Individuals who have a family history (FH) of Alzheimer disease (AD) or who carry the apolipoprotein E ⑀4 allele are at increased risk for developing AD. Abnormalities in brain event-related potentials (ERPs) have been observed in patients diagnosed as having AD. Objective: To determine whether groups of nonsymptomatic, middle-aged individuals at increased risk for AD exhibited ERP changes consistent with this disease. Design: In a case-control study, ERPs were elicited using an auditory

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... paradigm, and a brief neuropsychological battery was administered. Setting: University laboratory facilities. Subjects: We compared age-matched and educationmatched groups with a positive family history (FH+; n = 24) or a negative family history (FH−; n = 23) of AD. Within the FH+ group, subgroups were identified as either carriers of the apolipoprotein E ⑀4 allele (⑀4+; n = 9) or noncarriers (⑀4−; n = 8), and these subgroups were compared with the FH− group. Main Outcome Measures: The latency and amplitudes of P3, N2, and P2 components of the ERP were quantified and analyzed statistically. Results: Compared with the FH− group, both the whole FH+ group and the FH+/⑀4+ subgroup showed abnormal prolongation in the latency of the P3 component. In addition, the FH+/⑀4+ subgroup showed abnormal prolongation in the latency of the N2 component. These changes were observed in the absence of neuropsychological deficits. Conclusions: The findings indicate that groups at increased risk for developing AD show ERP changes consistent with those observed in patients diagnosed as having AD. The results support accumulating evidence that AD has a preclinical phase and that early detection may be possible.