There are two aims of this renewal proposal: first, to develop computer-analyzed electroencephalography (CEEG) more fully as a tool for the differential diagnosis of dementia; and second, to begin to establish links between brain functional abnormalities seen on CEEG and structural lesions seen on magnetic resonance imaging (MRI) scans. There are six steps in this research plan. First, new subjects will be recruited for the existing cohort of subjects with Alzheimer's disease (DAT), multi-infarct dementia (MID), and normal control subjects (CON). Second, subjects will recruited for three additional groups: those with major depressive episode, dementia of affective disorder (DAD), and dementia of other etiologies. All subjects being evaluated for dementia will undergo a thorough evaluation which will include mental statu testing, neuropsychological testing, neurologic examination, a battery of relevant laboratory tests, as well as MRI scanning. Third, all subjects will undergo conventional EEG studies, which will be interpreted by an electroencephalographer, as well as CEEG studies. Fourth, all MRI scans will be quantitatively rated by two neuroradiologists for the severity and location of deep white-matter lesions, periventricular lucencies, and atrophy. MRI scans will be correlated with CEEG topographic maps to detect co-localization of functional and structural lesions. Fifth, subjects will be reassessed on an annual basis (or more frequently if suggested by their clinical situation) with an interview of subjects and family, mental status examination, EEG and CEEG procedures, and any other tests which are clinically indicated. Sixth, we will follow subjects to autopsy to confirm clinical diagnoses and to correlate MRI lesions with neuropathological findings. Specific experimental hypotheses regarding the sensitivity and specificity of CEEG measures, the significance of lesions seen on MRI, and the capacity to co- localize functional and structural lesions will be tested.

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National Institute of Mental Health (NIMH)
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Life Course and Prevention Research Review Committee (LCR)
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University of California Los Angeles
Schools of Medicine
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Morgan, Melinda L; Cook, Ian A; Rapkin, Andrea J et al. (2007) Neurophysiologic changes during estrogen augmentation in perimenopausal depression. Maturitas 56:54-60
Hunter, Aimee M; Leuchter, Andrew F; Morgan, Melinda L et al. (2006) Changes in brain function (quantitative EEG cordance) during placebo lead-in and treatment outcomes in clinical trials for major depression. Am J Psychiatry 163:1426-32
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Morgan, Melinda L; Cook, Ian A; Rapkin, Andrea J et al. (2005) Estrogen augmentation of antidepressants in perimenopausal depression: a pilot study. J Clin Psychiatry 66:774-80
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Cook, Ian A; Leuchter, Andrew F; Morgan, Melinda L et al. (2004) Longitudinal progression of subclinical structural brain disease in normal aging. Am J Geriatr Psychiatry 12:190-200
Krell, Heather V; Leuchter, Andrew F; Morgan, Melinda et al. (2004) Subject expectations of treatment effectiveness and outcome of treatment with an experimental antidepressant. J Clin Psychiatry 65:1174-9
Leuchter, Andrew F; Morgan, Melinda; Cook, Ian A et al. (2004) Pretreatment neurophysiological and clinical characteristics of placebo responders in treatment trials for major depression. Psychopharmacology (Berl) 177:15-22

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