Among older adults undergoing cardiac surgery, delirium is accompanied by marked increases in circulating TDP-43, offering insights into brain vulnerability and the early biochemical changes that may precede dementia.
According to the findings of a study led by Christopher Simon et al., delirium following cardiac surgery is linked to marked increases in circulating TAR DNA-binding protein 43 (TDP-43) levels, suggesting a potential role for TDP-43 as a prognostic biomarker of acute neurological injury and blood-brain barrier disruption.
With the goal to determine potential associations between postoperative delirium development and severity, serum TDP-43 (nuclear protein essential for transcriptional events) levels were analyzed in patients aged 60 years and older who participated in the Minimizing ICU Neurological Dysfunction with Dexmedetomidine-induced Sleep (MINDDS) clinical trial. Total serum TDP-43 levels, quantified using a single molecule array (Simoa), were compared between preoperative and postoperative day one timepoints, stratified by delirium status as determined by the Confusion Assessment Method (CAM).
To evaluate temporal changes, an independent validation cohort of 25 older adults undergoing major cardiac surgery was also examined. On postoperative day 1, the total serum TDP-43 levels escalated by 16.5% when compared to preoperative levels. This rise was markedly greater in those who developed delirium, with a median increase of 55.1%. These findings remained prominent even after adjusting for intervention group, age, sex, and baseline cognitive performance in multivariable models.
In the validation cohort, TDP-43 levels spiked immediately after cardiopulmonary bypass and gradually declined by the following day. By linking TDP-43 levels to delirium, this research provides novel insights into the mechanisms behind postoperative cognitive decline and highlights the potential for TDP-43 as a prognostic tool for identifying patients at risk for longer-term neurodegenerative ailments.
Brain, Behavior, & Immunity - Health
Elevated TDP-43 serum levels associated with postoperative delirium following major cardiac surgery
Christopher Simon et al.
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