Association between serum lipoprotein levels and cognitive impairment in acute cerebral infarction

Abstract Background: The objective of this study is to examine the association between serum lipoprotein levels (SLL) and cognitive impairment (CI) in patients with acute cerebral infarction (ACI). Methods: All published studies will be searched from the following electronic databases: PubMed, EMBASE, Cochrane Library, PsycINFO, Web of Science, WANGFANG, and China National Knowledge Infrastructure from inauguration of each electronic database up to March 1, 2020. In addition, we will also search other sources, such as dissertations, Google scholar, conference proceedings, and reference lists of relevant reviews. We will not apply any language restrictions to the electronic databases. Two researchers will independently carry out literature selection, data collection, and methodological quality. A third researcher will help to solve any divergences by discussion. The RevMan 5.3 software will be employed to pool the collected data and to analyze the outcome data. Results: This study will scrutinize the association between SLL and CI in patients with ACI. Conclusions: The results of this study will present helpful evidence of the association between SLL and CI in patients with ACI. Registration number: INPLASY202040018.


Introduction
Acute cerebral infarction (ACI) is a very common type of stroke, which accounts for about 70% of all stroke patients. [1][2][3][4] It is estimated that ACI may result in 6.2 million deaths around the world each year, [5,6] Patients with such disorder often accompanies a variety of complications, such as paralysis or loss of muscle movement, difficulty talking or swallowing, memory loss or thinking difficulties, pain, emotional problems, and cognitive impairment (CI). [7][8][9][10][11] Of those, CI often greatly affects quality of life in ACI patients. [12,13] Serum lipoprotein has a certain predictive effect on the longterm clinical prognosis of patients with ACI. [14] It pays a very important role in acute cerebral protection and cerebral vascular recovery. [15] Studies have found that CI is associated with serum lipoprotein levels (SLL) in ACI patients. [16][17][18][19][20][21] Previous studies have investigated the association between SLL and CI in patients with ACI. However, no systematic review has been conducted to explore this topic. Therefore, this study will systematically investigate the association between SLL and CI in patients with ACI.

Study registration
We have registered this study on INPLASY202040018. It has been organized based on the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Protocol statement. [22] 3. Criteria for including studies

Types of studies
We will include case-controlled studies that examined the association between SLL and CI in patients with ACI. However, we will exclude animal studies, case report, case series, and uncontrolled clinical studies.  The authors have no conflicts of interest to disclose.
Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

Types of exposures
In the experimental group, all participants experienced ACI.
In the control group, all participants were healthy without ACI.

Types of patients
We will include subjects who had diagnosed as ACI, or who were healthy participants, regardless their race, sex, and age.

Types of outcome measurements
Outcomes are SLL and CI. SLL is examined by enzyme linked immunosorbent assay. CI is measured by any relevant scales, such as Montreal Cognitive Assessment Scale, mini-mental state examination scale, or related tools.

Data sources and search
The comprehensive search strategy will be carried out in the following electronic databases from their inauguration up to March 1, 2020: PubMed, EMBASE, Cochrane Library, Psy-cINFO, Web of Science, WANGFANG, and China National Knowledge Infrastructure. We will not apply language and publication time limitations to any literature searches. The sample of search strategy for PubMed is created in Table 1. We will also adapt similar search strategies for other electronic databases.
To avoid missing potential studies, we will also check other literature resources, such as Google Scholar, dissertations, conference abstracts, and reference lists of related reviews.

Study selection
All retrieved citations will be exported into EndNote X7 software and duplicated records will be excluded. Titles and abstracts will be identified by 2 independent investigators, and all unrelated citations will be eliminated. After that, potential articles in fulltext will be cautiously examined against all inclusion criteria. Reasons for all exclusions will be recorded and reported. Any disagreements that arise at each stage between two investigators will be solved through consensus with the help of another experienced investigator. We will demonstrate the process of study selection in a PRISMA flow diagram.

Data extraction
Data will be extracted from each eligible study by 2 independent investigators using an advance-designed data extraction sheet. Any differences between two investigators will be resolved by another experienced investigator through discussion. The extracted data includes study information (first author, time of publication, et al), participant characteristics (gender, age, sample size, severity and duration of ACI, et al), study methods, exposures, outcomes, results, findings, and follow-up information. If we identify any missing or insufficient data, we will contact original authors to request it.

Study quality assessment
Two investigators will independently appraise methodological quality for each included study using Newcastle-Ottawa Scale. [23] Any uncertainty between 2 investigators will be solved by another experienced investigator through discussion, and a final decision will be made.

Subgroup analysis
We will conduct subgroup analysis to identify any possible sources of heterogeneity and inconsistency according to the different characteristics of study and patient, and outcomes.

Sensitivity analysis
We will examine sensitivity analysis to test the robustness of conclusions by removing low quality studies.

Reporting bias
We will conduct a funnel plot and Egger regression test to explore any possible reporting bias if over 10 studies are included. [24,25] 6. Data synthesis RevMan 5.3 software will be used to pool and to analyze all data in this study. We will express continuous data as weighted mean difference or standardized mean difference and 95% confidence intervals, and dichotomous data as risk ratio and 95% confidence intervals. We will test statistical heterogeneity by I 2 statistics. I 2 50% indicates acceptable heterogeneity, and a fixed-effect model will be used, while I 2 > 50% suggests substantial heterogeneity, and a random-effect model will be employed. If I 2 50% is identified among sufficient eligible case-controlled studies, we Table 1 Search strategy for PubMed.

Number
Search Terms will perform a meta-analysis. On the other hand, if I 2 > 50% is examined, we will carry out a subgroup analysis and sensitivity analysis to explore the sources of heterogeneity.

Discussion
Several clinical studies have investigated the association between SLL and CI in patients with ACI. So far, no study has been performed to explore the association between SLL and CI in ACI. Therefore, this study will firstly investigate the association between SLL and CI in ACI. This study aims to summarize the most recent evidence of the association between SLL and CI in ACI. The results of this study may provide evidence for clinical practice.

Ethics and dissemination
This study will not require any ethical approval documents, since it will not collect privacy data. We plan to publish this study on a peer-reviewed journal.