Abstract Cognitive impairment is characterized by problems with memory, language, thinking or judgment. Despite the tremendous known impact of impaired cognition on quality of life and individuals' health, beside our pilot study; impaired cognitive function associated with sleep timing disruption as its potential mechanisms, has not been objectively investigated in patients with inflammatory and allergic respiratory diseases such as Chronic rhinosinusitis (CRS). Our KL-2 supported studies and preliminary data have shown significant cognitive impairment in CRS patients compared to controls that was associated with sleep disturbance and sleep timing changes. Leveraging experienced gained through my KL2, the overall objectives of this proposed study are to: (1) characterize cognitive function profile in both healthy controls and patients with chronic inflammation in upper airways ; and identify those at risk of impaired cognition; (2) identify the preventable risk factors of cognitive impairment including sleep timing shift, (3) test the hypothesis that serum IL-6 has a role in this process and may serve as a biomarker for cognitive impairment in CRS. We have already recruited 124 individuals (69 CRS and 55 controls) for our pilot data and will plan to recruit additional study subjects and complete the data acquisition for all these cases to perform a case control study of 100 CRS patients and 100 controls. Aim 1 will characterize the cognitive function profile analyzing 6 domains of cognitive function in this case-control study of patients with CRS of varied severity compared to matched healthy controls; and also aims to identify risk factors of cognitive impairment in CRS. The potential risk factors we plan to study include demographics, socioeconomic and CRS-severity factors; and CRS-related comorbidities (atopy, asthma, etc.). Aim 2 focuses to test the hypothesis that a sleep-timing shift is linked to cognitive function impairment in CRS. Objective measurements of sleep timing including 7 days actigraphy and circadian rhythm assessment questionnaires will be performed in above 100 CRS and 100 control patients. A four-step statistical approach in which a series of regression analysis are conducted will be applied to test whether the effect of CRS severity on cognitive function is mediated by sleep. Aim 3 focuses to test the hypothesis that serum IL-6 is a valid biomarker for cognitive impairment in CRS. For this aim serum IL-6 level will be determined and related to cognitive variables in patients, using a multi-variate statistical model. If IL-6 is found to have a significant mediation, then sleep variables will be added in the regression analysis to explore how they work together to affect the association between IL-6 and cognition. Other inflammatory cytokines and soluble IL-6 receptor will also be measured to test related hypotheses.