Elevated TDP-43 serum levels associated with postoperative delirium following major cardiac surgery

Topic: Brain proteins, microglia and lab models

Total serum TDP-43 levels increased by 16.5% (95% CI: 5.9%-27.9%, p = 0.0021) on postoperative day one compared to baseline levels. This increase was more pronounced in patients who experienced delirium (median increase of 55.1%, 95% CI: 22.9%-96.4%, p = 0.0002). Further, these findings were conserved in multiple logistic regression models adjusting for treatment, age, sex, and baseline cognitive scores. In the validation cohort, TDP-43 levels were found to be significantly elevated immediately following cardiopulmonary bypass from the baseline, with a gradual decrease by postoperative day one. Our findings demonstrate that post-cardiac surgery delirium among vulnerable patients is associated with significant elevations in circulating TDP-43. This relationship suggests that TDP-43 may serve as a prognostic biomarker for acute neurological insults and blood-brain barrier integrity following cardiac surgery. Overall, our results provide mechanistic insights into the inter-relationship between postoperative delirium and subsequent cognitive impairment, potentially offering new avenues for early intervention in at-risk surgical patients.

@article{simon2025-40134937,
  author  = {Simon, Christopher and Graves, Occam Kelly and Akeju, Oluwaseun and McKay, Tina B.},
  title   = {{Elevated TDP-43 serum levels associated with postoperative delirium following major cardiac surgery}},
  journal = {Brain Behavior \& Immunity - Health},
  year    = {2025},
  doi     = {10.1016/j.bbih.2025.100974},
  pmid    = {40134937},
  url     = {https://doi.org/10.1016/j.bbih.2025.100974}
}

Key findings

• Total serum TDP-43 levels increased by 16.5% (95% CI: 5.9%-27.9%, p = 0.0021) on postoperative day one compared to baseline levels.
• This increase was more pronounced in patients who experienced delirium (median increase of 55.1%, 95% CI: 22.9%-96.4%, p = 0.0002).
• Further, these findings were conserved in multiple logistic regression models adjusting for treatment, age, sex, and baseline cognitive scores.
• In the validation cohort, TDP-43 levels were found to be significantly elevated immediately following cardiopulmonary bypass from the baseline, with a gradual decrease by postoperative day one.
• Our findings demonstrate that post-cardiac surgery delirium among vulnerable patients is associated with significant elevations in circulating TDP-43.

Why it matters

In patients having major cardiac surgery, total serum TDP-43 levels rose after the operation, and the rise was larger in those who developed postoperative delirium. The authors suggest TDP-43 may serve as a prognostic biomarker for acute neurological injury and blood-brain barrier integrity after cardiac surgery.

Study details

• Participants25
• Effect sizeincreased by 16.5%; 5.9%; 27.9%
• Evidence strengthModerate

Read the original

• DOI: 10.1016/j.bbih.2025.100974
• PubMed: 40134937
• Original source →
• Free full text: Brain Behavior & Immunity - Health →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Delirium is a strong risk factor for dementia in the oldest-old: a population-based cohort study Brain : a journal of neurology · 2012-08-09 · usefulness score 64/100 · How common it is
• The inter-relationship between delirium and dementia: the importance of delirium prevention Nature reviews. Neurology · 2022-08-26 · usefulness score 59/100 · Prevention and risk
• The interface between delirium and dementia in elderly adults The Lancet. Neurology · 2015-06-29 · usefulness score 56/100 · Prevention and risk

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