Different brain networks mediate task performance in normal aging and AD -Defining compensation

Objective: To determine whether the pathologic mechanisms of AD alter the b rain networks subserving performance of a verbal recognition task. Backgrou nd: Functional imaging studies comparing task-related activation in AD pati ents and controls generally have not used network analysis and have not con trolled for task difficulty. Methods: (H2O)-O-15 PET was used to measure re gional cerebral blood flow in 14 patients and 11 healthy elders during the performance of a serial verbal recognition task under two conditions: low d emand, with study list size (SLS) equal to one; and titrated demand, with S LS adjusted so that each subject recognized words at 75% accuracy. The Scal ed Subprofile Model was used to identify networks of regionally covarying a ctivity across these task conditions. Results: In the elders, higher SLS wa s associated with the recruitment of a network of brain areas involving lef t anterior cingulate and anterior insula (R-2 = 0.94; p < 0.0001). Three pa tients also expressed this network. In the remaining patients, higher SLS w as associated with the recruitment of an alternate network consisting of le ft posterior temporal cortex, calcarine cortex, posterior cingulate, and th e vermis (R-2 = 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 def icits. The transition from the normal to the alternate network may indicate a point where brain disease has irreversibly altered brain function and th us may have important implications for therapeutic intervention.