Effect of preoperative transcranial direct current stimulation on postoperative delirium in elderly patients following laparoscopic surgery

Abstract

BACKGROUND

Postoperative delirium (POD), an acute neuropsychiatric complication in elderly surgical patients, manifests as attention and cognitive disturbances that may last 24-72 hours after surgery, potentially progressing to dementia. Transcranial direct current stimulation (tDCS), a non-invasive neuromodulation technique, enhances cortical excitability and cognitive function by modulating brain networks and synaptic plasticity. Elderly patients undergoing major laparoscopic surgery face elevated POD risks due to prolonged anesthesia and pneumoperitoneum-induced cerebral hypoperfusion. This study investigates whether pre-anesthesia tDCS can reduce POD incidence in this population.

AIM

To investigate the effect of preoperative tDCS on reducing the incidence of POD in elderly patients undergoing major laparoscopic surgery.

METHODS

In this study, we enrolled 220 elderly patients who underwent major laparoscopic surgery between April 2024 and December 2024. Patients were randomly assigned to the active-tDCS (group A) and sham-tDCS (group S) groups. A single session of tDCS or sham stimulation was administered 30 minutes before anesthesia induction. The primary outcome was the incidence of POD during within 3 days postoperatively.

RESULTS

A total of 201 patients were included in the final analysis, with 100 patients in group A and 101 in group S. The incidence of POD within 3 days postoperatively was 7.0% in group A, which was significantly lower than 22.8% in group S. On postoperative day 1, the Self-Rating Anxiety Scale and Self-Rating Depression Scale scores significantly differed between the two groups, but the pain scores showed no significant difference.

CONCLUSION

A single session of preoperative tDCS can reduce the incidence of POD in elderly patients undergoing major laparoscopic surgery and can also reduce postoperative anxiety and depression in these patients.

Key Words: Transcranial direct current stimulation; Postoperative delirium; Cognition; Laparoscopic surgery; Randomized controlled trial

Core Tip: A single session of preoperative transcranial direct current stimulation (tDCS) significantly reduces the incidence of postoperative delirium (POD) in elderly patients undergoing major laparoscopic surgery, with a POD rate of 7.0% in the tDCS group compared to 22.8% in the sham group. In addition, tDCS significantly reduces postoperative anxiety and depression but not pain. These findings uphold preoperative tDCS as a promising intervention for preventing POD and enhancing psychological recovery in elderly surgical patients.

INTRODUCTION

Postoperative delirium (POD) is an acute central nervous system syndrome and is a common postoperative complication in elderly patients, often associated with surgical trauma. POD typically occurs in a paroxysmal manner within 24 hours to 72 hours after surgery. It is characterized by disturbances in attention, perception, awareness, cognitive function, and consciousness, with significant fluctuations in both the timing and severity of episodes[1]. In elderly patients, POD can impair cognitive function, and in severe cases, it may directly lead to dementia, with severe implications for patients, their families, and society[2,3]. Therefore, effective prevention of POD is of clinical importance. Current research indicates that nonpharmacological interventions can reduce the incidence of POD[4].

Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique that regulates cortical excitability by applying weak direct current to specific brain areas through two or more electrodes placed on the scalp[5]. Anodal stimulation typically increases cortical excitability, whereas cathodal stimulation decreases it. Research has shown that 15 minutes of tDCS can induce sustained changes in cortical excitability that last over 60 minutes, resulting in improved cognitive and motor functions in healthy elderly individuals[6,7], reduced age-related cognitive decline, and reversal of age-related functional brain activity and connectivity changes[8]. Its mechanisms of action may involve changes at multiple levels[9,10], ranging from cellular processes to the regulation of brain network functions. These include altering cortical excitability[5], improving local cerebral blood flow[11], increasing synaptic plasticity[12], modulating intercortical brain network connectivity[13], and influencing brain neurotransmitters[14].

Older age (≥ 65 years) is an independent risk factor for cognitive decline[15], which can be further exacerbated by surgery and anesthesia. In particular, major laparoscopic surgery is associated with prolonged surgical duration, and the pneumoperitoneum required for it can impair the autoregulatory function of the brain (e.g., blood flow, tissue oxygenation, and regional cerebral oxygen saturation), thereby increasing the incidence of POD[16,17]. Therefore, we aimed to investigate the role of a single session of tDCS before anesthesia induction in reducing the incidence of POD among elderly patients undergoing major laparoscopic surgery.

MATERIALS AND METHODS

Study design

This was a single-center, double-blind, randomized controlled trial conducted at the Affiliated Hospital of Xuzhou Medical University from April 2024 to December 2024. The study protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Xuzhou Medical University, approval No. XYFY2024-KL026-01 and registered with the Chinese Clinical Trial Registry, registration No. ChiCTR2400087975. All participants signed a written informed consent form and voluntarily participated in this study. The study is reported according to the CONSORT statement for nonpharmacological treatment randomized trials.

Study population

The study population included patients aged ≥ 65 years with an American Society of Anesthesiologists (ASA) classification of II or III who were scheduled for elective laparoscopic surgery (with an expected surgery duration of > 2 hours). The following were the exclusion criteria: (1) Patients with severe neurological or psychiatric disorders or those currently taking antipsychotic medications; (2) Patients with cognitive impairment as assessed by the Mini-Mental State Examination (MMSE) (illiterate ≤ 17, primary school ≤ 20, and junior high school and above ≤ 23); (3) Patients with communication difficulties; (4) Patients who refused to sign the informed consent form; (5) Patients with contraindications for tDCS (e.g., intracranial metal foreign bodies and pacemakers); (6) Patients with severe cardiovascular/cerebrovascular diseases or liver/kidney insufficiency; and (7) Patients with preoperative hemoglobin < 7 g/dL.

Patients who were initially included but met any of the following criteria during the course of the study were eliminated from the study: (1) Patients who were postoperatively transferred to the intensive care unit (ICU); (2) Those who withdrew from the study at any assessment stage; and (3) Those whose surgical procedure was altered or who experienced anesthesia or surgical complications (e.g., allergies and massive bleeding). All participants were informed of the overall study process.

Randomization and blinding

Patients were randomly assigned to the active-tDCS group (group A) or the sham-tDCS group (group S) in a 1:1 ratio on the basis of a computer-generated random number sequence. The allocation information was sealed in an envelope, and only the medical staff administering the tDCS were aware of the group assignments. Both patients and the researchers involved in subsequent follow-ups and data analyses were blinded to the group allocation.

Intervention

tDCS was initiated 30 minutes before anesthesia induction. The equipment was provided by Jiangxi Huaheng Jingxing Medical Technology Co. Ltd., model MBM-I, as shown in Supplementary Figure 1. First, saline-soaked sponge electrodes were used, with the anode placed at the F3 region (determined using the 10-20 electroencephalogram electrode placement method) and the cathode placed 1-2 cm above the right eyebrow. Group A patients received a constant current stimulation of 2 mA for 20 minutes, with the current gradually increasing during the first 30 seconds and gradually decreasing during the final 30 seconds. Group S patients did not receive constant current stimulation during the 19-minute middle phase; they were given only the gradual increase during the first 30 seconds and the gradual decrease during the last 30 seconds. In a previous study[18], participants receiving tDCS could not accurately identify whether they were administered real or sham stimulation. This suggests that the inclusion of a sham stimulation group can effectively maintain blinding in double-blind studies. Patients were closely monitored throughout the procedure, and any adverse events were recorded. If necessary, the stimulation could be stopped at any time.

Anesthesia procedure

Anesthesia induction was performed using 0.01 mg/kg midazolam, 0.3 mg/kg etomidate, 0.6 mg/kg rocuronium, and 0.5 μg/kg sufentanil. A bilateral transversus abdominis plane block and rectus sheath block were performed with 40 mL of 0.375% ropivacaine. Intraoperatively, anesthesia was maintained with a propofol infusion at 3-6 mg/(kg × hour), remifentanil infusion at 0.1-0.25 μg/(kg × minute), and sevoflurane at 1%, keeping the bispectral index between 40 and 60. Additional muscle relaxants were given as needed. Intraoperative blood pressure was maintained within 20% of the baseline. Respiratory parameters were set to a tidal volume of 6-8 mL/kg and respiratory rate of 12-16 breaths/minute, and the partial pressure of end tidal carbon dioxide (PetCO₂) was maintained at 35-45 mmHg. The body temperature was kept above 36 °C during the procedure.

Postoperatively, all patients were transferred to the post-anesthesia care unit (PACU) and antagonized with 0.5 mg flumazenil and 2 mg/kg sugammadex sodium. Postoperative pain management was self-administered by patients through patient-controlled intravenous analgesia. The solution comprised 2 μg/kg sufentanil and 6 mg ondansetron and was diluted to 110 mL, with a background dose of 2 mL/hour, a single dose of 0.5 mL, and a lockout interval of 15 minutes. Patients were transferred from the PACU to the ward only when their Steward score was > 4 and they exhibited stable respiratory and circulatory function. After returning to the ward, if the patient’s Numeric Rating Scale (NRS) score was > 6, dezocine was administered intramuscularly as rescue analgesia.

Outcome measures

The primary outcome measure is the incidence of POD within 3 days postoperatively. In the PACU, the Confusion Assessment Method (CAM) for the ICU (CAM-ICU) was used for delirium assessments, whereas in the ward, the CAM was used. The CAM was developed by Inouye et al[19] in the United States on the basis of the diagnostic criteria for delirium in the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised. Its design features make it particularly suitable for use by non-psychiatric clinicians and nursing staff. The CAM-ICU is an adapted version of the CAM with modified attention assessment components. This method shows high sensitivity and specificity, proving to be both reliable and clinically effective[19]. The investigators assessed the patients for delirium at the time of preparations for patients’ transfer back to the ward (T1), in the evening of the day of surgery (T2); the morning (T3) and afternoon (T4) of postoperative day 1; the morning (T5) and afternoon (T6) of postoperative day 2; and the morning (T7) and afternoon (T8) of postoperative day 3. If POD was identified at T8, follow-up was continued for an additional day until the delirium symptoms were resolved. Secondary outcome measures included postoperative pain score (NRS), depression score (Self-Rating Depression Scale), and anxiety score (Self-Rating Anxiety Scale) at T4, along with the recording of rescue analgesia usage, types of POD, length of hospital stay, and any adverse events. During the assessments, the patient’s family members were also interviewed to avoid missing any key information. The study timeline is shown in Supplementary Figure 2.

Sample size calculation

Sample size was calculated using the PASS 15.0 software. Based on previous literature, the incidence of POD in elderly patients undergoing laparoscopic major surgery (surgery time > 2 hours) was 24.8%[20]. Pre-experimental data indicated that the incidence of POD could be reduced to 10% after preoperative tDCS intervention. With a significance level of α = 0.05 and a power of 1-β = 0.8, the required sample size was determined to be 200 patients. Considering a 10% dropout rate, the planned recruitment was 220 patients (n = 110).

Statistical analysis

Statistical analysis was performed using IBM SPSS 27.0 and R 4.4.1 software. Categorical data were expressed as rates and percentages and analyzed using the χ² or Fisher’s exact test. Normally distributed continuous data were presented as mean ± SD and compared between groups using independent samples t-test. Non-normally distributed continuous data were expressed as median and interquartile range and analyzed using the Mann-Whitney U test. The cumulative incidence of POD was analyzed using Kaplan-Meier survival analysis and log-rank test. Logistic regression was used to analyze the risk factors for POD. Subgroup analysis was performed to explore the differences in intervention effects across various subgroups. The mediation effect of depression and anxiety on POD was analyzed using R software. Two-tailed tests were conducted, with α = 0.05. A P value of < 0.05 was considered statistically significant.

RESULTS

Between April 2024 and December 2024, 296 elderly patients scheduled for laparoscopic major surgery were screened. Among them, 48 patients refused to participate, 13 did not meet the inclusion criteria (5 patients had preoperative hemoglobin levels < 7 g/L, 4 patients had severe liver or kidney dysfunction, 3 had preoperative MMSE scores below the standard, and 1 had difficulty communicating), and 15 had canceled their planned operations. Consequently, 220 patients were enrolled in the study and were randomly assigned to group A or group S in a 1:1 ratio. Ten patients in group A were eliminated (7 patients were admitted to the ICU postoperatively and 3 had a change in the surgical procedure), and 9 patients in group S were eliminated (5 were admitted to the ICU postoperatively and 4 had a change in the surgical procedure). Ultimately, 201 patients were included in the final analysis (100 in group A and 101 in group S). The entire study flow is shown in Figure 1.

Figure 1 CONSORT flow chart. tDCS: Transcranial direct current stimulation; ICU: Intensive care unit.

Baseline data and surgical-related information

The baseline data and clinical characteristics of the two groups are shown in Table 1. The two groups did not significantly differ in terms of age, sex distribution, the type of surgery, the ASA classification, preoperative depression score, anxiety score, sleep score, comorbidity index, and frailty score. The groups also did not significantly differ in terms of surgical and anesthesia duration and use of anesthetic drugs (Supplementary Table 1).

Table 1 Baseline characteristics of study participants by treatment group, n (%).

Characteristics	Sham-tDCS (n = 101)	Active-tDCS (n = 100)	P value
Sex			0.332
Male	74 (73.3)	67 (67.0)
Female	27 (26.7)	33 (33.0)
Age (year), median (IQR)	72 (69-76)	72 (69-75)	0.877
BMI (kg/m2), mean ± SD	22.79 ± 2.67	22.43 ± 2.52	0.332
ASA score (%)			0.472
II	81 (80.2)	76 (76.0)
III	20 (19.8)	24 (24.0)
History of smoking	36 (35.6)	40 (40.0)	0.524
History of anesthesia	33 (32.7)	34 (34.0)	0.842
MMSE score, median (IQR)	26 (25-28)	26 (25-28)	0.144
Hemoglobin (g/L), median (IQR)	125 (111.5-139)	123 (115.5-132)	0.680
Albumin (g/L), median (IQR)	39.14 (3.64)	39.25 (3.52)	0.827
Self-Rating Depression Scale, median (IQR)	28 (26-29)	28 (26.25-30)	0.353
Self-Rating Anxiety Scale, median (IQR)	28 (27-30)	28.5 (27-30.75)	0.104
Athens Insomnia Scale, median (IQR)	1 (1-2)	1 (1-2.75)	0.797
Age-adjusted Charlson Comorbidity Index, median (IQR)	3 (3-4)	3 (2-3)	0.327
Education level			0.657
Illiteracy	17 (16.8)	21 (21.0)
Elementary school	45 (44.6)	43 (43.0)
Middle school	28 (27.7)	28 (28.0)
High school	10 (9.9)	7 (7.0)
College graduate	1 (1.0)	1 (1.0)
Frailty			0.204
Robust	46 (45.5)	58 (58.0)
Prefrail	38 (37.6)	30 (30.0)
Frail	17 (16.8)	12 (12.0)
Comorbidities			0.728
Hypertension	40 (39.6)	44 (44.0)
Diabetes	24 (23.8)	19 (19.0)
Stroke	24(23.8)	22 (22.0)
Coronary heart disease	4 (4.0)	5 (5.0)
Type of operation			0.867
Stomach	44 (43.6)	44 (44.0)
Rectum	23 (22.8)	28 (28.0)
Colon	15 (14.9)	11 (11.0)
Liver	13 (12.9)	11 (11.0)
Pancreaticoduodenum	6 (5.9)	6 (6.0)

tDCS: Transcranial direct current stimulation; IQR: Interquartile range; BMI: Body mass index; MMSE: Mini-Mental State Examination; ASA: American Society of Anesthesiologists.

Primary and secondary outcomes

The incidence of POD within 3 days was significantly lower in group A than in group S (7.0% vs 22.8%; relative risk 0.830, 95% confidence interval: 0.737-0.935) (P = 0.002) (Table 2). However, the two groups did not significantly differ regarding the duration of POD (P = 0.432) and the types of delirium (P = 0.829). The groups also did not significantly differ in terms of NRS scores, use of rescue analgesia, or length of hospital stay at the T4 time point. However, anxiety scores (P = 0.045) and depression scores (P = 0.024) differed significantly between the two groups.

Table 2 Postoperative data by treatment group, n (%).

Characteristics	Sham-tDCS (n = 101)	Active-tDCS (n = 100)	P value
Postoperative delirium	23 (22.8)	7 (7.0)	0.002
Days with delirium, median (IQR)	2 (1-2)	2 (1.25-2)	0.432
Type of delirium			0.829
Hypoactive	15	4
Hyperactive	4	1
Mixed	4	2
Self-Rating Anxiety Scale, median (IQR)	27 (24.5-28)	26 (24-27)	0.045
Self-Rating Depression Scale, median (IQR)	27 (26-29)	26 (25-28)	0.024
Numeric Rating Scale score, median (IQR)	4 (3-5)	4 (3-4)	0.243
Use of salvage analgesics	18 (17.8)	14 (14.0)	0.459
Duration of hospitalization, median (IQR), day	14 (12-18)	15 (13-18)	0.445

tDCS: Transcranial direct current stimulation; IQR: Interquartile range.

To compare the incidence of POD at different time points, we used Kaplan-Meier curves to analyze the relationship between the incidence of POD and time in both groups. The overall incidence of POD was significantly lower in group A than in group S (log-rank P = 0.002; hazard ratio = 0.287, 95% confidence interval: 0.140-0.586; Figure 2).

Figure 2 Kaplan-Meier curves of the cumulative incidence of postoperative delirium during postoperative days 1-3 in the active transcranial direct current stimulation and sham stimulation groups. tDCS: Transcranial direct current stimulation; HR: Hazard ratio.

Regression and subgroup analyses

Based on previous research, we included 10 potential factors associated with the occurrence of POD in univariate logistic regression analysis[21,22]. These factors included the intervention group, age, the ASA classification, the MMSE score, the sleep score, smoking history, frailty status, surgery duration, preoperative hemoglobin, and albumin levels. Statistical analysis showed that the P values of the intervention group, age, the MMSE score, frailty status, and preoperative albumin levels were < 0.1. Then, we included these five factors in a multivariate logistic regression and found that the P values of the tDCS intervention, the MMSE score, and frailty status were < 0.05, indicating statistical significance (Table 3).

Table 3 Binary logistic regression analysis was performed to analyze the risk factors of postoperative delirium.

Characteristics	Univariable analysis unadjusted OR (95%CI)	P value	Multivariable analysis adjusted OR (95%CI)	P value
Group	0.255 (0.104-0.627)	0.003	0.284 (0.111-0.727)	0.009
Age	2.889 (1.177-7.089)	0.021	1.994 (0.758-5.241)	0.162
ASA	1.665 (0.701-3.954)	0.248	-	-
MMSE	0.253 (0.098-0.650)	0.004	0.275 (0.102-0.739)	0.010
History of smoking	1.803 (0.826-3.938)	0.139	-	-
FRAIL	3.918 (1.596-9.616)	0.003	2.838 (1.091-7.382)	0.032
Hemoglobin1	1.443 (0.627-3.319)	0.388	-	-
Albumin	0.474 (0.213-1.057)	0.068	0.599 (0.251-1.430)	0.248
AIS	2.000 (0.726-5.512)	0.180	-	-
Duration of surgery	1.686 (0.709-4.009)	0.237	-	-

¹Normal hemoglobin values are 120-160 g/L for adult men and 110-150 g/L for adult women.

The multivariable section in the model only used variables with P < 0.100. Specific subgroups: Age (≤ 65 years vs > 65 years); American Society of Anesthesiologists physical status classification score (II vs III); Mini-Mental State Examination (≤ 26 vs > 26); history of smoking (yes vs no); frailty (robust vs prefrail or frail); hemoglobin (non-anemia vs anemia); albumin (≤ 39 vs > 39); Athens Insomnia Scale (≤ 3 vs > 3); duration of surgery (≤ 180 vs > 180). OR: Odds ratio; CI: Confidence interval; ASA: American Society of Anesthesiologists; MMSE: Mini-Mental State Examination; AIS: Athens Insomnia Scale.

To further explore the efficacy of tDCS under different demographic characteristics, we conducted subgroup analyses incorporating age, the ASA classification, frailty, anemia, albumin, and educational level. The results indicated no significant differences in the therapeutic effects of tDCS across subgroups (Supplementary Figure 3).

Mediation effect analysis

To further explore the potential mechanisms of action of tDCS on POD, we used depression and anxiety scores as mediators in the equation model and conducted mediation effect analysis using R software. Path coefficients for the three variables are shown in Figure 3. tDCS had a direct impact on POD, and neither depression nor anxiety scores served as mediators. Specifically, the mediation effect of anxiety and depression scores accounted for 4.0% and 4.9% of the total effect, respectively (Supplementary Table 2).

Figure 3 Proposed models that investigate mediated effects. A: Depression as a mediating effect; B: Anxiety as a mediating effect. tDCS: Transcranial direct current stimulation; POD: Postoperative delirium.

Adverse events

This study observed the occurrence of complications within 3 days postoperatively. No significant differences were found between group A and group S. In addition, pain at the stimulation site was identified as the most common adverse reaction to tDCS intervention. The incidence of pain at the stimulation site was 15% in group A and 3% in group S, which was a significant difference (P = 0.003; Supplementary Table 3). However, the pain intensity at the stimulation site was mild, well tolerated by patients, and disappeared immediately after the stimulation was completed.

DISCUSSION

POD is among the most common postoperative complications and is particularly prevalent in elderly patients. It can directly impact the cognitive function of elderly patients, increasing the risk of postoperative cognitive dysfunction. The likelihood of developing postoperative cognitive dysfunction is 14 times higher in patients with POD than in those without POD[23]. This study used the noninvasive technique of tDCS, which was administered 30 minutes before general anesthesia induction. The results showed that compared with sham stimulation, tDCS significantly reduced the incidence of POD and reduced depressive and anxious emotions on postoperative day 1 in elderly patients undergoing laparoscopic major surgery.

Previous studies have shown that the occurrence of POD is associated with various factors, such as advanced age, surgical trauma, the ASA classification, and preoperative cognitive status[21,22]. Among these, advanced age is an independent risk factor[15]. Research has found that in elderly patients, the brain volume, cortical thickness, and white matter integrity are reduced and the connectivity of brain functional networks is decreased[24]. Poor baseline cognitive status is a strong predictor of perioperative neurocognitive disorder[25]. Gillis et al[26] suggested that preoperative rehabilitation can enhance preoperative physiological reserves, improve surgical tolerance, and promote postoperative recovery[26]. It has been reported that a single session of tDCS can temporarily reverse age-related cognitive decline and functional brain activity changes[8]. These changes are speculated to result from synaptic plasticity changes[12] and regulation of brain network connectivity caused by tDCS[13], which collectively reduce the incidence of POD in elderly patients undergoing lower limb joint replacement[27]. This finding is consistent with our study wherein a single tDCS intervention performed 30 minutes before anesthesia induction still significantly reduced the incidence of POD in elderly patients undergoing major laparoscopic surgery compared to the control group.

However, subsequent multivariate logistic regression analyses revealed that age was not the key factor influencing the occurrence of POD. We believe the reasons may be as follows: (1) The sample size was small, and specifically, there was minimal age variation among patients, thus, the difference caused by age factors was not significant in statistical analyses; and (2) The effect of age on POD is closely related to the degeneration of the central nervous system, which is reflected in cognitive decline and lower MMSE scores. In this study, MMSE scores were among the key factors influencing the occurrence of POD. Furthermore, our subgroup analysis did not show any interaction effect of tDCS efficacy across different subgroups. However, there may be a potential therapeutic advantage in the subgroup with lower MMSE scores and lower education levels, which needs to be further explored in future trials with larger sample sizes.

It is well-known that elderly patients may experience varying degrees of cognitive decline, and the likelihood and severity of cognitive impairment increase with age[28]. The MMSE is a commonly used clinical tool to assess cognitive function, and lower MMSE scores are typically indicative of cognitive impairment[29]. As previously noted, we identified lower preoperative MMSE scores as a risk factor for POD in this study. We consider that surgical and anesthetic trauma may more easily cause further damage to the already frail central nervous system, even though no significant between-group differences in terms of surgical duration and anesthetic medication were identified in our study.

Gastrointestinal surgery patients are often preoperatively frail, and severe preoperative frailty is closely associated with poor clinical outcomes[30]. Gracie et al[31] suggested that preoperative frailty significantly impacts the occurrence of POD and predicts poorer clinical outcomes. Our results also upheld preoperative frailty as a risk factor for POD.

We also found that the depression and anxiety scores on postoperative day 1 were significantly lower in group A than in group S, which is consistent with previous research[32]. Numerous studies have suggested that depression and anxiety result from an imbalance in the left and right dorsolateral prefrontal cortex (DLPFC) and abnormal functioning of the amygdala[33,34]. In the present study, the anodal stimulation applied to the left DLPFC increased cortical excitability and modulated synaptic plasticity, which may be the potential therapeutic effect[35]. Chen et al[35] suggested that preoperative depression and anxiety states significantly increase the incidence of POD; however, upon including depression and anxiety in the mediation analysis, we found that tDCS reduced the incidence of POD directly and not via lowering depression and anxiety scores.

Previous studies have shown that tDCS can alleviate pain symptoms and improve cognitive function in patients[27,36]. However, we identified no significant differences in NRS scores between the two groups. We speculate that this may be due to insufficient stimulation parameters and inadequate number of stimulations in our study and the fact that all patients had adequate postoperative pain relief. In addition, this could also be related to the stimulation site we selected.

In this study, we chose the left DLPFC as the anodal site for tDCS stimulation. The DLPFC is a key component of the frontoparietal network. It is primarily involved in working memory, attention, and executive function and plays a key role in cognitive differences during aging[37,38]. Specifically, the left DLPFC is mainly responsible for working memory, cognitive flexibility, and memory retrieval. Previous research has confirmed using functional magnetic resonance imaging (fMRI) that anodal tDCS increases the general connectivity of the functional networks related to the target brain regions[39]. Few previous studies have investigated the effects of tDCS on POD. To our knowledge, only Tao et al[27] found that a single session of tDCS, using the same stimulation parameters as used by us in the present study, reduced the incidence of POD. This is our reason behind selecting the left DLPFC as the anodal stimulation target. However, due to experimental limitations, we did not use fMRI to observe the specific effects of tDCS. In the future, we can select different stimulation sites to compare the effects of administering tDCS at various stimulation sites on POD in elderly patients.

This study had several limitations. First, this was a single-center study, and protocols and practices of the center may have influenced the outcomes. In the future, we may perform a multicenter study with a large population. Second, the subjects of this study were elderly patients undergoing laparoscopic surgery lasting > 2 hours, which led to a high incidence of POD. Third, we excluded patients who were transferred to the ICU postoperatively and those whose surgical approach was changed during surgery, which does not reflect the clinical characteristics of the study population and may have impacted the incidence of POD[40]. Fourth, we did not use objective measures like imaging techniques (e.g., fMRI and electroencephalography) and biomarkers to further explore the mechanism of tDCS. Fifth, although POD is most likely to occur within the first 3 days postoperatively, the follow-up period in this study may have missed some outcomes. Sixth, although we maintained the PetCO₂ within the target range of 35-45 mmHg, neither PetCO₂ values nor intra-abdominal pressure were statistically analyzed. This oversight may have resulted in an unaccounted confounding factor.

Although our study shows the potential efficacy of tDCS in reducing POD, we acknowledge the importance of evaluating its clinical feasibility for broader implementation. Regarding operational costs, tDCS devices are relatively affordable compared to other neuromodulation technologies (e.g., transcranial magnetic stimulation or invasive stimulation systems). Moreover, tDCS is characterized by its operational simplicity and portability. The technique can be effectively mastered by non-specialist medical personnel after a brief training, making it particularly suitable for perioperative implementation. We hope that future studies can involve multiple medical institutions, expand the sample size, diversify the types of surgeries, integrate neuroimaging techniques, and further explore the protective effects of tDCS on perioperative cognitive function.

CONCLUSION

We found that a single session of tDCS before surgery can reduce the incidence of POD. This may represent a new noninvasive technique for protecting perioperative cognitive function in elderly patients; however, further clinical trials are needed to validate our conclusions.

ACKNOWLEDGEMENTS

We are thankful to the general surgeons and nursing staff of the Affiliated Hospital of Xuzhou Medical University.