Inflammation and the Vulnerable Brain: Understanding Postoperative Delirium and its Associated Long‐Term Cognitive Outcomes

Background Although growing evidence highlights inflammation as a common biological mechanism of delirium and Alzheimer’s disease (AD), not all individuals with high develop delirium, AD, and/or cognitive decline. Therefore other predisposing factors (e.g., brain vulnerability) likely influence the effect on brain. Method We used Role Inflammation after Surgery for Elders (RISE) study adults aged ≥65 who underwent elective surgery under spinal anesthesia (n = 40), to investigate interaction vulnerability persistent neuronal injury. Brain was examined from preoperative cerebrospinal fluid: 1) amyloid status, 2) ATN classification (ATN+ vs. negative groups [ATN-]). Plasma levels C-reactive protein (CRP), interleukin-6, chitinase 3-like (CHI3L1/YKL-40), previously associated were assigned values 1-4 each marker within sample-based quartiles. For patient, we summed these three markers create an score (range 0-12). Persistent injury, measured using postoperative 1 month (PO1MO) plasma, neurofilament light chain (NfL) glial fibrillary acidic (GFAP). Linear regression models association between stratified by vulnerability. Result On average, participants age 75 years, 65% female, 7% had Charlson scores ≥2. identified x Among amyloid+ patients, those in highest tertile [T3] vs T1 0.16 pg/ml higher GFAP (p<.05); however, among amyloid- no observed. No differences classification, Conclusion The injury differs pathology, suggesting potential value identifying older patients vulnerable adverse outcomes may benefit interventions conditions inflammation.