Cerebrospinal Fluid Proteome Changes in Older Non-Cardiac Surgical Patients with Postoperative Cognitive Dysfunction.

Journal Article (Journal Article)

BACKGROUND: Postoperative cognitive dysfunction (POCD), a syndrome of cognitive deficits occurring 1-12 months after surgery primarily in older patients, is associated with poor postoperative outcomes. POCD is hypothesized to result from neuroinflammation; however, the pathways involved remain unclear. Unbiased proteomic analyses have been used to identify neuroinflammatory pathways in multiple neurologic diseases and syndromes but have not yet been applied to POCD. OBJECTIVE: To utilize unbiased mass spectrometry-based proteomics to identify potential neuroinflammatory pathways underlying POCD. METHODS: Unbiased LC-MS/MS proteomics was performed on immunodepleted cerebrospinal fluid (CSF) samples obtained before, 24 hours after, and 6 weeks after major non-cardiac surgery in older adults who did (n = 8) or did not develop POCD (n = 6). Linear mixed models were used to select peptides and proteins with intensity differences for pathway analysis. RESULTS: Mass spectrometry quantified 8,258 peptides from 1,222 proteins in > 50%of patient samples at all three time points. Twelve peptides from 11 proteins showed differences in expression over time between patients with versus withoutPOCD (q < 0.05), including proteins previously implicated in neurodegenerative disease pathophysiology. Additionally, 283 peptides from 182 proteins were identified with trend-level differences (q < 0.25) in expression over time between these groups. Among these, pathway analysis revealed that 50 were from 17 proteins mapping to complement and coagulation pathways (q = 2.44*10-13). CONCLUSION: These data demonstrate the feasibility of performing unbiased mass spectrometry on perioperative CSF samples to identify pathways associated with POCD. Additionally, they provide hypothesis-generating evidence for CSF complement and coagulation pathway changes in patients with POCD.

Full Text

Duke Authors

Cited Authors

  • VanDusen, KW; Li, Y-J; Cai, V; Hall, A; Hiles, S; Thompson, JW; Moseley, MA; Cooter, M; Acker, L; Levy, JH; Ghadimi, K; Quiñones, QJ; Devinney, MJ; Chung, S; Terrando, N; Moretti, EW; Browndyke, JN; Mathew, JP; Berger, M; MADCO-PC Investigators,

Published Date

  • 2021

Published In

Volume / Issue

  • 80 / 3

Start / End Page

  • 1281 - 1297

PubMed ID

  • 33682719

Pubmed Central ID

  • PMC8052629

Electronic International Standard Serial Number (EISSN)

  • 1875-8908

Digital Object Identifier (DOI)

  • 10.3233/JAD-201544

Language

  • eng

Conference Location

  • Netherlands