The research goal is to determine if event-related potentials (ERPs) elicited during semantic processing of to-be-remembered words can differentiate subjects with age-associated memory impairment (AAMI) from those in the pre-dementia stages of Alzheimer's Disease (AD). The diagnosis of AD is very difficult in the earliest stages, when individuals commonly experience impairment of recent memory which may be indistinguishable from that observed in AAMI.
The specific aims of the proposed study are to: 1) Replicate the investigators preliminary findings of diminished N200-P300 amplitude and prolonged P300 latency in mild AD, using a larger, carefully selected and neuropsycholigically defined group of experimental and control subjects. 2) Extend these ERP findings by following a group of subjects with AAMI longitudinally, to determine if these ERP parameters can predict which subjects are at risk of developing dementia. Phase I (years 1 and 2) will measure the above ERP parameters in 40 experimental subject meeting NINCDS-ADRDA work group criteria for AD, probable and having a mild level of dementia (Global Deterioration Scale 4). They will receive comprehensive physical and psychological examinations, and ERP recordings will be made during the classic auditory be-boop paradigm as well as four semantic word-sorting tasks. 40 control subjects matched for age, sex, and educational level will undergo identical examinations and ERP procedures. The mean N200-P300 amplitude and P300 latency will be compared between groups for each of the ERP paradigms to test for significant differences. Phase II (years 1 to 5) will follow a cohort of 100 subjects wish AAMI longitudinally. During years 1 and 2, the cohort will be enrolled following comprehensive physical and psychological examinations and determination that they manifest signs and symptoms consistent with Global Deterioration Scale 3. They will all receive baseline ERP procedures identical to those of the Phase I subjects. Physical and psychological examinations and ERP procedures will ba repeated once for all Phase II subjects during year 3 or 4, and once again for all possible Phase II subjects during year 5. It is anticipated that approximately 10% of the cohort will drop at least one standard deviation on tests of memory nd one or more other cognitive functions. A determination will ba made of whether their ERP parameters predated and predicted the drop.
