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Neural Processing of Novel Events Disrupted in Early Alzheimer's Disease

Patients in the mild to moderate stages of Alzheimer's disease (AD) often seem apathetic and fail to attend to novel stimuli. In EEG studies of normal subjects, the P3 event-related potential has been shown to be an index of neural processes involved in attending to novel events. These investigators sought to determine whether disruption of the novelty P3 response could help explain important behavioral changes seen in AD.

Ten subjects with probable early AD and 20 controls matched for age, sex, and education viewed a repetitive background, an infrequent target stimulus (a geometric figure), and infrequent novel stimuli (fragmented or "impossible" figures). P3 response to target stimuli did not differ between the groups; however, the amplitude of P3 response to novel stimuli was smaller in subjects with AD than in controls. Subjects with AD did not inspect the novel stimuli for as long as controls did, and inspection times correlated with the amplitude of the P3 potentials.

Comment: This well-designed study has important theoretic and pragmatic implications: From a theoretic perspective, it suggests that in early AD patients develop a deficit in the system that mediates the orienting response to novel stimuli. Other investigators (see, for example, Rev Neurosci 1998; 9:57) have demonstrated that the ability to orient to unexpected events is mediated by a network involving frontal, temporal-parietal, and limbic structures. The P3 response to target and "oddball" stimuli is mediated by a similar network, and research is needed to identify the part of this network that is critical for novel, but not target, stimuli. Still other investigators have shown that anticholinergic medications such as scopolamine may interfere with the production of P3. Although the cholinergic system is affected in AD, the role of this neurotransmitter in producing changes in P3 remains to be determined.

In the immediate future, treatments that fully restore cognitive functions are not likely to be available to patients with moderate to severe AD. Thus, prevention and early intervention may be critical in maintaining quality of life. Several agents, including antioxidants and cholinergic agents, appear promising and are undergoing extensive study. That the disruption was apparent even in the patients with normal Mini-Mental Status Examination scores in this study suggests that the P3 novelty response may be the instrument that will allow us to determine who needs early therapy.

— KM Heilman

Kenneth M. Heilman, MD, is James E. Rooks, Jr., Distinguished Professor of Neurology and Program Director, University of Florida College of Medicine, Gainesville, FL.

Published in Journal Watch Neurology August 23, 2001

Citation(s):

Daffner KR et al. Pathophysiology underlying diminished attention to novel events in patients with early AD. Neurology 2001 May 22 56 1377-1383.

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