The specific aims of the Clinical Core are threefold: (1). To prospectively follow five longitudinal cohorts of subjects at risk for neurodegenerative dementia. The central hypothesis of the UTSW ADC is that vascular risk factors in elderly individuals are important contributors to neurodegenerative dementias, and that such patients can be identified by their clinical and psychometric profile, neuroimaging studies, and biochemical markers. Support for this hypothesis will be obtained through prospectively following 5 cohorts: (a). Patients with Mild Cognitive Impairment (MCI). A cohort of 150 subjects with MCI (CDR = 0.5) will be recruited and followed for three years or until they convert to AD. (b). Patients with early Alzheimer's disease (AD). 150 subjects with possible or probable AD in the early stages of their illness (CDR = 1) will be followed for until they progress to CRD = 2. (c). Patients with non-AD dementias. A cohort of 100 patients with non-AD dementia (50 with Fronto-temporal dementia (FTD), and another 50 with dementia and psychotic features (presumed Lewy-body disease (LBD)) will be recruited and followed until death, (d). Controls for cohorts (a) - (c): 150 subjects with no cognitive complaints will be recruited from among spouses, caregivers, and siblings of subjects enrolled in cohorts (a) - (d). (e). Native American cohort. Subjects with dementia (50 subjects) and matched controls recruited at our Satellite clinic in Talahina, OK will be followed prospectively until death. All cohorts will receive uniform evaluations, including MRI scans and biomarker assays for candidate plasma markers and genetic polymorphisms. Substantial efforts will be made to obtain a high autopsy rate among subjects enrolled in the longitudinal cohorts. (2). To support investigator-initiated research on neurodegenerative dementias by researchers at UT Southwestern. A key function of this Core is to provide logistical support and a source of well-studied patients and biological fluids for investigator-initiated projects (funded through RO1, RO3, K23, NACC, Alzheimer's Association, or philanthropic organizations) by UTSW faculty. Several of these are ongoing and discussed in the narrative. All patients enrolled in these studies receive a uniform evaluation, as the Clinical Core Cohorts (in specific aim (1) above). (3). To support multi-institutional observational studies and clinical trials in neurodegenerative dementias. Since much important research on neurodegenerative disorders requires large cohorts that can only be obtained through large collaborative efforts, the third aim of the Clinical Core is to support the participation by the UTSW ADC in multi-center studies. At present these include the NIA Genetics Initiative, FTD-PET study, and multiple clinical trials sponsored by the AD Cooperative Study. All patients enrolled in these studies receive a uniform evaluation, as the Clinical Core Cohorts (in specific aim (1) above).
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