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- W2896843370 abstract "Delirium and Alzheimer's disease (AD) are common causes of late-life cognitive impairment with clear epidemiologic links; however, the pathophysiology underlying these links remains unclear. Apolipoprotein E (APOE) ɛ4, the strongest genetic risk marker for AD, has been widely studied as a potential risk marker for delirium, and recent work in older surgical patients free of dementia indicates that APOE ɛ4 does not confer significantly increased risk of delirium. However, APOE may influence risk of delirium indirectly by modifying the relationship of delirium with other risk factors such as inflammation. We tested whether APOE genotype modifies the established association between inflammatory marker C-reactive protein (CRP) and postoperative delirium. We examined patients without dementia age≥70 undergoing major non-cardiac surgery in the SAGES: Successful AGing after Elective Surgery study. We collected blood, extracted DNA, and performed APOE genotyping using allele specific polymerase chain reaction assays, considering APOE ɛ4 vs. non-ɛ4 carriers. High plasma CRP, measured on postoperative day 2 (POD2) using ELISA, was defined utilizing the highest sample-based quartile (≥234.12 mg/L). Delirium status was determined with daily interviews rating the Confusion Assessment Method, augmented by a validated chart review. We used generalized linear models adjusted for age, sex, surgery type, and stratified by APOE ɛ4 carrier status, to determine whether APOE modifies the association between CRP and delirium. Among the 557 patients (mean age 76.7 [standard deviation 5.2], 58% female, 81% orthopedic), 19% were APOE ɛ4 carriers. Postoperative delirium occurred in 24%. The relationship between CRP and delirium differed by APOE status. Among APOE ɛ4 carriers, we found a strong relationship between high POD2 CRP and delirium (relative risk [RR] (95% confidence interval [CI]: 3.0(1.4-6.7)). In contrast, among APOE ɛ4 non-carriers, high POD2 CRP was not significantly associated with postoperative delirium (RR(95% CI): 1.2(0.8-1.7)). The p-value for the interaction between APOE and CRP on delirium risk was significant at p<.01. APOE ɛ4 carriers may be particularly vulnerable to the increased risk of delirium conferred by post-surgical inflammation (high POD2 CRP). If validated, this increased vulnerability may help to target future interventions for delirium prevention to the most susceptible group." @default.
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- W2896843370 date "2018-07-01" @default.
- W2896843370 modified "2023-10-16" @default.
- W2896843370 title "P2‐142: THE ASSOCIATION BETWEEN C‐REACTIVE PROTEIN AND POSTOPERATIVE DELIRIUM DIFFERS BY APOLIPOPROTEIN E GENOTYPE" @default.
- W2896843370 doi "https://doi.org/10.1016/j.jalz.2018.06.828" @default.
- W2896843370 hasPublicationYear "2018" @default.
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