This study was a single-blinded randomized controlled trial for post-stroke patients with cognitive impairment. The protocol of this trial had been approved by the Ethics Committee of the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine (Approved number: 2017YJS-004-01) in 2017. This study was performed in accordance with the guidelines of Declaration of Helsinki and the informed consent was obtained from all participants and/or their legal guardians before screening. The details of this trial were also registered in China Clinical Trial Registry (Registration number: ChiCTR-INR-17013042; Registration date: 19/10/2017).
Eligible participants were recruited in the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine. All participants included should meet the following inclusion criteria: (1) meet diagnostic criteria for stroke according to the principles of 2010 Chinese guidelines for the management of hypertension 22 and confirmed by computed tomography or magnetic resonance imaging; (2) first-ever stroke and within one year post-stroke; (3) aged between 45 and 80 years old; (4) education level was primary school or above; (5) cognitive impairment was identified by the Fuzhou version of the Montreal cognitive assessment 23 with the scores between 10 and 26 points; (6) cognitive impairment occurred after stroke and excluded other causes; (7) participants included should be conscious and stable in vital signs; (8) participants could understand the operation of computer-aided training; (9) the participants themselves or their legal guardian had informed consent.
Exclusion criteria: (1) had severe visual or hearing impairment, mental disorders for their potential impacts on cognitive examination; (2) history of mental retardation and dementia before the occurrence of stroke; (3) had severe unilateral spatial neglect; (4) had depressive symptom (Hamilton Depression Scale score>7) 24; (5) had severe heart disease, liver failure, renal failure, malignant tumor, gastrointestinal bleeding or other diseases; (6) participants who were included in other clinical trials that would affect the assessments of outcomes in our study.
After obtaining participants’ written informed consent form and screening for inclusion and exclusion, all patients included were randomly assigned to computer-aided self-regulation learning group, demonstration learning group or traditional learning group in a ratio of 1:1:1. Randomization was conducted by an independent researcher who did not participate in intervention and outcomes assessments of our study. The randomized sequence was generated using simple randomization in SPSS 24.0 statistics analysis software. After completing baseline assessments, the independent researcher informed these patients about the results of their group allocation via telephone. Due to the full explanation of interventional contents to eligible participants in the informed consent form, it is impossible to blind these included patients. Outcome assessors, data entry personnel and statistical analysts were blinded to avoid potential bias. Meanwhile, to ensure the quality of training, all interventions were administered by occupational therapists who had over three years of working experience in post-stroke rehabilitation and did not participate in patients’ enrollments and outcome assessments. The schedule and contents of interventions in this study were shown in Figure 1.
Computer-aided self-regulation learning (CA-SRL) group
Patients in the CA-SRL group received CA-SRL training, CACT and basic activities of daily living (ADL) training. In the first week, basic ADL training were conducted for an hour per time with five sessions, which was the basis of SRL training. Through the first-week training, patients could be able to understand the contents involved in SRL training. This way was trying to avoid the potential effect of incomprehension of training contents that limit the efficacy of CA-SRL training. The contents of CA-SRL (including ten tasks that related to ADL) were performed for an hour per session five times per week in the next two weeks. In addition, the CACT training was carried out throughout the three weeks for 30 minutes each session.
Demonstration learning (DL) group
Training tasks in the DL group were also divided into three parts. In the first week, patients received the same basic ADL training with the same training dose. Unlike the CA-SRL group, these ten training tasks were conducted in a demonstration learning way with the same training schedule. Moreover, CACT was also conducted throughout these three weeks for 30 minutes each session.
Traditional learning (TL) group
Similar to the training schedule in the DL group, patients in the TL group received traditional cognitive training with the same training dose rather than CACT. Besides, other training parts (basic ADL training and DL training) were the same as the schedule of the DL group.
Computer-aided self-regulation learning training
There are three parts to the learning tasks of CA-SRL: step decomposition, self-calibration and mental imagery.25 As our design, CA-SRL recorded the process of patients’ task learning by cameras. Then the videos were displayed to make them self-reflected on their task performance.14,26 Moreover, there are ten daily tasks in CA-SRL training,27 including fold the laundry, see the doctor, make the bed, tidy the table after a meal, fry vegetables with meat, prepare fruit, sweep the floor, wash the dishes, change the beds and intake medication. In the CA-SRL training, therapists have guided patients for the pre-programmed instructions to understand the task's actions, self-reflection and think about the solution, and finally complete the tasks. In the second week, patients were trained in five daily tasks: fold the laundry, see the doctor, make the bed, tidy the table after a meal, fry vegetables with meat. Then in the third week, patients were trained with the other five tasks: wash the dishes, change the beds, prepare fruit, take medication and sweep the floor.
Computer-aided cognitive training
In this study, the contents of CACT were developed by the cognitive rehabilitation research team of Hong Kong Polytechnic University, Hong Kong University and Fujian University of Traditional Chinese Medicine. There were two parts of CACT named basic cognitive module and cognitive application module. The primary cognitive module contained simple reaction time, visual perception, visual attention, visual choice, sustained attention, working memory, maze, one mind for two purposes, psychological rotation and auditory choice, which aimed to improve specific cognitive function. Besides, the cognitive application module was composed by four parts: ability of computer application training, memory application training, logic ability training and attention application training. These training items are purposed to integrate the cognitive training contents into the living scenes for improving comprehensive cognitive abilities. As designed, professional therapists were appointed to arrange the training contents according to the actual situation of patients.
Demonstration learning training
There were three steps in DL training, consisted of step decomposition, error-less calibration and repetitive training.28 Manipulation of tasks (main steps, needed tools and sequence) would be told in details to patients to make a comparison for error-less calibration. Before completion of all tasks, therapists would give patients enough demonstrations and correct their inaccurate actions timely. Then, patients should practice this item repeatedly until completion of the task independently.29 All training contents were consistent with CA-SRL contents.
Basic ADL training
The professional therapists would conduct the basic activities of daily living training based on the Code of Practice for Common Rehabilitation Therapy Techniques (2012 edition). The training contents included clothing, decoration, eating, bed and chair transfer, going to the toilet, bathing, and going up and downstairs. According to the conditions and performances of patients, occupational therapists would evaluate patients’ activities and then prepare the corresponding tools such as clothes for dressing and spoons for eating. Through observations and evaluations, the missing components of their actions would be told to patients, and then these actions should be trained repeatedly.
Traditional cognitive training
Based on the Code of Practice for Common Rehabilitation Therapy Techniques (2012 edition), the contents of the traditional cognitive training were composed of attention, memory, calculation and discrimination training. Therapists were appointed to conduct traditional cognitive training for the patients according to their results of cognitive assessment.
The primary outcomes were Daily Living Task Assessment 27 and Montreal Cognitive Assessment (MoCA), Fuzhou version.23 Daily Living Task Assessment was applied to assess the abilities to relearn and generalization (Reliability: 0.89-0.98, kappa value: 0.54-0.72).27 In the relearning test, the previous five trained tasks (wash the dishes, change the beds, prepare fruit, take medication and sweep the floor) were used. Another five untrained daily tasks (including cook and steam fish, put clothes on a hanger, use the telephone, go to the canteen and clean the bathroom) were conducted to assess the generalization ability. These subtests were both scoring from 1 (total assistance, unable to perform 25% or more of task) to 7 (complete independence, perform a task in a timely and safe manner).27 Higher score means more extraordinary ability in independence. MoCA was used to assess the global cognitive function.
The secondary outcomes were Modified Barthel Index (MBI) 30, Lawton Instrumental Activity of Daily Living Scale (IADLs) 31,32and Simplified Fugl-Meyer Assessment (FMA) 33. MBI and IADLs were applied to evaluate patients' ability of basic ADL and instrumental ADL, respectively. FMA was used to assess the motor functions of post-stroke patients.
Except for evaluating the generalization ability after intervention, other outcomes were all assessed at baseline and post-intervention after three weeks. All data included in the analysis were calculated by IBM SPSS Version 24.0 software. The categorical variables were expressed in numbers by several different categories using Chi-square (c2) tests. The continuous variables were presented in the form of Mean±Standard Deviation (SD) and calculated according to their types of distribution. If these continuous variables were in a normal distribution, a one-way analysis of covariance (ANCOVA) would be applied to compare the differences between these three groups. Otherwise, Kruskal-Wallis rank-sum test would be applied.
Moreover, to clarify the efficacy of the intervention, differences between baseline and after intervention would be compared by paired t-test or Wilcoxon signed-rank test. Due to the significant difference of education and scores of IADLs across three groups at baseline, these factors were added as covariates in ANCOVA for multiple comparisons. P-values below 0.05 (two-tailed) were considered statistically significant.