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Different brain networks mediate task performance in normal aging and AD

Defining compensation

From the Departments of Neurology (Drs. Stern, Marder, and Bell), Psychiatry (Drs. Stern, Moeller, Anderson, Luber, Marder, and Sackeim and C.E. Campbell), and Radiology (Dr. Van Heertum) and the Cognitive Neuroscience Division of the Sergievsky Center (Drs. Stern and Anderson and N.R. Zubin, A.A. DiMauro, and A. Park), College of Physicians and Surgeons of Columbia University; The Alzheimer’s Disease Research Center in the City of New York (Drs. Stern, Anderson, Marder, and Bell); and the Department of Biological Psychiatry (Drs. Stern, Moeller, Luber, and Sackeim), New York State Psychiatric Institute, New York, NY.

Address correspondence and reprint requests to Dr. Stern, Sergievsky Center, 630 W 168th Street, New York, NY 10032; e-mail: ys11{at}columbia.edu

OBJECTIVE: To determine whether the pathologic mechanisms of AD alter the brain networks subserving performance of a verbal recognition task.

BACKGROUND: Functional imaging studies comparing task-related activation in AD patients and controls generally have not used network analysis and have not controlled for task difficulty.

METHODS: H₂¹⁵O PET was used to measure regional cerebral blood flow in 14 patients and 11 healthy elders during the performance of a serial verbal recognition task under two conditions: low demand, with study list size (SLS) equal to one; and titrated demand, with SLS adjusted so that each subject recognized words at 75% accuracy. The Scaled Subprofile Model was used to identify networks of regionally covarying activity across these task conditions.

RESULTS: In the elders, higher SLS was associated with the recruitment of a network of brain areas involving left anterior cingulate and anterior insula (R² = 0.94; p < 0.0001). Three patients also expressed this network. In the remaining patients, higher SLS was associated with the recruitment of an alternate network consisting of left posterior temporal cortex, calcarine cortex, posterior cingulate, and the vermis (R² = 0.81, p < 0.001). Expression of this network was unrelated to SLS in the elders and more intact AD patients.

CONCLUSIONS: The patients’ use of the alternate network may indicate compensation for processing deficits. The transition from the normal to the alternate network may indicate a point where brain disease has irreversibly altered brain function and thus may have important implications for therapeutic intervention.

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