Prevalence of undiagnosed mild cognitive impairment in elderly patients undergoing thoracic surgery and its relationship with postoperative outcome: a prospective cohort study

Background The prevalence of undiagnosed mild cognitive impairment (MCI) in elderly patients scheduled for thoracic surgery and its association with adverse clinical outcomes is still unproven. Methods We enrolled 170 patients 65 year of age or older who were scheduled for thoracic surgery. 82 males and 88 females with ASA grade II-III. All the elderly patients were tested with Chinese modied version of MoCA preoperatively. According to the test results, they were divided into two groups: group N (MoCA score>25) and group AN (MoCA score ≤ 25). Outcomes included the hospital length of stay (primary outcome), the length of stay in patients with PPCs (LOS-PPCs), the pulmonary complications (atelectasis, pulmonary infection, respiratory failure) and other complications (blood transfusion, chylothorax, new arrhythmia, myocardial infarction and acute cerebral infarction) (secondary outcomes). Data were analyzed using univariate and multivariate analyses. Results Seventy-four of 154 (49%) patients screened positive for probable mild cognitive impairment (MoCA ≤ 25) in the nal analyses. The hospital length of stay and LOS-PPCs in elderly patients with mild cognitive impairment preoperatively were signicantly longer than those with group N (P<0.05). Multivariate stepwise regression showed that preoperative MCI was an independent risk factor for prolonging the hospital length of stay and LOS-PPCs. Patients with a MoCA score less than or equal to 25 were more likely to have a longer hospital length of stay (OR = 2.355, 95% CI =1.137 to 4.877, P=0.021) and LOS-PPCs (OR = 6.867, 95% CI =1.116 to 42.257, P=0.038), but not related to increase the incidence of postoperative pulmonary complications (OR = 0.955, 95% CI =0.280 to 3.254, P=0.941) and other complications (OR = 1.687, 95% CI =0.502 to 5.665, P=0.398) compared to those with a MoCA score greater than 25.


Background
Preoperative assessment of vital organ function is a routine work [1][2][3] , while brain function assessment is not carried out routinely due to limited clinical testing methods [4] . Previous epidemiological surveys showed the prevalence of cognitive impairment in the elderly population is quite high, ranged from 35% to 50% in the population aged ≥65 years have different degrees of cognitive impairment [5][6] . Preoperative cognitive impairment could lead to delicate and persistent cognitive impairment in elderly patients after surgery [7][8][9] . Annie et al [10] have shown that mild cognitive impairment (MCI) is associated with an increased risk of postoperative delirium and severity. Alex et al [11] study also showed that MCI increases the risk of postoperative cognitive dysfunction (POCD) in elderly patients. Postoperative neurocognitive dysfunction (PND) could prolong hospital stay, increase medical expenses, decrease quality of life, and increase morbidity and mortality of elderly patients [5,[12][13] . Impaired cognitive function is a risk factor for perioperative adverse outcome in elderly patients. Focusing on preoperative cognitive function in elderly patients is a signi cant topic. The American College of Surgeons and the American Geriatrics Society have recently published a joint guideline recommending preoperative cognitive function assessment in elderly patients [14] . However, the relationship between MCI screening and postoperative adverse clinical outcomes in elderly patients undergoing thoracic surgery is still unclear.

Criteria for inclusion and exclusion
Elderly patients of ASA I-III grade, aged 65 years and over, who were scheduled to undergo thoracic surgery were selected. Exclusion criteria: (1)Mental disorders such as anxiety, depression, dementia, etc., which have been clearly diagnosed by patients; (2)Uncorrected visual or hearing impairment (unable to see pictures or read or understand instructions);(3) Inability to understand the researchers' speech; (4)Combined with severe cardiovascular and cerebrovascular diseases;(5)Liver and kidney dysfunction, etc., (6)Have been included in other studies.

Preoperative preparations and anesthesia protocol
Elderly patients enrolled in this study were assessed by a trained investigator in a quiet anesthesia preparation room on a Chinese modi ed version of the MoCA scale. According to the results of MoCA Scale (MoCA Test includes memory, attention, orientation, visual space and executive ability, speech ability and other cognitive domain tests, the total score is 30, the length of education is 6-12 years, the total score is + 1, the length of education is less than 6 years, the total score is + 2, the score is less than 25 points as the existence of MCI) ,the patients were divided into N group (MoCA score>25) and AN group (MoCA score≤25) [15] .
Patients were monitored with electrocardiography, non-invasive blood pressure, pulse oximetry, capnography and bispectral index. General Anesthesia was induced with 0.6 μg/kg sufentanil and a target-controlled infusion of propofol set to a plasma concentration of 4 µg/ml, cisatracurium 0.2mg/kg was given to facilitate double-lumen bronchial tube intubation. Propofol administration was adjusted to of 2.5 µg/ml and Cisatracurium adjusted to 0.12 mg/kg/hour, remifentanil adjusted to 0.1 ug/kg/h in the maintenance period. Invasive blood pressure monitoring was achieved by radial artery cannulation (IBP) and right internal jugular central venous catheterization (CVP). Patients were placed in lateral decubitus. Sufentanil5μg was given before skin incision. PCA pump was used in all patients after operation. The drug used in the pump was sufentanil1 ug/kg + dezocine 0.4 mg/kg (diluted to 100 ml saline, continuous dose 2 ml/h, PCA 0.5 ml, locking time 15 minutes).

Measurements
The demographic data of patients and baseline data, including gender, age, ASA grade, BMI, history of hypertension, diabetes, cerebral infarction, radiotherapy and chemotherapy were recorded. The operation time, surgical procedure (VATS/thoracotomy/robotic assisted VATS), type of operation (anatomical lobectomy-segment, lobectomy/non-anatomical lobectomy-wedge resection), type of anesthesia (general anesthesia-GA/general anesthesia combined paravertebral-GA-PA), intraoperative accident (hypoxemiarefers to SpO 2 < 92%, lasting for more than 10 minutes) , total uid volume and the duration from PACU to extubation were also recorded. The primary outcome was the hospital length of stay. Secondary outcomes were the length of stay in patients with PPCs (LOS-PPCs), the pulmonary complications (atelectasis, pulmonary infection, respiratory failure) and other complications (blood transfusion, chylothorax, new arrhythmia, myocardial infarction and acute cerebral infarction). Prolonged hospital stay refers to postoperative hospital stay for more than or equal to 5 days. Postoperative pulmonary complications (PPCs) were de ned according to the European Perioperative Clinical Outcome (EPCO) de nition.

Statistical analysis
SPSS22.0 statistical software (SPSS Inc. Chicago, IL, USA) was used for data processing. The measurement data were expressed as mean ± standard deviation (SD) or median (interquartile range).
Frequency and percentage were used for counting data. Two independent sample t-test was used to compare the continuous variables with normal distribution. Mann-Whitney U-test was used to compare the continuous variables with non-normal distribution. Chi-square test or Fisher exact test were used to compare the counting data. We used Kaplan-Meier estimates for length of stay and LOS-PPCs. Univariate and multivariate analysis of MCI screening predict the risk of length of stay, LOS-PPCs, the incidence of PPCs and other complications after surgery. Covariate p-value<0.1 in univariate analysis was included in multivariate analysis. A p-value < 0.05 was statistically signi cant.
Based on previous clinical studies [16][17] , preoperative MCI increases the hospital length of stay, but whether it increases the incidence of postoperative complications remains unclear. Therefore, the sample size of this study may be more reasonable based on the hospital length of stay. Sample size calculation based on the reference literature [5][6] and pre-test results showed that the incidence of MCI in elderly patients was about 40%, the length of stay after thoracic surgery was about 4±2 days, and the average length of stay in elderly patients with MCI was increased by 1 day, according to =0.05, =0.2. It was estimated that 10% of the missing rate would eventually need to be included in 146 patients.

Results
A total of 170 patients were enrolled in this study, however, fourteen patients were excluded, two patients for lack of follow-up, and 154 patients were included in the nal analyses (Figure1).
There were no signi cant differences in pre-and intraoperative patient characteristics between the two groups ( Table 1).
The hospital length of stay and LOS-PPCs in AN (MoCA score≤25) group were signi cantly longer than those in N (MoCA score>25) group (Figure2-3).
Univariate and multivariate analysis of MCI screening results predict the risk of length of stay and LOS-PPCs. Multivariate stepwise regression analysis showed that patients with a MoCA score less than or equal to 25 were more likely to have a longer hospital length of stay (OR = 2.355, 95% CI = 1.137 to 4.877, P=0.021) and LOS-PPCs (OR = 6.867, 95% CI =1.116 to 42.257, P=0.038). The variables of P < 0.1 in univariate analysis and multivariate stepwise regression analysis are shown in Table 2-3. Univariate and multivariate analysis of MCI screening results predict the risk of the incidence of PPCs and other complications. Multivariate regression analyses showed that patients with a MoCA score less than or equal to 25 were not related to increase the incidence of PPCs (OR = 0.955, 95% CI =0.280 to 3.254, P=0.941) and other complications (OR = 1.687, 95% CI =0.502 to 5.665, P=0.398) compared to those with a MoCA score greater than 25.

Discussion
These data con rm that poor preoperative cognition as assessed by MoCA screening is both prevalent among geriatric patients scheduled for thoracic surgery and predictive of adverse clinical outcomes including a longer hospital stay and LOS-PPCs. In contrast, MCI preoperatively were not associated with the incidence of postoperative pulmonary complications and other complications. Preoperative cognitive risk screening may help identify those at greatest risk for adverse clinical outcomes, so interventions designed to potentially guide and enhance the care can be targeted to those most likely to bene t.
The Chinese modi ed MoCA Scale adopted in this study is mainly used to evaluate MCI in elderly patients, including visual space and executive function, naming, abstraction, memory, attention and orientation. It has high acceptance and credibility [18][19] . The best cut-off point is 25 points, and it has high sensitivity (90%) and speci city (87%) [20] . We used the MoCA scale of the approximate "gold standard" for MCI assessment, and realized that some people who were assessed as MCI before surgery may be normal. That about one in two geriatric patients scheduled for thoracic surgery have probable cognitive impairment preoperatively is not surprising given the same prevalence of cognitive impairment in other clinical studies [5][6][21][22] .In addition, this study is not limited to one type of thoracic surgery (including VATS/thoracotomy/robotic assisted VATS), so our study is applicable to a wider range of elderly patients undergoing elective thoracic surgery.
Preoperative cognitive impairment is a risk factor for postoperative adverse events and hospitalization [23][24][25] . Recent evidence suggests that poor preoperative cognitive function increases the risk of recent postoperative complications and the cost of care. Culley et al. [16] explored that preoperative cognitive scores in elderly patients undergoing elective orthopedic surgery (Mini-Cog score ≤ 2 points) were associated with increased postoperative delirium, length of stay and increased likelihood of nonresidential placement after discharge, but not associated with other complications. Judith et al. [17] evaluated preoperative cognition in elderly patients undergoing elective vascular surgery based on the MoCA scale. The results suggest that low preoperative cognitive scores are independently associated with preoperative vulnerability scores (EFS, Edmonton Frail Scale ≥ 6.5), but not related to postoperative length of stay. And furthermore, Chen et al. [26] used MMSE to evaluate the preoperative cognition of elderly patients who were scheduled to undergo open lobectomy. The results showed that low preoperative cognitive score was related to the risk of pulmonary complications and the length of stay, but not to the cost of hospitalization.
Based on the data from this study, MCI based on MoCA scale preoperatively were more likely to have a longer hospital length of stay (OR = 2.355, 95% CI = 1.137 to 4.877, P=0.021). However, it does not increase the risk of postoperative pulmonary complications and other complications. Therefore, we infer that preoperative MCI does not lead to prolong postoperative hospital stay by increasing postoperative complications, and the possible mechanism is to aggravate PND [5,[10][11][12][13] . Moreover, the sample size of this study based on the hospital length of stay may be one of the reasons for the difference in postoperative complications between the two groups. Finally, we also analyze the relationship between preoperative MCI and the hospital length of stay in patients with PPCs, mainly considering that PPCs is a common complication after thoracic surgery, and directly lead to prolong hospital stay. The results of this study indicate that preoperative MCI could also predict the hospital length of stay in patients with PPCs (OR = 6.867, 95% CI =1.116 to 42.257, P=0.038).
This study also has certain limitations. Although there is no exact "gold standard" for assessing mild cognitive impairment, only a single MoCA scale for preoperative mild cognitive function screening may occur positive. Additionally, this study do not evaluate the postoperative cognitive status of elderly patients, and could not determine the postoperative cognitive changes in elderly patients with MCI before surgery. Of course, the main purpose of this study was to observe the relationship between preoperative cognitive function and non-cognitive adverse clinical outcomes.

Conclusions
This study demonstrates that the prevalence of undiagnosed probably MCI among elderly patients scheduled for thoracic surgery is high (49%) and are not easily recognized by clinicians. Such impairment is associated with a longer hospital stay and LOS-PPCs, while it is not possible to conclude that it is related to the incidence of pulmonary complications and other complications after surgery. Therefore, we should pay more attention to the preoperative cognition of elderly patients, and provide more care for those at high risk to promote rehabilitation during perioperative.     Preoperative mild cognitive impairment predicts the length of stay Preoperative mild cognitive impairment predicts the length of stay in patients with PPCs