The purpose of this study is to identify the individuals with the highest risk to develop AD. To accomplish this goal we will conduct a longitudinal study on at-risk individuals who have been identified based on the presence of mild cognitive impairment (MCI). The subjects were part of the Pittsburgh cohort of the Dementia Study of the Cardiovascular Health Study (CHS). The CHS Dementia study ended in 1999, and the present study will follow those participants identified as MCI or normal control. Specifically, we study 142 MCI subjects and 218 controls with detailed neurobehavioral, neuroimaging, and neurological examinations. Each of these former CHS participants had clinical and neuropsychological exams, MRI studies, and blood samples in 1992-93 and 1997-98. In 1998-1999, each of these participants had detailed neuropsychological, psychiatric, and neurological testing that allowed us to identify a clear and well- characterized cohort of MCI and normal elderly individuals. Consequently, we are in the unique position to examine the natural history of the development of AD in a population-based sample. The study will make use of prospective structural and perfusion MRI- scans, genetic factors (e.g., apolipoprotein E epsilon4 allele), biological markers (e.g., inflamation markers [Inter-leukin-6, C- reactive protein, and Tumor necrosis factor alpha) and plasma beta amyloid level [Abeta1-40 and Abeta 1-40]), and specific neuropsychological measures as markers for the development of AD. We propose that there are two types of MCI: 1) The MCI amnestic- type, which represents a distinct entity, with a significantly increased risk to develop AD (10 percent per year). 2) the MCI multiple cognitive deficit-type, which represents a temporal elongation of the normal transition from aged to AD. Consequently, these participants will have a reduced risk to develop AD (5 percent per year).
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