Does Preoperative Cognitive Optimization Improve Postoperative Outcomes in the Elderly?

Perioperative neurocognitive disorder (PND) is a growing concern, affecting several million elderly patients each year in the United States, but strategies for its effective prevention have not yet been established. Humeidan et al. recently demonstrated that preoperative brain exercise resulted in a decrease in postoperative delirium incidence in elderly surgical patients, suggesting the potential of presurgical cognitive optimization to improve postoperative cognitive outcomes. This brief review summarizes the current knowledge regarding preoperative cognitive optimization and highlights landmark studies, as well as current ongoing studies, as the field is rapidly growing. This review further discusses the benefit of cognitive training in non-surgical elderly populations and the role of cognitive training in patients with preexisting cognitive impairment or dementia. The review also examines preclinical evidence in support of cognitive training, which can facilitate understanding of brain plasticity and the pathophysiology of PND. The literature suggests positive impacts of presurgical cognitive optimization, but further studies are encouraged to establish effective cognitive training programs for elderly presurgical patients.

Netrin-1 Ameliorates Postoperative Delirium-Like Behavior in Aged Mice by Suppressing Neuroinflammation and Restoring Impaired Blood-Brain Barrier Permeability

Postoperative delirium (POD) is a common and serious postoperative complication in elderly patients, and its underlying mechanism is elusive and without effective therapy at present. In recent years, the neuroinflammatory hypothesis has been developed in the pathogenesis of POD, in which the damaged blood-brain barrier (BBB) plays an important role. Netrin-1 (NTN-1), an axonal guidance molecule, has been reported to have strong inflammatory regulatory and neuroprotective effects. We applied NTN-1 (45 μg/kg) to aged mice using a POD model with a simple laparotomy to assess their systemic inflammation and neuroinflammation by detecting interleukin-6 (IL-6), interleukin-10 (IL-10), and high mobility group box chromosomal protein-1 (HMGB-1) levels. We also assessed the reactive states of microglia and the permeability of the BBB by detecting cell junction proteins and the leakage of dextran. We found that a single dose of NTN-1 prophylaxis decreased the expression of IL-6 and HMGB-1 and upregulated the expression of IL-10 in the peripheral blood, hippocampus, and prefrontal cortex. Nerin-1 reduced the activation of microglial cells in the hippocampus and prefrontal cortex and improved POD-like behavior. NTN-1 also attenuated the anesthesia/surgery-induced increase in BBB permeability by upregulating the expression of tight junction-associated proteins such as ZO-1, claudin-5, and occludin. These findings confirm the anti-inflammatory and BBB protective effects of NTN-1 in an inflammatory environment in vivo and provide better insights into the pathophysiology and potential treatment of POD.

Effect of general and sub-arachnoid anesthesia on the incidence of postoperative delirium and cognitive impairments in elderly Chinese patients

Purpose: To investigate the effect of general and subarachnoid (spinal) anesthesia on the incidence of postoperative delirium and cognitive impairments in elderly Chinese patients. Methods: Elderly Chinese patients (n = 281) aged 65 – 79 years (mean age = 74.12 ± 4.15 years) who underwent proximal femoral fracture surgery were recruited over a 1-year period for this study. The patients were evaluated using neuropsychological assessment battery (NAB) 24 h before surgery, and on the first day 1 month after surgery. Data on activity of daily living (ADL) (in this case toileting at the time of discharge) were recorded and analyzed. Results: There was no significant difference in the number of patients that developed postoperative delirium between the two anesthesia groups (p > 0.05). Although the trail making test (TMT) scores (parts A and B) were increased on the first day 1 month after surgery, there were no significant differences in NAB results between the two groups (p > 0.05). Patients who received subarachnoid (spinal) anesthesia had significantly higher dependency for toileting at the time of discharge than those who received general anesthesia (p < 0.05). Conclusion: These results show that general and subarachnoid (spinal) anesthesia do not cause postoperative delirium and cognitive dysfunction in elderly Chinese patients who underwent proximal femoral fracture surgery.

KIBRA, MTNR1B, and FKBP5 genotypes are associated with decreased odds of incident delirium in elderly post-surgical patients

Despite the association between cognitive impairment and delirium, little is known about whether genetic differences that confer cognitive resilience also confer resistance to delirium. To investigate whether older adults without postoperative delirium, compared with those with postoperative delirium, are more likely to have specific single nucleotide polymorphisms (SNPs) in the FKBP5, KIBRA, KLOTHO, MTNR1B, and SIRT1 genes known to be associated with cognition or delirium. This prospective nested matched exploratory case–control study included 94 older adults who underwent orthopedic surgery and screened for postoperative delirium. Forty-seven subjects had incident delirium, and 47 age-matched controls were not delirious. The primary study outcome was genotype frequency for the five SNPs. Compared with participants with delirium, those without delirium had higher adjusted odds of KIBRA SNP rs17070145 CT/TT [vs. CC; adjusted odds ratio (aOR) 2.80, 95% confidence interval (CI) 1.03, 7.54; p = 0.04] and MTNR1B SNP rs10830963 CG/GG (vs. CC; aOR 4.14, 95% CI 1.36, 12.59; p = 0.01). FKBP5 SNP rs1360780 CT/TT (vs. CC) demonstrated borderline increased adjusted odds of not developing delirium (aOR 2.51, 95% CI 1.00, 7.34; p = 0.05). Our results highlight the relevance of KIBRA, MTNR1B, and FKBP5 in understanding the complex relationship between delirium, cognition, and sleep, which warrant further study in larger, more diverse populations.

Burst Suppression During General Anesthesia and Postoperative Outcomes: Mini Review

In the last decade, burst suppression has been increasingly studied by many to examine whether it is a mechanism leading to postoperative cognitive impairment. Despite a lack of consensus across trials, the current state of research suggests that electroencephalogram (EEG) burst suppression, duration and EEG emergence trajectory may predict postoperative delirium (POD). A mini literature review regarding evidence about burst suppression impact and susceptibilities was conducted, resulting in conflicting studies. Primarily, studies have used different algorithm values to replace visual burst suppression examination, although many studies have since emerged showing that algorithms underestimate burst suppression duration. As these methods may not be interchangeable with visual analysis of raw data, it is a potential factor for the current heterogeneity between data. Even though additional research trials incorporating the use of raw EEG data are necessary, the data currently show that monitoring with commercial intraoperative EEG machines that use EEG indices to estimate burst suppression may help physicians identify burst suppression and guide anesthetic titration during surgery. These modifications in anesthetics could lead to preventing unfavorable outcomes. Furthermore, some studies suggest that brain age, baseline impairment, and certain medications are risk factors for burst suppression and postoperative delirium. These patient characteristics, in conjunction with intraoperative EEG monitoring, could be used for individualized patient care. Future studies on the feasibility of raw EEG monitoring, new technologies for anesthetic monitoring and titration, and patient-associated risk factors are crucial to our continued understanding of burst suppression and postoperative delirium.