There is growing recognition that cognitive functioning is markedly impaired in over 1 of 2 survivors of critical illness. However, the nature and """"""""real world"""""""" consequences of this impairment are largely unknown, as research to date has been extremely preliminary and limited in scope. It may be that critical illness affects specific neuropsychological abilities differentially and that the well documented functional decrements observed after critical illness are related to abnormalities in a particular cognitive arena - notably, executive functioning, defined as """"""""a cognitive domain that controls the execution of complex activities of daily living essential for successful higher order functioning."""""""" Preliminary evidence from the work of this candidate suggests that executive abilities are commonly impaired in older ICU survivors, although this has rarely been investigated. The spectre of thousands of ICU survivors with de novo or accelerated executive dysfunction (ExD) is extremely concerning, due to its probable association with independent living, the ability to comprehend and make informed choices regarding care, adherence to medication regimes, and a range of other outcomes. Utilizing an 800 patient prospective cohort investigation, this proposal will qualitatively extend existing work on cognitive outcomes after critical illness by comprehensively investigating ExD, arguably the neuropsychological capacity most relevant to the successful functioning of patients after critical illness. The candidate will characterize the incidence and risk factors for ExD in ICU survivors, while also determining the contributions of key risk factors to the development and progression of ExD. Additionally, he will identify the particular elements of ExD which are association with functional impairment. Through the accomplishment of these goals, he will further current understandings of mechanisms of brain injury following critical illness, identify modifiable risk factors for the development of ExD, and identify the specific and unique cognitive disabilities associated with persistent functional impairment, while laying the groundwork for future interventional studies and the creation of supportive strategies targeting patients at high risk for adverse outcomes. The public health relevance of ExD in ICU survivors is far-reaching and profound, as this domain is believed to contribute substantially and often dramatically to functional difficulties and problems in the successful management of routine daily tasks needed to maintain independence.
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