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

From the Brigham Behavioral Neurology Group and Laboratory of Higher Cortical Functions (Drs. Daffner, Rentz, Scinto, Budson, and R. Faust), Division of Cognitive and Behavioral Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston; and the Department of Psychology (Dr. Holcomb), Tufts University, Medford, MA.

Address correspondence and reprint requests to Dr. Kirk R. Daffner, Division of Cognitive and Behavioral Neurology, Brigham and Women’s Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115; e-mail: kdaffner{at}parners.org

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 event-related potentials were recorded, mildly impaired AD patients and matched normal controls (NC) viewed line drawings that included a repetitive background stimulus, an infrequent target stimulus, and infrequent novel stimuli. Subjects controlled how long they viewed each stimulus by pressing a button. This served as a measure of their allocation of attention. They also responded 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 significantly smaller for AD patients than NC. However, P3 amplitude to target stimuli did not differ between groups. For NC, P3 response to novel stimuli was much larger than to background stimuli. In contrast, for patients with AD, there was no difference in P3 response to novel vs background stimuli. Although NC spent more time looking at novel than background stimuli, patients with 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 (R² = 0.52) and inversely correlated with apathy severity.

CONCLUSIONS: The decreased attention to novel events exhibited by patients with AD cannot be explained by a nonspecific reduction 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.

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