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Article

Preexisting Dementia Is Associated with Increased Risks of Mortality and Morbidity Following Major Surgery: A Nationwide Propensity Score Matching Study

by
Yu-Ming Wu
1,2,
Hsien-Cheng Kuo
1,2,
Chun-Cheng Li
1,2,
Hsiang-Ling Wu
3,4,
Jui-Tai Chen
1,2,
Yih-Giun Cherng
1,2,
Tzeng-Ji Chen
4,5,
Ying-Xiu Dai
4,6,
Hsin-Yi Liu
1,2 and
Ying-Hsuan Tai
1,2,*
1
Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
2
Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
3
Department of Anesthesiology, Taipei Veterans General Hospital, Taipei 11217, Taiwan
4
School of Medicine, National Yang-Ming University, Taipei 11217, Taiwan
5
Department of Family Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
6
Department of Dermatology, Taipei Veterans General Hospital, Taipei 11217, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2020, 17(22), 8431; https://doi.org/10.3390/ijerph17228431
Submission received: 14 September 2020 / Revised: 12 November 2020 / Accepted: 12 November 2020 / Published: 14 November 2020
(This article belongs to the Section Public Health Statistics and Risk Assessment)
Browse Figure
Versions Notes

Abstract

:
Patients with dementia are predisposed to multiple physiological abnormalities. It is uncertain if dementia associates with higher rates of perioperative mortality and morbidity. We used reimbursement claims data of Taiwan’s National Health Insurance and conducted propensity score matching analyses to evaluate the risk of mortality and major complications in patients with or without dementia undergoing major surgery between 2004 and 2013. We applied multivariable logistic regressions to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for the outcome of interest. After matching to demographic and clinical covariates, 7863 matched pairs were selected for analysis. Dementia was significantly associated with greater risks of 30-day in-hospital mortality (aOR: 1.71, 95% CI: 1.09–2.70), pneumonia (aOR: 1.48, 95% CI: 1.16–1.88), urinary tract infection (aOR: 1.59, 95% CI: 1.30–1.96), and sepsis (OR: 1.77, 95% CI: 1.34–2.34) compared to non-dementia controls. The mortality risk in dementia patients was attenuated but persisted over time, 180 days (aOR: 1.49, 95% CI: 1.23–1.81) and 365 days (aOR: 1.52, 95% CI: 1.30–1.78) after surgery. Additionally, patients with dementia were more likely to receive blood transfusion (aOR: 1.32, 95% CI: 1.11–1.58) and to need intensive care (aOR: 1.40, 95% CI: 1.12–1.76) compared to non-dementia controls. Senile dementia and Alzheimer’s disease were independently associated with higher rates of perioperative mortality and complications, but vascular dementia was not affected. We found that preexisting dementia was associated with mortality and morbidity after major surgery.

1. Introduction

The latest global estimate shows that dementia is a leading global epidemic, affecting approximately 47 million individuals worldwide [1]. Dementia leads to dependence, impaired quality of life, institutionalization, and mortality, which causes a growing and substantial burden of disease in the aging population [1]. Epidemiologic study has reported that the number of people affected by dementia is expected to increase to 131 million by 2050 [2]. Given this demographic trend, we can expect a growing number of dementia patients undergoing surgery in the future. Dementia patients undergoing surgery experience readmission more commonly and generally have longer lengths of hospital stay compared to those without dementia [3], which poses a serious challenge to the healthcare system in perioperative care.
In addition to memory loss and cognitive decline, patients with advanced dementia are predisposed to specific physiological abnormalities, including dysphagia, weight loss, wasting syndrome, susceptibility to infection, and sensory abnormality [4,5]. These pathologies may potentiate a higher perioperative risk of mortality and morbidity in the setting of major surgery. However, whether dementia associates with higher rates of perioperative mortality and morbidity remains uncertain due to several study limitations in previous reports, including small sample size [6,7,8,9], mixed groups of different dementia subtypes [6,7,8,9,10,11], inadequate consideration for confounding factors [8], disadvantages of unmatched statistical methodology [6,7,8,9,10,11], and restriction to specific types of surgery [7,8,10,11] or hospitals [6,7,8,9]. Clarifying the impact of dementia on perioperative risk is of great value to risk stratification and optimal care for this susceptible population.
Accordingly, we conducted a nationwide population-based cohort study to evaluate the risk of mortality and morbidity in patients with dementia undergoing major surgery. Based on the evidence of prior studies [6,7,8,9,10,11], we hypothesized that preexisting dementia is associated with greater risks of all-cause in-hospital mortality and complications after major surgery.

2. Materials and Methods

2.1. Source of Data

We obtained approval from the Institutional Review Boards of Taipei Veterans General Hospital and Taipei Medical University in Taiwan (TMU-JIRB-N202010042 and IRB-TPEVGH-2013-04-005E). Written informed consent was waived by the Institutional Review Board. The Taiwan National Health Insurance program was established in March 1995 and covered more than 99% of 23.4 million Taiwanese residents at the end of 2013. The National Health Insurance (NHI) research database contains comprehensive data of the insured individuals, including demographic characteristics (date of birth, sex, and residential location) and claims data (outpatient and inpatient care, physicians’ primary and secondary diagnoses, prescriptions, treatment procedures, and medical expenditures) [12,13,14,15,16,17].

2.2. Study Design

We utilized three Longitudinal Health Insurance Databases (LHID2000, LHID2005, and LHID2010) which randomly sampled 1 million beneficiaries from the original NHI research database in the years 2000, 2005, and 2010, respectively. The LHIDs contain the most updated medical claims of sampled subjects since 1997. The representativeness of LHIDs has been validated by Taiwan’s National Health Research Institutes [18]. We selected individuals aged more than 20 years who underwent a first major surgery requiring hospitalization for ≥2 days between January 2004 and November 2013 to identify patients with a history of dementia within 24 months prior to the index surgery. Each patient with dementia was randomly matched to a surgical patient without a history of dementia, using a frequency matched pair procedure (case–control ratio, 1:1) to adjust for age, sex, income, coexisting diseases, types of surgery, types of anesthesia, and number of hospitalizations and emergency visits within 24 months prior to the index surgery. We compared the risk of postoperative mortality and morbidity after the index surgery between patients with and without preexisting dementia.

2.3. Ascertainment of Dementia

We identified patients with dementia using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes. This includes senile dementia (ICD-9-CM 290.0-290.3), vascular dementia (ICD-9-CM 290.4), Alzheimer’s disease (ICD-9-CM 331.0), and other subtypes of dementia (ICD-9-CM 294.1) [17]. The diagnoses of dementia were made at least 2 times by board-certified neurologists or psychiatrists. We also evaluated the medications for dementia (i.e., cholinesterase inhibitors or N-methyl-d-aspartate (NMDA) receptor antagonists) within 24 months prior to the index surgery, including donepezil, galantamine, rivastigmine, and memantine [19]. In Taiwan’s NHI regulations, treatment for dementia is reimbursable only after comprehensive laboratory and imaging studies to exclude neurocognitive impairments from other etiologies, including vitamin B12 deficiency, thyroid disease, or cerebrovascular disease.

2.4. Covariate and Outcome Measurement

We used the ICD-9-CM codes of physicians’ diagnoses within 24 months prior to surgery to identify the history of the following coexisting diseases, chosen based on data availability, physiological plausibility, and the existing literature: hypertension, diabetes mellitus, ischemic heart disease, atherosclerosis, cardiac dysrhythmias, heart failure, liver cirrhosis, chronic obstructive pulmonary diseases, chronic kidney disease, cerebrovascular disease, Parkinson’s disease, malignancies, sarcopenia, and obesity. (Supplementary Material) Monthly premium was classified into $0–$500, $501–$800, and >$800 United States dollars (USD).
The primary outcome was 30-day all-cause in-hospital mortality, which was chosen based on a wide range of historical surgical disciplines [20] and data availability [18]. However, to measure long-term outcomes of dementia patients following surgery, we also analyzed 180-day and 365-day all-cause in-hospital mortality in this study. Secondary outcomes were determined from medical claims that occurred within 30 days after index admission, including pneumonia, urinary tract infection, pyelonephritis, surgical site infection, sepsis, acute myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis, cardiac dysrhythmias, acute renal failure, and postoperative bleeding. The NHI research database has been widely validated to evaluate the validity of diagnosis codes and to develop study methodologies, including pneumonia [21], acute myocardial infarction [22], and ischemic stroke [23]. We also collected data about the requirements for blood transfusion [24,25,26] and intensive care during the index surgical admission.

2.5. Statistical Analysis

We conducted matching procedures with propensity score to balance the distribution of age, sex, monthly premium, coexisting diseases, and numbers of emergency visits and hospitalizations within 24 months before surgery between surgical patients with and without dementia. A non-parsimonious multivariable logistic regression model was applied to estimate a propensity score for subjects with or without dementia. We matched dementia subjects to non-dementia controls using a greedy matching algorithm without replacement and within a tolerance limit of 0.05 [27]. Categorical variables were summarized using frequency (percentage), and continuous variables were summarized using mean ± standard deviation or median (interquartile range). The distributions of baseline characteristics in propensity-score-matched samples were compared between subjects with and without dementia by using standardized difference [28]. In this study, we defined perioperative risk as the rate, proportion, or probability of mortality and complications listed in Section 2.4 for dementia patients and controls. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of postoperative mortality and complications were calculated by multivariable logistic regressions. Sensitivity analyses were performed to avoid possible collapsibility bias and multicollinearity from the propensity score matching algorithm, including exclusions of subjects who had dementia diagnosis <1 year before surgery, who underwent cardiovascular surgery, or who were diagnosed with any type of cancer before surgery. We also conducted stratified analyses by age, sex, subtypes of dementia, uses of dementia medication, duration of dementia diagnosis before surgery, and types of anesthesia to examine perioperative risk among patients with dementia within these strata. We considered a two-sided level of 0.05 statistically significant. All statistical analyses were conducted using Statistics Analysis System (SAS), version 9.4 (SAS Institute Inc., Cary, NC, USA).

3. Results

After the matching process, a total of 7863 matched pairs were included for multivariable logistic analyses (Figure 1). Table 1 shows the baseline characteristics of the included subjects with and without dementia. The distributions of demographics, coexisting diseases, types of surgery, and anesthesia were well balanced after propensity score matching. The duration of dementia diagnosis before surgery was median 2.3 years (interquartile range 1.0–4.3 years). Among the dementia subjects, 696 (8.9%) of them received reimbursable medications for dementia and 55 (0.7%) and 4 (0.1%) used two and three types of dementia medications within 24 months before surgery, respectively.

3.1. Risk of Postoperative Mortality and Morbidity

There were 52 (0.7%) and 30 (0.4%) in-hospital deaths that occurred within 30 days after surgery in dementia subjects and non-dementia controls, respectively. After adjusting for covariates, preexisting dementia was significantly associated with 30-day in-hospital mortality (aOR: 1.71, 95% CI: 1.09–2.70) compared to non-dementia controls. (Table 2) Sensitivity analyses demonstrated similar results. (Table 3) Dementia was also associated with higher risks of 180-day (aOR: 1.49, 95% CI: 1.23–1.81) and 365-day all-cause in-hospital mortality (aOR: 1.52, 95% CI: 1.30–1.78) after surgery.
Dementia was also significantly associated with greater risks of pneumonia (aOR: 1.48, 95% CI: 1.16–1.88), urinary tract infection (aOR: 1.59, 95% CI: 1.30–1.96), and sepsis (aOR: 1.77, 95% CI: 1.34–2.34) compared to non-dementia controls. Additionally, patients with dementia were more likely to receive blood transfusion (aOR: 1.32, 95% CI: 1.11–1.58) and to need intensive care (aOR: 1.40, 95% CI: 1.12–1.76). (Table 2).

3.2. Stratified Analyses by Age, Sex, and Subtypes of Dementia

Table 4 shows the results of perioperative risk among patients with dementia, stratified by age, sex, subtypes of dementia, uses of dementia medications, duration of dementia diagnosis, and types of anesthesia. The perioperative risk associated with dementia was significant in subjects with age ≥65 years (aOR: 1.26, 95% CI: 1.13–1.40) and female (aOR: 1.35, 95% CI: 1.16–1.56). As for dementia subtype, senile dementia and Alzheimer’s dementia were both associated with higher perioperative risk, aOR: 1.27 (95% CI: 1.14–1.42) and aOR: 1.45 (95% CI: 1.07–1.96), respectively. The perioperative risk was consistently increased in dementia patients receiving general anesthesia (aOR: 1.28, 95% CI: 1.11–1.47) and regional anesthesia (aOR: 1.32, 95% CI: 1.09–1.60).

4. Discussion

This study discovered that dementia is independently associated with higher risks of 30-day in-hospital mortality, pneumonia, urinary tract infection, and sepsis following major surgery compared to non-dementia controls. In addition, patients with dementia were prone to blood transfusion and admission to intensive care during their surgical hospitalizations. As for subtype of dementia, we found that senile dementia and Alzheimer’s disease but not vascular dementia are linked to mortality and morbidity following major surgery.
Our results were based on a nationwide dataset and covered various types of surgery. In contrast, most prior studies restricted the study population to single hospital [6,7,8,9] and orthopedic [7,10,11] or vascular surgery [8], which made it difficult to generalize their results to institutions with different settings or other types of surgery. Our analyses have taken the subtypes and medications of dementia into account and implemented propensity score matching to best control for potential confounding effects, which was lacking in previous studies [6,7,8,9,10,11]. We observed a significantly higher risk of 30-day all-cause in-hospital mortality, in line with prior studies [6,7,8,9,10]. The increased risk of mortality associated with dementia was attenuated over time but persisted for 180 and 365 days after surgery, which has not been reported previously [6,7,8,9,10,11]. This finding suggests that preexisting dementia adversely impacts both short-term and long-term recovery after major surgery and that its disease burden is not merely limited to postoperative critical care but also to extended care facilities [10,29]. In addition, we also found that the rate of infection (e.g., pneumonia, urinary tract infection, and sepsis) but not thromboembolism (e.g. myocardial infarction and stroke) was significantly increased in dementia patients, in agreement with previous studies [9,11]. Of note, our study first demonstrated a higher likelihood of blood transfusion and intensive care in dementia patients. Studies have shown that dementia is a risk factor for development of perioperative delirium and vice versa [9,30]. In addition to dementia, unrecognized mild cognitive impairment was common in elderly people awaiting surgery [31]. The insult of major surgery may accelerate the progression of cognitive decline in this population [32]. Occurrence of perioperative delirium is an established predictor for both physical and cognitive morbidity after surgery [30,33]. Furthermore, delirium is an exceedingly costly complication, both to patients and to medical facilities. The occurrence of postoperative delirium significantly increases healthcare costs by an estimated 3000 to 10,000 USD additional cost per case [34,35]. The relationship between anesthesia and delirium is not yet fully elucidated. It remains controversial if anesthetic technique and monitoring are correlated with perioperative delirium [36,37,38,39,40]. Some studies claimed that the light depth of sedation and regional anesthesia are effective in preventing postoperative delirium [36,37]. However, a recent randomized trial showed that electroencephalogram-guided anesthetic administration did not reduce the incidence of postoperative delirium among elderly patients [38]. Besides, there is no adequate evidence supporting that the type of anesthesia affects postoperative delirium [39]. Regarding postoperative sedation, Djaiani and colleagues demonstrated that dexmedetomidine sedation decreased incidence and duration of delirium in older patients undergoing cardiac surgery compared to propofol [40]. Future studies are warranted to develop strategies to prevent perioperative delirium and its adverse effect on dementia patients.
We raised three possible explanations for the greater mortality and morbidity associated with dementia. First, dementia is closely linked to immune dysfunction and systemic inflammation, especially in Alzheimer’s disease [41,42]. Patients with advanced dementia are susceptible to infection and have a higher risk of infection-associated death [4,5,43]. Second, Alzheimer’s disease is a strong risk factor for anemia and vice versa [44,45]. This may predispose dementia patients to perioperative use of blood transfusion. Third, dementia is associated with impaired lung function and lung disease [46], which may increase the risk of respiratory complications and the need for intensive care following major surgery.
Importantly, our stratified analyses indicated that dementia of vascular origin does not produce an additional risk of postoperative mortality and morbidity compared to non-dementia counterparts. People with vascular dementia decline in their functional abilities at a slower rate compared to those with Alzheimer’s disease [47]. The better general health condition of subjects with vascular dementia might decrease the perioperative risk. Additionally, a study has reported that pneumonia-caused death was higher in Alzheimer’s disease compared to vascular dementia [48], suggesting a potential difference in patients’ respiratory and immune functions among distinct subtypes of dementia. The development of vascular dementia is closely associated with atherosclerosis and cardiovascular diseases (e.g., hypertension and cerebrovascular disease) [49,50], and these vascular risk factors have been largely controlled in our statistical analyses. Our findings highlight that the subtype of dementia should be taken into consideration in risk stratification for dementia patients undergoing surgery.
There are limitations to our study. First, our data did not contain information about physical measures, biochemical laboratory measures, detailed surgical and anesthetic procedures, perioperative medications, and physicians’ personal skills that were not covered by the NHI database. Therefore, we could not further adjust for cardiac and pulmonary functions; perioperative uses of antibiotics, immunosuppressants, and anti-thrombin therapy; serum hemoglobin level; and surgical blood loss, which might affect the occurrence of mortality, infection, and thromboembolism and the need for blood transfusions after surgery. Second, functional ability and nutritional status of included subjects were unknown in our study, which might also influence the survival of dementia patients [51,52]. Third, we could not differentiate between early and advanced dementia. Fourth, we could not evaluate the relationship between dementia and postoperative delirium due to data unavailability. Finally, residual confound is possible although our analyses have adjusted for a variety of potential confounding factors.

5. Conclusions

We found that preexisting dementia was independently associated with mortality and morbidity after major surgery compared to non-dementia controls. The higher risk of mortality in dementia patients persisted for at least one year after surgery. Senile dementia and Alzheimer’s disease were associated with higher perioperative risk, but vascular dementia was not affected. Patients with dementia clearly require careful preoperative screening and tailored postoperative interventions to improve recovery after surgery. Our results highlight the need to further develop strategies of risk stratification and optimal perioperative care for this susceptible population.

Supplementary Materials

The following are available online at https://www.mdpi.com/1660-4601/17/22/8431/s1, ICD-9-CM codes of comorbidity and outcome.

Author Contributions

Y.-M.W.: manuscript preparation; H.-C.K.: quality control of data and manuscript editing; C.-C.L.: manuscript revision; H.-L.W.: study conceptualization; J.-T.C.: manuscript revision; Y.-G.C.: manuscript revision; T.-J.C.: data acquisition; Y.-X.D.: data acquisition; H.-Y.L.: manuscript editing, result interpretation, and manuscript revision; Y.-H.T.: formal analysis, result interpretation, manuscript revision, and final approval of the version to be published. H.-Y.L. has equal contribution with the corresponding author. All authors have read and approved the final manuscript.

Funding

This work was supported by the grants from Shuang Ho Hospital (109IIT-02), Taipei Medical University, New Taipei City, Taiwan and from the Ministry of Science and Technology (MOST109-2314-B-038-024), Taipei, Taiwan.

Acknowledgments

The authors thank Chien-Chang Liao (Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan) for his kind assistance in the study design.

Conflicts of Interest

There is no financial or other relationship that might lead to a conflict of interest regarding this article to disclose.

References

  1. Ponjoan, A.; Garre-Olmo, J.; Blanch, J.; Fages, E.; Alves-Cabratosa, L.; Martí-Lluch, R.; Comas-Cufí, M.; Parramon, D.; Garcia-Gil, M.; Ramos, R. Epidemiology of dementia: Prevalence and incidence estimates using validated electronic health records from primary care. Clin. Epidemiol. 2019, 11, 217–228. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  2. Martin Prince, A.; Wimo, A.; Guerchet, M. World Alzheimer Report 2015: The Global Impact of Dementia an Analysis of Prevalence, Incidence, Cost and Trends; Alzheimer’s Disease International: London, UK, 2015. [Google Scholar]
  3. White, S.; Griffiths, R.; Baxter, M.; Beanland, T.; Cross, J.; Dhesi, J.; Docherty, A.B.; Foo, I.; Jolly, G.; Jones, J.; et al. Guidelines for the peri-operative care of people with dementia: Guidelines from the Association of Anaesthetists. Anaesthesia 2019, 74, 357–372. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  4. Mitchell, S.L.; Teno, J.M.; Kiely, D.K.; Shaffer, M.L.; Jones, R.N.; Prigerson, H.G.; Volicer, L.; Givens, J.L.; Hamel, M.B. The clinical course of advanced dementia. N. Engl. J. Med. 2009, 361, 1529–1538. [Google Scholar] [CrossRef] [PubMed]
  5. Minaglia, C.; Giannotti, C.; Boccardi, V.; Mecocci, P.; Serafini, G.; Odetti, P.; Monacelli, F. Cachexia and advanced dementia. J. Cachexia Sarcopenia Muscle 2019, 10, 263–277. [Google Scholar] [CrossRef] [PubMed]
  6. Bernstein, G.M.; Offenbartl, S.K. Adverse surgical outcomes among patients with cognitive impairments. Am. Surg. 1991, 57, 682–690. [Google Scholar]
  7. Khan, M.A.; Hossain, F.S.; Ahmed, I.; Muthukumar, N.; Mohsen, A. Predictors of early mortality after hip fracture surgery. Int. Orthop. 2013, 37, 2119–2124. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  8. Steunenberg, S.L.; Te Slaa, A.; Ho, G.H.; Veen, E.J.; de Groot, H.G.W.; van der Laan, L. Dementia in patients suffering from critical limb ischemia. Ann. Vasc. Surg. 2017, 38, 268–273. [Google Scholar] [CrossRef]
  9. Kassahun, W.T. The effects of pre-existing dementia on surgical outcomes in emergent and nonemergent general surgical procedures: Assessing differences in surgical risk with dementia. BMC. Geriatr. 2018, 18, 153. [Google Scholar] [CrossRef] [Green Version]
  10. Seitz, D.P.; Gill, S.S.; Gruneir, A.; Austin, P.C.; Anderson, G.M.; Bell, C.M.; Rochon, P.A. Effects of dementia on postoperative outcomes of older adults with hip fractures: A population-based study. J. Am. Med. Dir. Assoc. 2014, 15, 334–341. [Google Scholar] [CrossRef]
  11. Tsuda, Y.; Yasunaga, H.; Horiguchi, H.; Ogawa, S.; Kawano, H.; Tanaka, S. Association between dementia and postoperative complications after hip fracture surgery in the elderly: Analysis of 87,654 patients using a national administrative database. Arch. Orthop. Trauma Surg. 2015, 135, 1511–1517. [Google Scholar] [CrossRef]
  12. Dai, Y.X.; Tai, Y.H.; Chen, C.C.; Chang, Y.T.; Chen, T.J.; Chen, M.H. Bidirectional association between alopecia areata and major depressive disorder among probands and unaffected siblings: A nationwide population-based study. J. Am. Acad. Dermatol. 2020, 82, 1131–1137. [Google Scholar] [CrossRef] [PubMed]
  13. Dai, Y.X.; Chen, C.C.; Tai, Y.H.; Chang, Y.T.; Chen, T.J.; Chen, M.H. Increased risk of major depressive disorder among probands with psoriasis and unaffected siblings: A nationwide population-based study. J. Eur. Acad. Dermatol. Venereol. 2020, 34, 1510–1515. [Google Scholar] [CrossRef] [PubMed]
  14. Dai, Y.X.; Yeh, F.Y.; Shen, Y.J.; Tai, Y.H.; Chou, Y.J.; Chang, Y.T.; Chen, T.J.; Li, C.P.; Wu, C.Y. Cigarette smoking, alcohol consumption, and risk of alopecia areata: A population-based cohort study in Taiwan. Am. J. Clin. Dermatol 2020. (Epub ahead of print). [Google Scholar] [CrossRef] [PubMed]
  15. Tai, Y.H.; Chen, T.L.; Cherng, Y.G.; Yeh, C.C.; Chang, C.C.; Liao, C.C. Previous use of mammography as a proxy for general health checks in association with better outcomes after major surgeries. Int. J. Environ. Res. Public Health 2019, 16, 4432. [Google Scholar] [CrossRef] [Green Version]
  16. Tai, Y.H.; Chang, C.C.; Yeh, C.C.; Sung, L.C.; Hu, C.J.; Cherng, Y.G.; Chen, T.L.; Liao, C.C. Long-term risk of stroke and poststroke outcomes in patients with heart failure: Two nationwide studies. Clin. Epidemiol. 2020, 12, 1235–1244. [Google Scholar] [CrossRef]
  17. Zhang, B.; Wang, H.E.; Bai, Y.M.; Tsai, S.J.; Su, T.P.; Chen, T.J.; Wang, Y.P.; Chen, M.H. Inflammatory bowel disease is associated with higher dementia risk: A nationwide longitudinal study. Gut 2020. (Epub ahead of print). [Google Scholar] [CrossRef]
  18. National Health Insurance Research Database. Data Subsets. Available online: https://nhird.nhri.org.tw/en/Data_Subsets.html (accessed on 11 November 2020).
  19. Arvanitakis, Z.; Shah, R.C.; Bennett, D.A. Diagnosis and management of dementia: Review. JAMA 2019, 322, 1589–1599. [Google Scholar] [CrossRef]
  20. Khuri, S.F.; Daley, J.; Henderson, W.; Hur, K.; Demakis, J.; Aust, J.B.; Chong, V.; Fabri, P.J.; Gibbs, J.O.; Grover, F.; et al. The Department of Veterans Affairs’ NSQIP: The first national, validated, outcome-based, risk-adjusted, and peer-controlled program for the measurement and enhancement of the quality of surgical care. National VA Surgical Quality Improvement Program. Ann. Surg. 1998, 228, 491–507. [Google Scholar] [CrossRef]
  21. Su, V.Y.; Liu, C.J.; Wang, H.K.; Wu, L.A.; Chang, S.C.; Perng, D.W.; Su, W.J.; Chen, Y.M.; Lin, E.Y.; Chen, T.J.; et al. Sleep apnea and risk of pneumonia: A nationwide population-based study. CMAJ 2014, 186, 415–421. [Google Scholar] [CrossRef] [Green Version]
  22. Cheng, C.L.; Lee, C.H.; Chen, P.S.; Li, Y.H.; Lin, S.J.; Yang, Y.H. Validation of acute myocardial infarction cases in the national health insurance research database in Taiwan. J. Epidemiol. 2014, 24, 500–507. [Google Scholar] [CrossRef] [Green Version]
  23. Hsieh, C.Y.; Chen, C.H.; Li, C.Y.; Lai, M.L. Validating the diagnosis of acute ischemic stroke in a National Health Insurance claims database. J. Med. Assoc. 2015, 114, 254–259. [Google Scholar] [CrossRef] [PubMed]
  24. Tai, Y.H.; Wu, H.L.; Mandell, M.S.; Lin, S.P.; Tsou, M.Y.; Chang, K.Y. The association of non-small-cell lung cancer recurrence with allogenic blood transfusion following surgical resection: A propensity score analysis of 1,803 patients. Eur. J. Cancer 2020, 140, 45–54. [Google Scholar] [CrossRef] [PubMed]
  25. Tai, Y.H.; Wu, H.L.; Mandell, M.S.; Tsou, M.Y.; Chang, K.Y. The association of allogeneic blood transfusion and the recurrence of hepatic cancer after surgical resection. Anaesthesia 2020, 75, 464–471. [Google Scholar] [CrossRef] [PubMed]
  26. Wu, H.L.; Tai, Y.H.; Lin, S.P.; Chan, M.Y.; Chen, H.H.; Chang, K.Y. The impact of blood transfusion on recurrence and mortality following colorectal cancer resection: A propensity score analysis of 4030 patients. Sci. Rep. 2018, 8, 13345. [Google Scholar] [CrossRef] [Green Version]
  27. Austin, P.C. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivar. Behav. Res. 2011, 46, 399–424. [Google Scholar] [CrossRef] [Green Version]
  28. Austin, P.C. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat. Med. 2009, 28, 3083–3107. [Google Scholar] [CrossRef] [Green Version]
  29. Myles, P.S. More than just morbidity and mortality-quality of recovery and long-term functional recovery after surgery. Anaesthesia 2020, 75, e143–e150. [Google Scholar] [CrossRef]
  30. Sprung, J.; Roberts, R.O.; Weingarten, T.N.; Nunes Cavalcante, A.; Knopman, D.S.; Petersen, R.C.; Hanson, A.C.; Schroeder, D.R.; Warner, D.O. Postoperative delirium in elderly patients is associated with subsequent cognitive impairment. Br. J. Anaesth. 2017, 119, 316–323. [Google Scholar] [CrossRef]
  31. Amado, L.A.; Perrie, H.; Scribante, J.; Ben-Israel, K.A. Preoperative cognitive dysfunction in older elective noncardiac surgical patients in South Africa. Br. J. Anaesth. 2020, 125, 275–281. [Google Scholar] [CrossRef]
  32. Silbert, B.; Evered, L.; Scott, D.A.; McMahon, S.; Choong, P.; Ames, D.; Maruff, P.; Jamrozik, K. Preexisting cognitive impairment is associated with postoperative cognitive dysfunction after hip joint replacement surgery. Anesthesiology 2015, 122, 1224–1234. [Google Scholar] [CrossRef]
  33. Shi, Z.; Mei, X.; Li, C.; Chen, Y.; Zheng, H.; Wu, Y.; Zheng, H.; Liu, L.; Marcantonio, E.R.; Xie, Z.; et al. Postoperative delirium is associated with long-term decline in activities of daily living. Anesthesiology 2019, 131, 492–500. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  34. Ha, A.; Krasnow, R.E.; Mossanen, M.; Nagle, R.; Hshieh, T.T.; Rudolph, J.L.; Chang, S.L. A contemporary population-based analysis of the incidence, cost, and outcomes of postoperative delirium following major urologic cancer surgeries. Urol. Oncol. 2018, 36, 341.e15–341.e22. [Google Scholar] [CrossRef] [PubMed]
  35. Brown, C.H., IV; Laflam, A.; Max, L.; Lymar, D.; Neufeld, K.J.; Tian, J.; Shah, A.S.; Whitman, G.J.; Hogue, C.W. The impact of delirium after cardiac surgical procedures on postoperative resource use. Ann. Thorac. Surg. 2016, 101, 1663–1669. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  36. Weinstein, S.M.; Poultsides, L.; Baaklini, L.R.; Mörwald, E.E.; Cozowicz, C.; Saleh, J.N.; Arrington, M.B.; Poeran, J.; Zubizarreta, N.; Memtsoudis, S.G. Postoperative delirium in total knee and hip arthroplasty patients: A study of perioperative modifiable risk factors. Br. J. Anaesth. 2018, 120, 999–1008. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  37. Sieber, F.E.; Zakriya, K.J.; Gottschalk, A.; Blute, M.R.; Lee, H.B.; Rosenberg, P.B.; Mears, S.C. Sedation depth during spinal anesthesia and the development of postoperative delirium in elderly patients undergoing hip fracture repair. Mayo Clin. Proc. 2010, 85, 18–26. [Google Scholar] [CrossRef] [Green Version]
  38. Wildes, T.S.; Mickle, A.M.; Ben Abdallah, A.; Maybrier, H.R.; Oberhaus, J.; Budelier, T.P.; Kronzer, A.; McKinnon, S.L.; Park, D.; Torres, B.A.; et al. Effect of electroencephalography-guided anesthetic administration on postoperative delirium among older adults undergoing major surgery: The ENGAGES randomized clinical trial. JAMA 2019, 321, 473–483. [Google Scholar] [CrossRef] [Green Version]
  39. Patel, V.; Champaneria, R.; Dretzke, J.; Yeung, J. Effect of regional versus general anaesthesia on postoperative delirium in elderly patients undergoing surgery for hip fracture: A systematic review. BMJ. Open 2018, 8, e020757. [Google Scholar] [CrossRef]
  40. Djaiani, G.; Silverton, N.; Fedorko, L.; Carroll, J.; Styra, R.; Rao, V.; Katznelson, R. Dexmedetomidine versus propofol sedation reduces delirium after cardiac surgery: A randomized controlled trial. Anesthesiology 2016, 124, 362–368. [Google Scholar] [CrossRef]
  41. Heneka, M.T.; Golenbock, D.T.; Latz, E. Innate immunity in Alzheimer’s disease. Nat. Immunol. 2015, 16, 229–236. [Google Scholar] [CrossRef]
  42. Bettcher, B.M.; Johnson, S.C.; Fitch, R.; Casaletto, K.B.; Heffernan, K.S.; Asthana, S.; Zetterberg, H.; Blennow, K.; Carlsson, C.M.; Neuhaus, J.; et al. Cerebrospinal fluid and plasma levels of inflammation differentially relate to CNS markers of Alzheimer’s disease pathology and neuronal damage. J. Alzheimer’s Dis 2018, 62, 385–397. [Google Scholar] [CrossRef]
  43. Degerskär, A.N.W.; Englund, E.M. Cause of death in autopsy-confirmed dementia disorders. Eur. J. Neurol. 2020. (Epub ahead of print). [Google Scholar] [CrossRef] [PubMed]
  44. Faux, N.G.; Rembach, A.; Wiley, J.; Ellis, K.A.; Ames, D.; Fowler, C.J.; Martins, R.N.; Pertile, K.K.; Rumble, R.L.; Trounson, B.; et al. An anemia of Alzheimer’s disease. Mol. Psychiatry 2014, 19, 1227–1234. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  45. Wolters, F.J.; Zonneveld, H.I.; Licher, S.; Cremers, L.; Ikram, M.K.; Koudstaal, P.J.; Vernooij, M.W.; Ikram, M.A. Hemoglobin and anemia in relation to dementia risk and accompanying changes on brain MRI. Neurology 2019, 93, e917–e926. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  46. Lutsey, P.L.; Chen, N.; Mirabelli, M.C.; Lakshminarayan, K.; Knopman, D.S.; Vossel, K.A.; Gottesman, R.F.; Mosley, T.H.; Alonso, A. Impaired Lung Function, Lung Disease, and Risk of Incident Dementia. Am. J. Respir. Crit. Care Med. 2019, 199, 1385–1396. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  47. Gill, D.P.; Hubbard, R.A.; Koepsell, T.D.; Borrie, M.J.; Petrella, R.J.; Knopman, D.S.; Kukull, W.A. Differences in rate of functional decline across three dementia types. Alzheimer’s Dement 2013, 9, S63–S71. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  48. Manabe, T.; Mizukami, K.; Akatsu, H.; Hashizume, Y.; Ohkubo, T.; Kudo, K.; Hizawa, N. Factors associated with pneumonia-caused death in older adults with autopsy-confirmed dementia. Intern. Med. 2017, 56, 907–914. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  49. Jørgensen, I.F.; Aguayo-Orozco, A.; Lademann, M.; Brunak, S. Age-stratified longitudinal study of Alzheimer’s and vascular dementia patients. Alzheimer’s Dement 2020, 16, 908–917. [Google Scholar] [CrossRef]
  50. Ravona-Springer, R.; Davidson, M.; Noy, S. Is the distinction between Alzheimer’s disease and vascular dementia possible and relevant? Dialogues Clin. Neurosci. 2003, 5, 7–15. [Google Scholar]
  51. Xie, J.; Brayne, C.; Matthews, F.E.; Medical Research Council Cognitive Function and Ageing Study Collaborators. Survival times in people with dementia: Analysis from population based cohort study with 14 year follow-up. BMJ 2008, 336, 258–262. [Google Scholar] [CrossRef] [Green Version]
  52. Sanders, C.L.; Wengreen, H.J.; Schwartz, S.; Behrens, S.J.; Corcoran, C.; Lyketsos, C.G.; Tschanz, J.T.; Cache County Investigators. Nutritional status is associated with severe dementia and mortality: The Cache County Dementia Progression Study. Alzheimer’s Dis. Assoc. Disord 2018, 32, 298–304. [Google Scholar] [CrossRef]
Ijerph 17 08431 g001 550
Figure 1. Flow diagram for patient selection.
Figure 1. Flow diagram for patient selection.
Ijerph 17 08431 g001
Table
Table 1. Baseline characteristics of dementia cases and matched controls.
Table 1. Baseline characteristics of dementia cases and matched controls.
Baseline CharacteristicDementia
n = 7863		Control
n = 7863		Standardized Difference †
Age (years), mean (SD)77.010.077.410.0−0.0400
Sex, n (%) 0.0141
Male374147.6369146.9
Female412252.4417253.1
Monthly premium (USD), n (%) 0.0143
0–500568472.3569872.5
501–800200225.5203025.8
≥8011772.31351.7
Medication for dementia, n (%)
Donepezil3754.800.0NA
Galantamine560.700.0NA
Rivastigmine2763.500.0NA
Memantine520.700.0NA
Comorbidity, n (%)
Hypertension534968.0538868.5−0.0126
Diabetes270234.4273234.7−0.0093
Ischemic heart disease232029.5229329.20.0091
Atherosclerosis2493.22623.3−0.0290
Cardiac dysrhythmias121015.4120215.30.0043
Heart failure105913.5104113.20.0109
Liver cirrhosis1962.51922.40.0117
COPD198825.3192124.40.0252
Chronic kidney disease7109.06478.20.0561
Cerebrovascular disease346644.1348944.4−0.0065
Parkinson’s disease91011.67149.10.1491
Malignancy91411.687611.10.0264
Sarcopenia740.9730.90.0076
Obesity240.3210.30.0738
Type of anesthesia, n (%) 0.0098
General anesthesia428954.5429854.7
Regional anesthesia232029.5235930.0
Other125416.0120615.3
Type of surgery, n (%) 0.0132
Orthopedic284536.2287536.6
Cardiovascular89211.386411.0
Neurosurgery90811.593511.9
Gastrointestinal6518.36618.4
Hepato-biliary-pancreatic3764.83654.6
Genitourinary84810.886711.0
ENT2873.72873.7
Gynecology 1471.91451.8
Breast570.7530.7
Other85210.981110.4
Number of hospitalizations, n (%) 0.1142
0395350.3436455.5
1183223.3175522.3
≥2207826.5174422.2
Number of ER visits, n (%) 0.1311
0270634.4312539.7
1197725.1202725.8
≥2318040.5271134.5
Abbreviation: COPD, chronic obstruction pulmonary disease; ENT, ear, nose, and throat; ER, emergency room; SD, standard deviation; USD, United States Dollar. † Standardized difference of ≥0.2 indicates a significant imbalance in a variable between exposure groups.
Table
Table 2. Postoperative mortality and complications for dementia patients and controls.
Table 2. Postoperative mortality and complications for dementia patients and controls.
Outcome of InterestDementiaControlPerioperative Riskp
EventRate (%)EventRate (%)aOR (95% CI) †
30-day in-hospital mortality520.7300.41.71 (1.09–2.70)0.0209
180-day in-hospital mortality2783.51882.41.49 (1.23–1.81)<0.0001
365-day in-hospital mortality4265.42873.71.52 (1.30–1.78)<0.0001
Major complications
Pneumonia1702.21151.51.48 (1.16–1.88)0.0015
Urinary tract infection2423.11582.01.59 (1.30–1.96)<0.0001
Pyelonephritis160.280.12.09 (0.89–4.91)0.0892
Surgical site infection380.5300.41.27 (0.79–2.07)0.3272
Sepsis1381.8791.01.77 (1.34–2.34)<0.0001
Acute myocardial infarction150.2120.21.27 (0.59–2.75)0.5383
Stroke640.8610.81.07 (0.75–1.53)0.6949
Pulmonary embolism70.100.0>999.99 (<0.01–>999.99)0.8834
Deep vein thrombosis40.150.10.86 (0.23–3.32)0.8321
Cardiac dysrhythmias580.7460.61.34 (0.90–1.98)0.1514
Acute renal failure520.7380.51.36 (0.89–2.08)0.1535
Postoperative bleeding60.170.10.80 (0.26–2.42)0.6878
Blood transfusion2993.82292.91.32 (1.11–1.58)0.0022
Admission to ICU1852.41341.71.40 (1.12–1.76)0.0036
Abbreviation: aOR, adjusted odds ratio; CI, confidence interval; ICU, intensive care unit. † Adjusted for all covariates listed in Table 1.
Table
Table 3. Sensitivity analyses for 30-day in-hospital mortality in patients with dementia compared with controls.
Table 3. Sensitivity analyses for 30-day in-hospital mortality in patients with dementia compared with controls.
Statistical Model30-Day in-Hospital Mortality
cOR (95% CI)paOR (95% CI) †p
Primary model1.74 (1.11–2.73)0.01611.71 (1.09–2.70)0.0209
Model 1 a1.72 (1.07–2.77)0.02651.78 (1.10–2.90)0.0200
Model 2 b1.93 (1.16–3.19)0.01101.95 (1.17–3.27)0.0108
Model 3 c1.94 (1.19–3.15)0.00751.96 (1.20–3.21)0.0074
Abbreviation: cOR, crude odds ratio; aOR, adjusted odds ratio; CI, confidence interval. a Model 1: excluding patients with dementia diagnosis <1 year before surgery. b Model 2: excluding patients undergoing cardiovascular surgery. c Model 3: excluding patients diagnosed with any type of cancer before surgery. † Adjusted for all covariates listed in Table 1.
Table
Table 4. Subgroup analysis for postoperative mortality and complications associated with dementia.
Table 4. Subgroup analysis for postoperative mortality and complications associated with dementia.
SubgroupDementia/
Control		nPerioperative Risk †
EventRate (%)aOR (95% CI) ‡p
Age ≥ 65 yearsDementia706487212.31.26 (1.13–1.40)<0.0001
Control71187079.9Reference
Age < 65 yearsDementia799658.10.99 (0.67–1.46)0.9594
Control745658.7Reference
MaleDementia374147912.81.14 (0.99–1.32)0.0679
Control369142011.4Reference
FemaleDementia412245811.11.35 (1.16–1.56)<0.0001
Control41723528.4Reference
Senile dementiaDementia580571812.41.27 (1.14–1.42)<0.0001
Control78637729.8Reference
Vascular dementiaDementia8869010.20.96 (0.76–1.21)0.7189
Control78637729.8Reference
Alzheimer’s dementiaDementia4165312.71.45 (1.07–1.96)0.0167
Control78637729.8Reference
Dementia medicationDementia696598.50.92 (0.70–1.22)0.5769
Control78637729.8Reference
No dementia medicationDementia716787812.21.27 (1.14–1.41)<0.0001
Control78637729.8Reference
Dementia diagnosis ≥ 5 yearsDementia17561739.91.03 (0.86–1.23)0.7390
Control78637729.8Reference
Dementia diagnosis < 5 yearsDementia610776412.51.30 (1.17–1.45)<0.0001
Control78637729.8Reference
General anesthesiaDementia428948211.21.28 (1.11–1.47)0.0009
Control42983848.9Reference
Regional anesthesiaDementia232026711.51.32 (1.09–1.60)0.0052
Control23592159.1Reference
Abbreviation: aOR, adjusted odds ratio; CI, confidence interval. † Includes 30-day in-hospital mortality, pneumonia, urinary tract infection, pyelonephritis, surgical site infection, sepsis, acute myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis, cardiac dysrhythmias, acute renal failure, postoperative bleeding, blood transfusion, and admission to ICU. ‡ Adjusted for all the covariates listed in Table 1.
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Wu, Y.-M.; Kuo, H.-C.; Li, C.-C.; Wu, H.-L.; Chen, J.-T.; Cherng, Y.-G.; Chen, T.-J.; Dai, Y.-X.; Liu, H.-Y.; Tai, Y.-H. Preexisting Dementia Is Associated with Increased Risks of Mortality and Morbidity Following Major Surgery: A Nationwide Propensity Score Matching Study. Int. J. Environ. Res. Public Health 2020, 17, 8431. https://doi.org/10.3390/ijerph17228431

AMA Style

Wu Y-M, Kuo H-C, Li C-C, Wu H-L, Chen J-T, Cherng Y-G, Chen T-J, Dai Y-X, Liu H-Y, Tai Y-H. Preexisting Dementia Is Associated with Increased Risks of Mortality and Morbidity Following Major Surgery: A Nationwide Propensity Score Matching Study. International Journal of Environmental Research and Public Health. 2020; 17(22):8431. https://doi.org/10.3390/ijerph17228431

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Wu, Yu-Ming, Hsien-Cheng Kuo, Chun-Cheng Li, Hsiang-Ling Wu, Jui-Tai Chen, Yih-Giun Cherng, Tzeng-Ji Chen, Ying-Xiu Dai, Hsin-Yi Liu, and Ying-Hsuan Tai. 2020. "Preexisting Dementia Is Associated with Increased Risks of Mortality and Morbidity Following Major Surgery: A Nationwide Propensity Score Matching Study" International Journal of Environmental Research and Public Health 17, no. 22: 8431. https://doi.org/10.3390/ijerph17228431

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