The goal of the proposed research is the development of a non-invasive electrophysiological test that can be used as a sensitive marker of memory dysfunction during the very early stage of probable Alzheimer's disease (AD). Such markers may provide a rapid and reliable screen for assessing pharmacological interventions. The P300 component of long latency evoked potentials have been extensively used to study age and disease induced alterations in cognitive function. Recent reports from a number of laboratories, including ours, have indicated that the utility if it is recorded in the context of tasks that impose some demand or """"""""stress"""""""" on memory. The feature of the P300 that appears to be predictive of memory dysfunction is a substantial attenuation of its amplitude. In a preliminary experiment, we recorded the P300 during a modified Sternberg memory scanning task with letters as probes. When a memory load of one item was used for eliciting the P300, patients diagnosed with presumed early AD sis not significantly differ from age-matched controls either in the latency or amplitude of the P300. With increasing memory loads, however, the P300 practically disappeared in AD patients and age- matched controls when memory loads of 2-5 items were used. In contrast, there was no differential effect of memory load on the latency of P300 in AD patients compared to age-matched controls. The purpose of the present proposal is to extend and refine our observations in a much larger population of AD patients during the early stages of the disease and age-matched controls. In addition, a group of patients with """"""""age-associated memory impairment"""""""" will be studied and followed up to determine whether electrophysiological tests can distinguish those at risk for AD. Both verbal and spatial tasks will be used to elicit the P300 and potentials will be recorded for midline as well as lateralized sites to assess the differential vulnerability of each during normal aging and in AD patients.
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