Association between dementia and mortality in the elderly patients undergoing hip fracture surgery: a meta-analysis

Objective This study was designed to verify the association between dementia and mortality in the elderly undergoing hip fracture surgery, and assessed the mortality of patients with dementia after hip fracture surgery. Material and methods PubMed, Embase, and Web of Science were searched until April, 2018 without language restrictions. Two reviewers selected related studies, assessed study quality, and extracted data independently. Risk ratios (RRs) with 95% confidence intervals (CI) were derived using random-effects model throughout all analyses. The endpoints included 30-day, 6-month, 1-year, and more than 1-year mortality. This meta-analysis was performed following PRISMA statement and carried out by using stata14.0 software. Results Dementia significantly increased postoperative mortality of patients suffered from hip fracture in 30-day [RR = 1.57, 95% CI (1.29, 1.90), P<0.00], 6-month [RR = 1.97, 95% CI (1.47, 2.63), P<0.00], 1-year [RR = 1.77, 95% CI (1.54, 2.04), P<0.00], and more than 1-year follow up [RR = 1.60, 95% CI (1.30, 1.96), P<0.00] respectively. The mortality of dementia patients after hip fracture surgery in 30-day [ES = 12%, 95% CI (8%, 15%)], 6-month [ES = 32%, 95% CI (17%, 48%)], 1-year [ES = 39%, 95% CI (35%, 43%)], and more than 1-year follow up [ES = 45%, 95% CI (32%, 58%)]. Conclusions Our meta-analysis demonstrated that the mortality of patients with dementia suffered from hip fracture surgery is 12%, 32%, 39%, and 45%, and dementia increased 1.57, 1.97, 1.77, and 1.60-fold mortality in patients undergoing hip fracture surgery in 30-day, 6-month, 1-year, and more than 1-year follow up respectively.


Introduction
Hip fractures are being paid more attention due to higher morbidity and mortality. These patients usually have poor body compensatory capacity and comorbidities, such as dementia. Dementia is a syndrome characterized by persistent impairment in cognitive function or behavioral abnormalities. Due to the progress of aging society, dementia prevalence increases exponentially with age, it is estimated that the number of patients with dementia may reach 65.7 million in 2030 and 115.4 million in 2050 [1].
Dementia is not as fatal as deep vein thrombosis or pulmonary embolism in the short term, so it did not cause clinicians to pay enough attention, and it is unclear that the mortality of patients with dementia suffered from hip fracture surgery. Therefore, we performed a meta-analysis based on plenty of previous achievements in current research, to identify the effects of dementia on postoperative mortality of hip fracture, and the incidence of death in patients with dementia undergoing hip fracture surgery in 30 days, 6 months, 1 year, and more than 1 year follow up, and provided more convincing evidences for clinicians.

Materials and methods
We carried out this meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement [2] and Cochrane Collaboration guidelines strictly [3].

Search strategy
We searched PubMed, Embase, and Web of Science until April, 2018, without language restrictions. In addition, the references of the included studies were manual searched to identify any additional articles. The following keywords were adopted in the database search: "hip fracture," "mortality," and "dementia." The Boolean operators were used to combine them.

Study selection and eligibility criteria
The inclusion criteria are as follows: (1) studies examined the relationship between dementia and mortality among elderly patients undergoing hip fracture surgery; (2) the sample size was more than 200; (3) study designs were cohort study; (4) the mean age is greater than 60 years. The exclusion criteria are as follows: (1) other types of fractures included; (2) studies provided insufficient data; (3) case report, review, commentary, and study just included an abstract; (4) dementia with other psychiatric disorders.

Data extraction
Two reviewers (JZ B and P Z) independently extracted the following information from each study: first author, year of publication, country, study design, sample size, mean age, diagnostic criteria for dementia, and duration of follow-up (in-hospital, perioperative setting, 30-day, 6-month, 1-year and more than 1-year). Any discrepancies were resolved following discussion. All extracted data were entered into a predefined standardized Excel (Microsoft Corporation, USA) file carefully.

Quality assessment
We evaluated the quality of studies by Newcastle-Ottawa Scale (NOS), which is a risk of bias assessment tool for observational studies [4]. This scale contains a number of answers per question ranging from two to five. Highquality responses earn a star, totaling up to nine stars. We set scores of 0-3, 4-6, and 7-9 for low, moderate, and high quality of studies, respectively [5].

Statistical analysis
Statistical analyses were performed by using STATA 14.0 (StataCorp LP). The association between dementia and mortality was described as risk ratios (RR) with 95% confidence intervals (CI) by using random models. P ≤ 0.05 was regarded as statistically significant. Statistical heterogeneity was assessed by the Cochran Q test and quantified by the I 2 statistic [6], and an I 2 value greater than 50% indicates significant heterogeneity. When significant heterogeneity existed, heterogeneity analysis would be conducted to make a further explanation. We divided the follow-up time into four timepoints: 30-day, 6-month, 1-year, and more than 1-year follow-up. We classified the in-hospital and perioperative mortality as 30-day mortality.

Main findings
Our meta-analysis demonstrated that the mortality of patients with dementia suffered from hip fracture surgery is 12%, 32%, 39%, and 45%, and dementia increased 1.57, 1.97, 1.77, and 1.60-fold mortality in patients undergoing hip fracture surgery in 30-day, 6-month, 1-year, and more than 1-year follow-up. A previous meta-analysis included 75 studies, and involving 64,316 patients [25], the pooled outcomes demonstrated that the overall inpatient or 1 month mortality was 13.3%, 3 to 6 months was 15.8%, 1 year 24.5%, and 2 years 34.5% in generally patients, which mortality was significantly lower than patients with dementia who underwent hip fracture surgery.

Comparison with other studies
To the best of our knowledge, there are three meta-analyses that described risk factors for postoperative mortality after hip fracture surgery [25][26][27], which dementia is one of these risk factors. However, these meta-analyses included fewer literatures for the indicator of dementia, and inconsistent follow-up time made conclusions less convincing. Therefore, we performed an update meta-analysis to evaluate the effects of dementia on postoperative mortality of patients undergoing hip fracture surgery and the incidence of death in patients with dementia undergoing hip fracture surgery in 30 days, 6 months, 1 year, and more than 1 year follow-up.

Implications for clinical practice
Dementia has not received enough attention compared with deep vein thrombosis and pulmonary embolism in patients with hip fracture. However, our pooled results demonstrated that more than one third of people with dementia will die after hip fracture surgery in a 1-year follow-up and about one in two in more than 1-year follow-up. Patients with dementia usually have less activity and poor self-care ability, which increased postoperative complications, such as surgical site infection, urinary tract infection, and respiratory complications [28]. Therefore, orthopedists should attach great importance to this age-related disease, instead of just focusing    on hip fracture problems. Besides, they should fully assess whether the dementia patients are suitable for surgical treatment after suffering from a hip fracture. Can surgical treatment improve the quality of life and prolong life span of patients, especially for patients with severe dementia? For patients with dementia who underwent hip fracture surgery, we should establish a multidisciplinary model of diagnosis and treatment to improve the postoperative outcomes [29]. Besides, nursing cares are necessary to prevent the adverse outcomes of dementia postoperatively [30], such as aspiration, pressure sore, deep vein thrombosis, and pneumonia. Further, rehabilitate exercises are needed to restore function as much as possible after discharge.

Call for future studies
Our results show that patients with dementia have very high mortality rates after undergoing hip fracture surgery. Mortality will be higher for patients with severe dementia. It is unclear whether surgical treatment could improve quality of life and prolong life-span of patients with severe dementia. Until recently, there is no relevant meta-analysis or clinical guidelines to elaborate on this issue. We recommend that future studies should focus on which one is better for the treatment of patients with severe dementia who suffered from hip fracture, surgery, or conservative treatment. Besides, clinical decision makers should formulate relevant clinical guidelines to guide clinicians in the treatment of patients with dementia suffered from hip fracture.

Heterogeneity analysis
The pooled results indicated that significant heterogeneity was found in some indicators. For the prevalence of death of patients with dementia after hip fracture surgery, (1) we conducted a sensitivity analysis through the deletion of Jantzen et al's study [13], and the heterogeneity was reduced from 77.5 to 0.0% in 30-day mortality; (2) we excluded each study of the outcomes one at a time in 1-year mortality, but the heterogeneity was still very high. Unequal levels of regional medical care and significant sample size difference in the included studies may be the major sources of heterogeneity. For the effect of dementia on postoperative mortality, there was significant heterogeneity in 1-year mortality. The heterogeneity was reduced from 91.7 to 33.8% after the removal of Mitchell et al's study [22]. Only two studies were included in 6-month mortality, which may be the main source of heterogeneity. In terms of more than 1-year mortality, the inconsistency of follow-up time and obvious sample size differences, which may be major sources of higher heterogeneity.

Strengths and limitations of this meta-analysis
The major strengths of this study were the following: (1) our study was restricted to the elderly dementia patients undergoing hip fracture surgery, which were higher homogeneous and selective; (2) we designed our meta-analysis into four timepoints: 30-day, 6-month, 1-year, and more than 1-year follow up, and follow-up time is consistent; (3) we calculated the mortality of patients with dementia suffered from hip fracture surgery.
Limitations of this meta-analysis must be considered. First, although the patients we included in the study were elderly patients, it is difficult to make the confounding variables among the studies exactly the same. Second, we did not classify dementia into mild, moderate, and severe dementia because no related data were available in the original studies. Third, there was a great difference in the sample size of the included studies, which may affect the accuracy of our results to some extent. Fourth, significant heterogeneity was found in some outcomes. Last, although we conducted a comprehensive search of literature, it was hard to rule out the existence of publication bias.

Conclusions
Our meta-analysis demonstrated that the mortality of people with dementia suffered from hip fracture surgery is 12%, 32%, 39%, and 45%, and dementia increased 1.57-, 1.97-, 1.77-, and 1.60-fold mortality in patients undergoing hip fracture surgery in 30-day, 6-month, 1-year, and more than 1-year follow-up. Future large-volume, well-designed studies, and the outcomes of multivariable analysis with extensive follow-up are awaited to confirm and update the findings of our analysis.