Postseptic Cognitive Impairment and Expression of APOE in Peripheral Blood: The Cognition After SepsiS (CASS) Observational Pilot Study

Abstract

Background: Cognitive impairment after sepsis is an important clinical problem. Determinants of postseptic cognitive impairment are not well understood. We thus undertook a systems biology approach to exploring a possible role for apolipoprotein E (APOE) in postseptic cognitive impairment. Design: Prospective, observational cohort. Setting: Intermountain Medical Center, a tertiary referral center in Utah. Patients/Participants: Patients with sepsis admitted to study intensive care units. Interventions: None. Methods: We obtained peripheral blood for deep sequencing of RNA and followed up survivors at 6 months with a battery of cognitive instruments. We defined cognitive impairment based on the 6-month Hayling test of executive function. In our primary analysis, we employed weighted network analysis. Secondarily, we compared variation in gene expression between patients with normal versus impaired cognition. Measurements and Main Results: We enrolled 40 patients, of whom 34 were follow-up eligible and 31 (91%) completed follow-up; 1 patient’s RNA sample was degraded—the final analytic cohort was 30 patients. Mean Hayling test score was 5.8 (standard deviation 1.1), which represented 20% with impaired executive function. The network module containing APOE was dominated by low-expression genes, with no association on primary analysis ( P = .8). Secondary analyses suggested several potential lines of future investigation, including oxidative stress. Conclusions: In this prospective pilot cohort, executive dysfunction affected 1 in 5 survivors of sepsis. The APOE gene was sparsely transcribed in peripheral leukocytes and not associated with cognitive impairment. Future lines of research are suggested.