Potential patients were prospectively recruited from two centers in Chongqing, a municipality in southwest China, from September 2018 to August 2019. Ethical approval was obtained from the Ethics Committee of the Second Affiliated Hospital, Chongqing Medical University before recruitment (Reference number: 2018-252). All participants provided their written informed consent before participation.
Inclusion and exclusion criteria
The participants who met all of the following inclusion criteria were included: (1) patients diagnosed with unilateral hemispheric subacute stroke (i.e. more than one month after stroke onset) using neuroimaging evidence from either computer tomography (CT) or magnetic resonance imaging (MRI); (2) patients that were aged between 18 to 80 years; (3) Chinese (Mandarin)-speakers; and (4) patients who are able to communicate and to follow at least one-step commands.
The participants who met any of the following criteria were excluded: (1) patients with severe aphasia, swallowing disorders or other complications post-stroke that prevent them from successfully completing the assessments; (2) patients with any previously known psychiatric disorder or neurological disease excluding stroke; (3) patients who have been assessed by the MoCA or NCSE within the past three months and (4) those who refuse to participate in this study.
Cognitively normal healthy controls were enrolled from the relatives of the patients or staff in the hospital, with an inclusion criterion of: (1) no known history of neurological or psychiatric disorders; (2) no complaints of prior cognitive issues; (3) Chinese (Mandarin)-users and (4) agreement to participate in this study.
Materials and Procedures
Montreal Cognitive Assessment (MoCA)
The MoCA Chinese (Mandarin) version-1 (from http://www.mocatest.org) was used in this study. The total score for the MoCA is 30 and it covers seven domains of cognition: visuospatial/executive functions (trail-making test: 1 point, copy tube: 1 point and clock drawing task: 3 points), naming (3 points), attention (forward digit span: 1 point, backward digit span: 1 point, vigilance: 1 point and serial 7 subtraction: 3 points), language (sentence repetition: 2 points, verbal fluency: 1 point), abstraction (2 points), delayed recall (5 points) and orientation (6 points) [1]. According to previous studies on the MoCA based on the Chinese population, we added one point to the final scores of the MoCA if the participants had 6 years of formal school-based education or fewer [15].
National Institute for Neurological Disorders and Stroke-Canadian Stroke Network 5-Minute protocol (NINDS-CSN 5-min Protocol)
The NINDS-CSN 5-min protocol was performed by extracting three items (i.e. orientation, delayed recall and verbal fluency) from the full MoCA, which results in a total score of 12 [5, 6].
Montreal Cognitive Assessment 5-minute Protocol (MoCA 5-min protocol)
The MoCA 5-min protocol was previously developed by Wong et al. [7]. The protocol first starts with an attention task by using the first trial of the 5-word delayed recall test. Second, verbal fluency score was evaluated based on the output of the effective number of words, rather than using a single cut-off value based on the number of animal names. Third, the recall test was conducted with cues (category and multiple-choice) to understand the type of memory failure, in addition to general evaluation of spontaneous recall. The total score of MoCA 5-minute protocol was thus set at 30.
The Chinese (Mandarin) version of the MoCA 5-min protocol was based on the Hong Kong version of the MoCA 5-min protocol and the MoCA Chinese (Mandarin) version-1. We requested permission for research use of the assessments through the MoCA test copyright owner Dr. Ziad Nasreddine via http://mocatest.org.
Neurobehavioral Cognitive Status Examination (NCSE)
The Chinese (Mandarin) version of NCSE was used in this study [14]. This examination covers 10 sections: orientations, attention, comprehension, repetition, naming, construction, memory, calculation, similarities and judgement. All sections, except orientation and memory, contain 1 screening task and series of metric tests with a gradual increase in difficulty. The total score of the NCSE is 82. In line with prior studies, a cut-off value of 65 was used to define the cut-off for cognitive impairment in patients with stroke [16].
Statistical Analysis
SPSS version 23.0 and MedCalc version 15.6 were used for statistical analysis. Scatter plots were drawn before performing correlation analyses. Independent t-tests were used to compare the baseline characteristics between patients with stroke and healthy controls. Receiver operating characteristics (ROC) curves were used to examine the ability of different assessments (the MoCA, the MoCA 5-min protocol and the NINDS-CSN 5-min protocol) to differentiate cognitive impairment identified by the NCSE (NCSE < 65 out of 82) and to differentiate patients with stroke from healthy controls. The area under the receiver operating characteristic curve (AUC) was calculated for each ROC curve to describe the general diagnostic accuracy of different assessments. The optimal cut-off value was derived for each point, whereupon both sensitivity and specificity were optimized using the maximized Youden Index. The Youden Index was calculated by the equation: sensitivity + specificity – 1 [17]. A non-parametric approach proposed by DeLong et al. was used to compare different ROCs [18]. Correlations among the assessments were tested by the Pearson’s correlation analysis test. Subsequent Pearson’s correlation tests were performed to explore the relationship between each item and total scores of the MoCA 5-min protocol and the NINDS-CSN 5-min protocol, with the aim to explore the individual contribution of each item. The statistically significant level was set at p < 0.05.