Cognitive control in early stage Alzheimer's Disease

This proposal tests specific predictions regarding the relationship between cognitive and neurobiological impairments observed in early stage Dementia of the Alzheimer's Type (DAT). These predictions were derived from a neural-network computational model which postulates specific functional roles for the prefrontal cortex in cognitive processes related to the control of thoughts and behavior. A growing literature has suggested that DAT is associated with disturbances in prefrontal function, and with impairments in tasks requiring executive control. However, despite accumulating evidence about these cognitive and neurobiological disturbances in DAT, there is still little understanding of whether or how they are associated. Based on work with our computational model, we propose a specific hypothesis regarding the mechanisms by which the prefrontal cortex influences specific cognitive processes, and how these may breakdown in DAT. In particular, we suggest that the prefrontal cortex subserves the representation and maintenance of task-relevant context. Second, we suggest that the DA system serves to regulate the flow of information into DL-PFC. We further suggest that as a result of prefrontal cortex disturbances in DAT, context information represented cannot be actively sustained and will instead decay over time. These hypotheses lead to specific, detailed, and often counter-intuitive predictions regarding the behavioral performance of DAT patients in cognitive control tasks that rely on the representation and maintenance of context. We propose to investigate these hypotheses in a behavioral study comparing early stage DAT patients with healthy older and younger adults. The study will employ a cognitive task designed and validated to engage prefrontal cortex, and to be sensitive to the processing of context. We predict that compared to healthy older adults, DAT patients will show disproportionate deficits in cognitive control functions. This project promises to generate valuable new empirical data regarding the relationship of cognitive deficits in DAT to underlying neurobiological disturbances, and to significantly advance our theoretical understanding of this process. As such, this project may establish the groundwork for developing powerful new behavioral measures that may eventually have direct clinical applicability.

Washington University Alzheimer's Disease Research Center (ADRC)
NIA P50 AG0 5681-17

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