Pathophysiology underlying diminished attention to novel events in patients with early AD

Background: Patients with mild to moderate AD often are apathetic and fail to attend to novel aspects of their environment. Objective: To investigate the mechanisms underlying these changes by studying the novelty P3 response that measures shifts of attention toward novel events. Methods: While even t-related potentials were recorded, mildly impaired AD patients and matched normal controls (NC) viewed line drawings that included a repetitive backg round stimulus, an infrequent target stimulus, and infrequent novel stimuli . Subjects controlled how long they viewed each stimulus by pressing a butt on. This served as a measure of their allocation of attention. They also re sponded to targets by depressing a foot pedal. Patients did not differ from NC in age, education, estimated IQ, or mood but were judged by informants to be more apathetic. Results: P3 amplitude to novel stimuli was significan tly smaller for AD patients than NC. However, P3 amplitude to target stimul i did not differ between groups. For NC, P3 response to novel stimuli was m uch larger than to background stimuli. In contrast, for patients with AD, t here was no difference in P3 response to novel vs background stimuli. Altho ugh NC spent more time looking at novel than background stimuli, patients w ith AD distributed their viewing time evenly. Remarkably, for patients with AD, the amplitude of the novelty P3 response powerfully predicted how long they would spend looking at novel stimuli (R-2 = 0.52) and inversely corre lated with apathy severity. Conclusions: The decreased attention to novel e vents exhibited by patients with AD cannot be explained by a nonspecific re duction in their attentional abilities. The novelty P3 response is markedly diminished in mild AD, at a time when the target P3 response is preserved. The disruption of the novelty P3 response predicts diminished attention to novel stimuli and is associated with the apathy exhibited by patients with AD.