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Background <p>Postoperative neurocognitive disorder (PND) is characterized by cognitive deficits that emerge after surgery. Although often reversible within weeks or months, PND can persist and lead to significant central dysfunction and an increased risk of dementia. Given that obesity is a chronic low-grade inflammatory condition previously associated with structural and functional brain alterations, we hypothesized and demonstrated that it could be a significant risk factor for PND.</p> Methods <p>We assessed the incidence of PND and cognitive performance in obese individuals undergoing cardiac or orthopedic surgeries. In parallel, we developed a preclinical model combining diet-induced obesity in mice with surgically induced tibial fracture. Pharmacological (ketoprofen), surgical (adipose tissue ablation), and behavioral (calorie restriction) interventions were used to target obesity-associated inflammation.</p> Results <p>Compared with nonobese individuals, obese patients presented a greater incidence of early postoperative cognitive changes and lower cognitive performance (<i>p</i> &lt; 0.009). In mice, the combination of obesity and surgery results in exacerbated signs of PND. Importantly, obesity-related PND in mice was prevented by interventions that reduced central and systemic inflammation.</p> Conclusions <p>These findings identify obesity-driven fat mass and inflammation as strong risk factors for PND for the first time. Targeting obesity-associated inflammatory mechanisms may represent an effective strategy to reduce the incidence of this debilitating postoperative condition.</p> Graphical Abstract <p></p>

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Adipose tissue plays a crucial role in obesity-induced postoperative neurocognitive disorders

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月22日

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  • Clémence Tropis,
  • François Labaste,
  • Marie Sallese,
  • Alizée Dortignac,
  • Ophélie Pereira,
  • Sophie Le Gonidec,
  • Fabrice Ferré,
  • Vincent Pey,
  • Raphaëlle Billerach,
  • Guillaume Bouisset,
  • Lionel Dahan,
  • Philippe Valet,
  • Vincent Minville,
  • Cédric Dray

摘要

Background

Postoperative neurocognitive disorder (PND) is characterized by cognitive deficits that emerge after surgery. Although often reversible within weeks or months, PND can persist and lead to significant central dysfunction and an increased risk of dementia. Given that obesity is a chronic low-grade inflammatory condition previously associated with structural and functional brain alterations, we hypothesized and demonstrated that it could be a significant risk factor for PND.

Methods

We assessed the incidence of PND and cognitive performance in obese individuals undergoing cardiac or orthopedic surgeries. In parallel, we developed a preclinical model combining diet-induced obesity in mice with surgically induced tibial fracture. Pharmacological (ketoprofen), surgical (adipose tissue ablation), and behavioral (calorie restriction) interventions were used to target obesity-associated inflammation.

Results

Compared with nonobese individuals, obese patients presented a greater incidence of early postoperative cognitive changes and lower cognitive performance (p < 0.009). In mice, the combination of obesity and surgery results in exacerbated signs of PND. Importantly, obesity-related PND in mice was prevented by interventions that reduced central and systemic inflammation.

Conclusions

These findings identify obesity-driven fat mass and inflammation as strong risk factors for PND for the first time. Targeting obesity-associated inflammatory mechanisms may represent an effective strategy to reduce the incidence of this debilitating postoperative condition.

Graphical Abstract