAA/Cr, mI/Cr, NAA/mI), leukoariosis volume, the annual percent change in each of the preceding MR variables, age, family history, education, and apolipoprotein E genotype.
Aim #2 will entail testing the hypothesis that each of the preceding variables is significantly associated with the diagnosis of AD.
Aim #3 : Univariate analyses will be performed testing the hypothesis that a significant association exists between crossover of MCI patients to AD and each of the independent variables which were demonstrated to be significant in Specific Aim #2. Crossover is defined as the conversion of a patient from the diagnostic category of MCI to the diagnosis of AD.
Aim #4 : Using only those MRI/MRS, clinical, and laboratory predictor variables which were significant in Aim #3, we will develop a multivariate mathematical model for predicting crossover of MCI patients to AD. This will allow us to test the hypothesis that each MRI/MRS variables has power to predict crossover which is independent of an additive to other predictor variables.
Aim #5 : Decline in cognition will be modeled as a function of the MRI/MRS, clinical, and laboratory variables listed in Aim #2 for the controls and MCI patients. We will test the hypothesis that specific MR measures are associated with decline in specific measures of cognition.
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