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Comprehensive Rehabilitation Training Decreases Cognitive Impairment, Anxiety, and Depression in Poststroke Patients: A Randomized, Controlled Study
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Comprehensive Rehabilitation Training Decreases Cognitive Impairment, Anxiety, and Depression in Poststroke Patients: A Randomized, Controlled Study D1X XChunmei Cheng, D2XMM, X * D3X XXin Liu, MM, D4X X † D5X XWenjun Fan, D6XBA, X * D7X XXue Bai, BA, D8X X * and D9X XZhaojun Liu, MM D10X X * Background: To explore the effect of comprehensive rehabilitation training (CRT) on cognitive impairment, anxiety, and depression in poststroke patients. Methods: 168 poststroke patients were consecutively recruited in this randomized controlled study. Patients were randomly assigned to CRT group (CRT plus conventional treatment) and control group (conventional treatment) as 1:1 ratio. The specific interventions of CRT included patient and family member education, cognitive training, rehabilitation training, and regular check. Results: Both montreal cognitive assessment score change (Month12 [M12]-baseline; P = .001) and minimum mental state examination score change (M12-baseline) were higher in CRT group than that in control group (P = .004), and the percentage of cognitive impairment by montreal cognitive assessment score 26 was lower (P = .003) in CRT group compared to control group at month 12. Anxiety assessments were performed by hospital anxiety and depression scale (HADS) and Zung self-rating anxiety scale (SAS). The HADS anxiety score change (M12-baseline; P = .002) and the SAS score change (M12-baseline; P = .006) were decreased in CRT group compared to control group. Lower occurrence rate of anxiety assessed by SAS was observed in CRT group compared to control group (P = .033). Depression assessments were performed by HADS and Zung self-rating depression scale (SDS). HADS depression score change (M12-baseline; P < .001) and the SDS score change (M12-baseline; P = .002) were reduced in CRT group compared to control group. Decreased occurrence rate of depression assessed by SDS was found in CRT group compared to control group (P = .022). Conclusions: CRT contributes to the recovery of cognitive impairment, and decreases anxiety and depression in poststroke patients. Key Words: CRT—cognitive impairment—anxiety—depression—poststroke patients © 2018 Published by Elsevier Inc. on behalf of National Stroke Association.
Introduction Stroke, one of the most common and serious global health-care problem, is defined as an acute episode of From the *Department of Neurology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China; and †Department of Rehabilitation, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China. Received January 8, 2018; revision received May 18, 2018; accepted May 22, 2018. Address correspondence to Zhaojun Liu, MM, Department of Neurology, The 2nd Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, China. E-mail: [email protected] 1052-3057/$ - see front matter © 2018 Published by Elsevier Inc. on behalf of National Stroke Association. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.05.038
focal dysfunction in brain, retina, or spinal cord owning to infarction or haemorrhage, whose symptoms persist longer than 24 hours.1 2017 heart disease and stroke statistics has proven that approximately 6.5 million stroke deaths occur worldwide in 2013, which make stroke no. 2 among all causes of deaths only behind ischemic heart disease.2 In United States, every 40 seconds on average, someone occurs a stroke, and every 4 minutes on average, someone dies of a stroke.2 Despite of impressive developments of early diagnosis and medical management which result in the decrease of incidence and mortality rates of stroke, about 25%-74% stroke patients still suffer life-long disability and severe psychological illness, including cognitive impairment, anxiety, and depression.3,4 Due to motor and sensory impairments, which leads to life-long
Journal of Stroke and Cerebrovascular Diseases, Vol. &&, N0. && (&&), 2018: pp 1-10
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disability and limitation of activities of daily living (ADL), many stroke patients are difficult to accept these sequelae and easy to lose confidence, or even have inferiority complex, thereby resulting in the increase of anxiety and depression. Hence, investigating stroke rehabilitation interventions are necessary to improve patients’ mental health and increase their quality of life after stroke. Stroke rehabilitation, described as a stroke-care intervention, is designed to decrease the disability and handicap due to a stroke.5 Based on several previous studies, much of attention in stroke rehabilitation training is on the recovery of impaired movement and the associated functions.6,7 However little is known about the role of comprehensive rehabilitation training (CRT) in the prognosis of poststroke patients, especially in psychological illness including cognitive impairment, depression, and anxiety. Thus, we designed a novel CRT, which was a complex rehabilitation programme including patient and family member education, cognitive training, rehabilitation training, as well as regular check, and the purpose of this study was to explore the efficacy of CRT on cognitive impairment, anxiety, and depression in poststroke patients.
Methods Participants A total of 168 patients who were initially diagnosed as ischemic stroke admitted in The 2nd Affiliated Hospital of Harbin Medical University from July 2014 to June 2016 were consecutively recruited in this randomized controlled study. All patients aged 18 years or older with a clinical diagnosis of ischemic stroke confirmed by brain computed tomography or magnetic resonance imaging, and had no history of stroke and no serious visual or hearing impairment, mental disorders that effect cognitive examination. Potential patients who met any of the following criteria were excluded from participating in the study: (1) Suffering from obvious cognitive impairment, mental decline, or dementia prior to the onset of ischemic stroke; (2) Unlikely to complete the cognitive, anxiety, and depression assessment within 7 days after stoke; (3) Life expectancy was less than 12 months; and (4) Combined with serious heart disease, liver or renal failure, malignant tumors, or other serious disease. The Ethics Committee of the 2nd Affiliated Hospital of Harbin Medical University had approved this study, and all patients provided signed informed consents.
Randomization In this randomized controlled study, patients were randomly assigned to CRT group or control group as 1:1 ratio. Randomization sequence was created using blocked randomization method by Zung self-rating anxiety scale (SAS) software. The randomization was conducted by a
statistical analyzer who was not involved in other parts of the study, and the documents were sent and kept in Shanghai Qeejen Bio-tech Company (a medical and statistic service company). When a patient was eligible for the study, a call was made to Qeejen Company and a unique subject identification number was provided from the randomized module.
Treatment In CRT group, patients received CRT, usual care, and conventional treatment, and CRT was performed when patients with stable physical station and without rapid progress within 48 hours. In the control group, patients only received the conventional treatment and usual care. All patients of 2 groups received treatment for 6 months and follow-up for 12 months. The specific interventions of CRT were as follows:
1. Patient and family member education: A manual of the Rehabilitation and Mental Health of Stroke, which included the understanding of stroke, influence by stroke, common issues, physical care, mental care, and so on, developed by our hospital was dispensed to the patients and their families for comprehensive education in the first 2 weeks after enrollment, and then detailed instruction was given once every 2 months for 6 months. Moreover, there was a special phone number in rehabilitation department of our hospital setting for patients or their caregivers to resolve the issues they met during the period, if needed, a nurse specialized in poststroke care, rehabilitation specialist, or a social worker was sent to visit the patient or the family member to further deal with the problems. 2. Cognitive training: Related research therapist (a trained, licensed occupational therapist with expertise in stroke rehabilitation) would visit the patient to provide instructions on cognitive training including simple instruction training, oral and facial muscle mimic training and rehearsal training for the patients with obstacles such as listening, speaking, reading, writing, and retelling in 2 weeks after enrollment, and then once a month for 6 months. 3. Rehabilitation training: (1) Related research therapist would visit the patient to provide instructions to the relatives of the patient on massage and systemic coordinative training 2 weeks after enrollment, and then once every 2 months for 6 months. (2) Patients were instructed to visit the rehabilitation department of our hospital to
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receive rehabilitation training once a week for 6 months. The specific contents of rehabilitation training were shown in Supplementary Table S1. 4. Regular check: Patients were instructed to regularly undergo necessary biochemical examinations, including blood glucose, blood pressure, and blood lipid to manage any abnormality timely once every 2 months for 6 months. Usual care mainly included: (1) the conventional training such as keeping normal limb position, passive movement of hemiplegic limbs, activity on the bed, change posture regularly, standing and walk training, ADL, and so on; (2) maintain airway patency and pay attention to oral and skin cleanliness; (3) prevention of bedsore, infection, or hyper accumulating pneumonia; (4) dietary instructions; (5) strengthen the management of excretion; (6) prevention of adverse events; (7) psychological nursing; and (8) discharging guidance. Conventional treatment included thrombolytic therapy, antispasmodic therapy and prevention of deep venous thrombosis, and so on. Both usual care and conventional treatment were performed according to the Chinese Stroke Rehabilitation Therapy Guide (2011).8
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which were scored as 0-3 points individually, resulting in 0-21 points and being classified as: 0-7, no anxiety; 8-10, mild anxiety; 11-14, moderate anxiety; 15-21, severe anxiety.11 SAS consists of twenty questions which were scored as 1-4 points individually, resulting in 20-80 raw score, subsequently standard score was calculated by int (1.25*raw score) and classified as: 25-49, no anxiety; 50-59, mild anxiety; 60-69, moderate anxiety; 70-100, severe anxiety.12
Evaluation of Depression HADS depression score and Zung self-rating depression scale (SDS) score were used to assess the depression of patients, which were assessed at baseline, month 3, month 6, and month 12. HADS-D consists of 7 questions which were scored as 0-3 points individually, resulting in 0-21 points and being classified as: 0-7, no depression; 8-10, mild depression; 11-14, moderate depression; 15-21, severe depression.11 SDS consists of 20 questions which were scored as 1-4 points individually, resulting in 20-80 raw score, subsequently standard score was calculated by int (1.25*raw score) and classified as: 25-49, no depression; 50-59, mild depression; 60-69, moderate depression; 70100, severe depression.13
Information Collection Within 7 days after the onset of stroke, all patients’ demographic and clinical characteristics were collected, which included age, gender, education duration, lesion location, smoke, hypertension, hyperlipidemia, and diabetes. Moreover, demographic information such as age, gender, and education duration of family member who were selected as prior caregiver for the patients were collected as well.
Evaluation of Cognitive Impairment Montreal cognitive assessment (MOCA) score and minimum mental state examination (MMSE) score were used to assess the cognitive impairment of patients, which were assessed at baseline, month 3, month 6, and month 12. The MOCA assessed short-term memory recall, visuospatial abilities, executive function, verbal abstraction, attention, concentration, working memory, language, and orientation, and the MMSE assessed orientation, learning and recall of words, and copy of a simple geometric figure. Scores on both screeners range from 0 to 30 points, with a lower score reflecting greater cognitive impairment, and a cut-off of <26 on the MOCA and MMSE was considered as indicative of cognitive impairment.9,10
Evaluation of Anxiety Hospital anxiety and depression scale (HADS) anxiety score andSAS score were applied to assess anxiety of patients, which were assessed at baseline, month 3, month 6 and month 12. HADS-anxiety consists of 7 questions
Statistics Statistics analyses were performed by using SPSS 22.0 software (IBM) and office 2010 software (IBM). Data were presented as mean value § standard deviation, mean § standard deviation, median (1/4 to 3/4 quarter) or count (percentage). Comparison between 2 groups was determined by t test, Wilcoxon rank sum test or chi-square test. P < .05 (shown as *) was considered significant, P < .01 (shown as **) was considered high significant, P < .001 (shown as ***) was considered very high significant. NS means no significance.
Results Study Flow A total of 201 stroke patients were screened for eligibility, and then 33 cases were excluded, including 23 cases who did not meet the inclusion criteria and 10 cases who were disagreed to sign informed consents (Fig 1). The remaining 168 cases were randomized as 1:1 radio, among these, 84 cases were treated with CRT plus conventional treatment as CRT group, and another 84 cases were treated with conventional treatment as control group. In CRT group, there were 15 total withdrawals, including 2 cases who made decision by patients or family member, 4 cases who were unable to be assessed during the study, 3 cases who lost follow-up, 3 cases who were hospitalized again by cerebral infarction and 3 deaths, causing 69 cases (82%) who completed 12-month follow-ups. As to control group, totally 17 cases withdrew during the study,
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Figure 1. Study flow.
including 1 case who made decision by patients or family member, 5 cases who were unable to be assessed during the study, 5 cases who lost follow-up, and 3 cases who were hospitalized again by cerebral infarction and 4 deaths, thereby leading to 67 cases who completed 12month follow-ups (79%). In the current study, Intent-totreat (ITT) analysis was performed, and as to patients who did not complete the whole study, the evaluation indexes at the last follow-up were used as the value of each later missing visit.
Baseline Characteristics of Poststroke Patients There was no difference in demographic features, clinical characteristics, and caregiver's conditions between CRT group and control group (all P > .05; Table 1). Mean age of stroke patients in CRT group and control group was 63.36 § 9.08 years and 63.11 § 11.95 years respectively. The number of stroke patients with hypertension, hyperlipidaemia, and diabetes was 70 (83.3%), 53 (63.1%), and 16 (19.0%) respectively in CRT group, and 64 (76.2%), 50 (59.5%), and 20 (23.8%) respectively in control group. The mean value of MOCA score, MMSE score, HADS-Anxiety score, SAS score, and SDS score was 25.2 § 3.3, 27.2 § 2.5, 6.3 § 4.1, 6.8 § 4.6, 42.9 § 10.0, and 44.7 § 12.5 respectively in CRT group, and 24.6 § 4.4, 27.1 § 2.7, 6.1 § 4.3, 6.4 § 4.2, 41.2 § 11.0, and 44.0 § 12.0 respectively in
control group. Other baseline characteristics were shown in Table 1.
Comparison of MOCA Score Between CRT Group and Control Group There was no difference in MOCA score at baseline and month 3 between CRT group and control group, while the mean value of MOCA score in CRT group was higher than that in control group at month 6 (P < .05) and month 12 (P < .001; Fig 2, A). In addition, the mean value of MOCA score change (M12-baseline) was higher in CRT group (1.5 § .29) compared to control group (.19 § .28; P = .001; Fig 2, B). As to the percentage of cognitive impairment defined as MOCA score 26, there was no difference at baseline between 2 groups (P = .738), while it was lower at month 12 in CRT group compared to control group (P = .003; Fig 2, C).
Comparison of MMSE Score Between CRT Group and Control Group No difference in MMSE score at each visit (baseline, month 3, month 6, and month12) was found between CRT group and control group (Fig 3, A). The MMSE score change (M12-baseline) was higher (.44 § .17) in CRT group than that in control group (¡.24 § .15; P = .004; Fig 3, B). As to the percentage of cognitive impairment by MMSE score 26, no difference was observed at baseline
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Table 1. Baseline characteristics of poststroke patients Items Age (years) Gender (male, n/%) Education duration (years) Lesion location (n/%) Left Right Bilateral/brainstem/unknown Smoke (n/%) Hypertension (n/%) Hyperlipidemia (n/%) Diabetes (n/%) MOCA score MOCA 26 (cognitive impairment, n/%) MOCA > 26 (n/%) MMSE score MMSE 26 (cognitive impairment, n/%) MMSE > 26 (n/%) HADS-anxiety score No anxiety (HADS-anxiety 7, n/%) Anxiety (HADS-anxiety > 7, n/%) HADS-depression score No depression (HADS-depression 7, n/%) Depression (HADS-depression > 7, n/%) SAS score No anxiety (SAS49, n/%) Anxiety (SAS>50, n/%) SDS score No depression (SAS49, n/%) Depression (SAS > 50, n/%) Caregiver Age (years) Gender (male, n/%) Education duration (years)
CRT group (N = 84)
Control group (N = 84)
P value
63.36 § 9.08 39 (46.4) 6.5 (5.0-10.0)
63.11 § 11.95 44 (52.4) 7.0 (4.0-9.0)
0.879 0.440 0.482 0.432
31 (36.9) 26 (31.0) 27 (32.1) 21 (25.0) 70 (83.3) 53 (63.1) 16 (19.0) 25.2§3.3 46 (54.8) 38 (45.2) 27.2 § 2.5 21 (25.0) 63 (75.0) 6.3 § 4.1 63 (75.0) 21 (25.0) 6.8 § 4.6 55 (65.5) 29 (34.5) 42.9 § 10.0 65 (77.4) 19 (22.6) 44.7 § 12.5 58 (69.0) 26 (31.0)
32 (38.1) 32 (38.1) 20 (23.8) 18 (21.4) 64 (76.2) 50 (59.5) 20 (23.8) 24.6§4.4 44 (52.4) 40 (47.6) 27.1 § 2.7 23 (27.4) 61 (72.6) 6.1 § 4.3 63 (75.0) 21 (25.0) 6.4 § 4.2 65 (77.4) 19 (22.6) 41.2 § 11.0 65 (77.4) 19 (22.6) 44.0 § 12.0 63 (75.0) 21 (25.0)
47.6 § 12.7 32 (38.1) 10.0 (7.0-14.0)
46.6 § 10.4 34 (40.5) 11.0 (8.0-14.0)
0.584 0.249 0.635 0.542 0.348 0.738 0.860 0.726 0.702 1.000 0.565 0.088 0.285 1.000 0.717 0.390
0.577 0.752 0.158
Abbreviations: CRT, comprehensive rehabilitation training; HADS, hospital anxiety and depression scale; MOCA, montreal cognitive assessment (MOCA); MMSE, minimum mental state examination; SAS, zung self-rating anxiety scale; SDS, zung self-rating depression scale. Data were presented as mean value § standard deviation, median (1/4 to 3/4 quarter) or count (percentage). Difference was determined by t test, Wilcoxon rank sum test or chi-square test. P value < .05 was considered significant.
(P = .726) and month 12 (P = .062) between CRT group and control group (Fig 3, C). In addition, the comparisons of ADL score at M0, M3, M6, and M12, as well as the changes of ADL score (M12-M0) between CRT group and control group were performed, and the detailed information were shown in Supplementary Table S2.
Comparison of Anxiety Scores by HADS and SAS Scales Between CRT Group and Control Group Two scales for anxiety assessments were performed including HADS and SAS. No difference in HADS anxiety score at baseline, month 3, month 6, and month12 between CRT group and control group (all P > .05; Fig 4, A). In addition, the HADS anxiety score change (M12baseline) was decreased in CRT group (¡.23 § .20)
compared to control group (.62 § .17; P = .002; Fig 4, B). As for SAS score, there was no difference in SAS score at baseline, month 3 and month 6 between 2 groups (all P > .05), while SAS score was lower in CRT group than that in control group (P < .05; Fig 4, C). In addition, the SAS score change (M12-baseline) was decreased in CRT group (¡.23 § .20) compared to control group (2.00 § .77; P = .006; Fig 4, D). Furthermore, analysis of anxiety grade after treatment was assessed (Fig 5; Supplementary Table S3.). No difference was found in the occurrence rate of anxiety assessed by HADS-anxiety between 2 groups (Fig 5, A), while lower occurrence rate of anxiety assessed by SAS was observed in CRT group compared to control group (P = .033; Fig 5, B). As to grade, no difference in the number of patients with light,
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Figure 2. Comparison of MOCA score between CRT group and control group. No difference in MOCA score at baseline and month 3 between groups, while the mean value of MOCA score in CRT group was higher than that in control group at month 6 and month 12 (A). The MOCA score change (M12-baseline) was higher in CRT group compared to control group (B). No difference was found in the percentage of cognitive impairment by MOCA score 26 at baseline between 2 groups, while it was lower at month 12 in CRT group compared to control group (C). Data were presented as mean § SD. Comparisons of MOCA score at each visit and the MOCA score change (M12-baseline) were determined by t test (error bars presented as SD). Comparison of the percentage of cognitive impairment by MOCA score 26 was determined by chi-square test. *P < .05, **P < .01, ***P < .001, NS means no significance. Abbreviations: CRT, comprehensive rehabilitation training; MOCA, montreal cognitive assessment; SD, standard deviation.
moderate, and severe HADS-anxiety grade (Fig 5, C) and SAS grade (Fig 5, D) between 2 groups was observed (all P > .05).
Comparison of Depression Scores by HADS and SDS Scales Between CRT Group and Control Group Two scales for depression assessments were performed including HADS and SDS. As shown in Figure 6, there was no difference in HADS depression score at each visit between 2 groups (all P > .05; Fig 6, A). As to HADS depression score change (M12-baseline), it was decreased in CRT group (¡.71 § .23) compared to control group (.44 § .18; P < .001; Fig 6, B). As to SDS score, no difference in SDS score between CRT group and control group at baseline, month 3 and month 6 (P > .05), while it was lower at month 12 in CRT group compared to control group (P < .05; Fig 6, C). The SDS score change (M12-baseline) was decreased in CRT group (¡2.10 § 1.10) compared to control group (2.30 § .88; P = .002; Fig 6, D).
Furthermore, there was no difference in the occurrence rate of depression assessed by HADS-depression between CRT and control groups (Fig 7, A), while decreased occurrence rate of depression assessed by SDS was found in CRT group compared to control group (P = .022; Fig 7, B; Supplementary Table S4). As to grade, no difference in the number of patients with light, moderate, and severe HADS-depression grade (Fig 7, C) and SDS grade (Fig 7, D) between 2 groups was observed (all P > .05).
Discussion In the current study, we observed that (1) CRT decreased cognitive impairment assessed by MOCA score and MMSE score; (2) CRT reduced anxiety assessed by HADS anxiety score and SAS score; and (3) CRT contributed to the anesis of depression evaluated by HADS depression score and SDS score in poststroke patients. There was no difference in these results between ITT
Figure 3. Comparison of MMSE score between CRT group and control group. No difference in MMSE score at each visit was found between groups (A). The MMSE score change (M12-baseline) was higher in CRT group than that in control group (B). No difference was observed in the percentage of cognitive impairment by MMSE score 26 at baseline and month 12 between groups (C). Data were presented as mean § SD. Comparisons of MMSE score at each visit and the MMSE score change (M12-baseline) were determined by t test (error bars presented as SD). Comparison of the percentage of cognitive impairment by MMSE score 26 was determined by chi-square test. *P < .05, **P < .01, ***P < .001, NS means no significance. Abbreviations: CRT, comprehensive rehabilitation training; MMSE, minimum mental state examination; SD, standard deviation.
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Figure 4. Comparison of HADS anxiety score and SAS score between CRT group and control group. No difference in HADS anxiety score at each visit between groups (A). The HADS anxiety score change (M12-baseline) was decreased in CRT group compared to control group (B). No difference was observed in SAS score at baseline, month 3 and month 6 between 2 groups, while SAS score was lower in CRT group than that in control group at month 12 (C). The SAS score change (M12-baseline) was decreased in CRT group compared to control group (D). Data were presented as mean § SD and difference was determined by t test (error bars presented as SD). *P < .05, **P < .01, ***P < .001, NS means no significance. Abbreviations: CRT, comprehensive rehabilitation training; HASD, hospital anxiety and depression scale; SD, standard deviation.
Figure 5. Comparison of anxiety scores by HADS and SAS scales between CRT group and control group No difference was found in the occurrence rate of anxiety assessed by HADS-anxiety between 2 groups (A), while lower occurrence rate of anxiety assessed by SAS was observed in CRT group compared to control group (B). No difference in the number of patients with light, moderate and severe HADS-anxiety grade (C) and SAS grade (D) between 2 groups was observed. Comparison was performed by chi-square test or Wilcoxon rank sum test. P < .05 was considered significant. Abbreviations: CRT, comprehensive rehabilitation training; HASD, hospital anxiety and depression scale; SAS, Zung self-rating anxiety scale.
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Figure 6. Comparison of HADS depression score between CRT group and control group. No difference was found in HADS Depression score at each visit between 2 groups (A). The HADS Depression score change (M12-baseline) was decreased in CRT group compared to control group (B). No difference in SDS score between groups at baseline, month 3 and month 6, while it was lower at month 12 in CRT group compared to control group (C). The SDS score change (M12-baseline) was decreased in CRT group compared to control group (D). Data were presented as mean § SD and difference was determined by t test (error bars presented as SD). *P < .05, **P < .01, ***P < .001, NS means no significance. Abbreviations: CRT, comprehensive rehabilitation training; HASD, hospital anxiety and depression scale; SD, standard deviation; SDS, Zung self-rating depression scale.
Figure 7. Comparison of depression scores by HADS and SDS scales between CRT group and control group. There was no difference in the occurrence rate of depression assessed by HADS-depression between CRT and control groups (A), while decreased occurrence rate of depression assessed by SDS was found in CRT group compared to control group (B). No difference in the number of patients with light, moderate and severe HADS-depression grade (C) and SDS grade (D) between 2 groups was observed. Comparison was performed by chi-square test or Wilcoxon rank sum test. P < 0.05 was considered significant. Abbreviations: CRT, comprehensive rehabilitation training; HASD, hospital anxiety and depression scale; SDS, Zung self-rating depression scale.
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analysis and per-protocol analysis in this randomized controlled study. Effective rehabilitation interventions which are early initiated, promote the recovery effectiveness and minimize functional disability in poststroke patients.14 Accumulating evidence have proven that stroke rehabilitation plays an important role in the improvement of motor function in patients with subacute stroke, a first episode of ischemic stroke, spastic quadriplegia, and neuropsychiatric systemic lupus erythematosus.15-18 As for sensory function, including cognitive impairment that is one of common sequelae after stroke, one previous study discloses that after regular rehabilitation, both of MMSE and MOCA score are increased apparently, which are better than that in control group, suggesting that stroke rehabilitation obviously improve the cognitive function in poststroke patients.19 Another study indicates that computerbased cognitive rehabilitation program contributes toward the recovery of cognitive function and visual perception in acute stroke patients.20 Although these previous studies identify that some stroke rehabilitations obviously improve the cognitive function in poststroke patients, limited information about the role of CRT in cognitive impairment after stroke. In the present study, we designed a novel CRT programme, a complex rehabilitation program being individualized according to the initial evolutionary stage, motor impairment, and psychiatric disorders, and we applied MMSE and MOCA as evaluation tools and we observed that CRT contributed to the anesis of cognitive impairment in poststroke patients. The possible reasons were as follows: (1) CRT, consisting of patient and family member education, cognitive training, rehabilitation training as well as regular check, is a complex rehabilitation program to comprehensively train motor and sensory function, thereby promoting stroke rehabilitation and decreasing cognitive impairment. (2) CRT is a cyclical process involving: assessment, goal setting, intervention, and reassessment, which could increase the awareness of patients, caregivers, and nurses to clearly know the state of illness and intimately observe the illness changes, thereby minimising stroke complications and reducing cognitive impairment in poststroke patients. After a stroke, much of patients suffer motor and sensory impairments, which limit their mobility, self-care ability, and social participation, thereby making them losing their confidence, increasing risk of anxiety, and depression.21 There are several previous studies, which have proven the positive effects of stroke rehabilitation on motor function after stroke, while few studies have been performed related to the role of CRT, which is a comprehensive rehabilitation program involving in motor training, sensory training as well as regular psychological assessment, in the anxiety and depression of poststroke patients.7,16,17 Hence, in the present study, we designed CRT and investigated the effects of CRT on anxiety and depression assessed by HADS score and SAS/SDS score
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in poststroke patients, and we found that CRT could decrease anxiety and depression in poststroke patients. The possible reasons were that (1) CRT contributes to the recovery of motor and sensory impairments, and its longterm improvement of ADL ability provide patients with new hope, thereby increasing their confidence and decreasing anxiety as well as depression in poststroke patients. (2) CRT, which is a training completed by patients with assistance of caregivers and nurses, increases communication time among them, maintaining a good environment with more understanding and cooperation, thereby promoting the regulation of mental health and reducing the anxiety as well as depression in poststroke patients. There were still some limitations in this study. First, the follow-up duration was relatively short, it was 12 months in this study, which did not investigate the long-term effects of CRT on cognitive impairment, anxiety, and depression in poststroke patients. Second, the sample size in this study was relatively small, which only enrolled 84 patients in CRT group and 84 patients in control group, thus, the statistics power might be low. Third, this study was a single institutional study, and all patients were from monocentric, thus, further study with more patients from multicenter is necessary. In conclusion, CRT contributes to the recovery of cognitive impairment, and decreases anxiety and depression in poststroke patients. Conflict of Interest: conflict of interest.
The authors declare that they have no
Supplementary Materials Supplementary data to this article can be found online at doi:10.1016/j.jstrokecerebrovasdis.2018.05.038.
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multicenter randomized controlled trial. BMC Complement Altern Med 2016;16:226. Chinese stroke rehabilitation guide (2011 edition). Chin J Rehabil Theory Pract. 2012;18:301-318. Hawkins MA, Gathright EC, Gunstad J, et al. The MoCA and MMSE as screeners for cognitive impairment in a heart failure population: a study with comprehensive neuropsychological testing. Heart Lung 2014;43:462-468. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-198. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361-370. Gainotti G, Cianchetti C, Taramelli M, et al. The guided self-rating anxiety-depression scale for use in clinical psychopharmacology. Act Nerv Super 1972;14:49-51. Zung WW, Gianturco JA. Personality dimension and the self-rating depression scale. J Clin Psychol 1971;27:247-248. Duncan PW, Zorowitz R, Bates B, et al. Management of adult stroke rehabilitation care: a clinical practice guideline. Stroke 2005;36:e100-e143. Rogoveanu OC, Tutescu NC, Kamal D, et al. The benefits of a comprehensive rehabilitation program in patients diagnosed with spastic quadriplegia. J Med Life 2016;9:263-269.
16. Fang J, Chen L, Ma R, et al. Comprehensive rehabilitation with integrative medicine for subacute stroke: A multicenter randomized controlled trial. Sci Rep 2016;6:25850. 17. Starosta M, Niwald M, Miller E. The effectiveness of comprehensive rehabilitation after a first episode of ischemic stroke. Pol Merkur Lekarski 2015;38:254-257. 18. Ko YJ, Lee YG, Park JW, et al. A comprehensive rehabilitation approach in a patient with serious neuropsychiatric systemic lupus erythematosus. Ann Rehabil Med 2016;40:745-750. 19. Zhan J, Pan R, Guo Y, et al. Acupuncture at Baihui(GV 20) and Shenting(GV 24) combined with basic treatment and regular rehabilitation for post-stroke cognitive impairment:a randomized controlled trial. Zhongguo Zhen Jiu 2016;36:803-806. 20. Park JH, Park JH. The effects of a Korean computer-based cognitive rehabilitation program on cognitive function and visual perception ability of patients with acute stroke. J Phys Ther Sci 2015;27:2577-2579. 21. Hatem SM, Saussez G, Della Faille M, et al. Rehabilitation of motor function after stroke: a multiple systematic review focused on techniques to stimulate upper extremity recovery. Front Hum Neurosci 2016;10:442.
Comprehensive Rehabilitation Training Decreases Cognitive Impairment, Anxiety, and Depression in Poststroke Patients: A Randomized, Controlled Study D1X XChunmei Cheng, D2XMM, X * D3X XXin Liu, MM, D4X X † D5X XWenjun Fan, D6XBA, X * D7X XXue Bai, BA, D8X X * and D9X XZhaojun Liu, MM D10X X * Background: To explore the effect of comprehensive rehabilitation training (CRT) on cognitive impairment, anxiety, and depression in poststroke patients. Methods: 168 poststroke patients were consecutively recruited in this randomized controlled study. Patients were randomly assigned to CRT group (CRT plus conventional treatment) and control group (conventional treatment) as 1:1 ratio. The specific interventions of CRT included patient and family member education, cognitive training, rehabilitation training, and regular check. Results: Both montreal cognitive assessment score change (Month12 [M12]-baseline; P = .001) and minimum mental state examination score change (M12-baseline) were higher in CRT group than that in control group (P = .004), and the percentage of cognitive impairment by montreal cognitive assessment score 26 was lower (P = .003) in CRT group compared to control group at month 12. Anxiety assessments were performed by hospital anxiety and depression scale (HADS) and Zung self-rating anxiety scale (SAS). The HADS anxiety score change (M12-baseline; P = .002) and the SAS score change (M12-baseline; P = .006) were decreased in CRT group compared to control group. Lower occurrence rate of anxiety assessed by SAS was observed in CRT group compared to control group (P = .033). Depression assessments were performed by HADS and Zung self-rating depression scale (SDS). HADS depression score change (M12-baseline; P < .001) and the SDS score change (M12-baseline; P = .002) were reduced in CRT group compared to control group. Decreased occurrence rate of depression assessed by SDS was found in CRT group compared to control group (P = .022). Conclusions: CRT contributes to the recovery of cognitive impairment, and decreases anxiety and depression in poststroke patients. Key Words: CRT—cognitive impairment—anxiety—depression—poststroke patients © 2018 Published by Elsevier Inc. on behalf of National Stroke Association.
Introduction Stroke, one of the most common and serious global health-care problem, is defined as an acute episode of From the *Department of Neurology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China; and †Department of Rehabilitation, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China. Received January 8, 2018; revision received May 18, 2018; accepted May 22, 2018. Address correspondence to Zhaojun Liu, MM, Department of Neurology, The 2nd Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, China. E-mail: [email protected] 1052-3057/$ - see front matter © 2018 Published by Elsevier Inc. on behalf of National Stroke Association. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.05.038
focal dysfunction in brain, retina, or spinal cord owning to infarction or haemorrhage, whose symptoms persist longer than 24 hours.1 2017 heart disease and stroke statistics has proven that approximately 6.5 million stroke deaths occur worldwide in 2013, which make stroke no. 2 among all causes of deaths only behind ischemic heart disease.2 In United States, every 40 seconds on average, someone occurs a stroke, and every 4 minutes on average, someone dies of a stroke.2 Despite of impressive developments of early diagnosis and medical management which result in the decrease of incidence and mortality rates of stroke, about 25%-74% stroke patients still suffer life-long disability and severe psychological illness, including cognitive impairment, anxiety, and depression.3,4 Due to motor and sensory impairments, which leads to life-long
Journal of Stroke and Cerebrovascular Diseases, Vol. &&, N0. && (&&), 2018: pp 1-10
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disability and limitation of activities of daily living (ADL), many stroke patients are difficult to accept these sequelae and easy to lose confidence, or even have inferiority complex, thereby resulting in the increase of anxiety and depression. Hence, investigating stroke rehabilitation interventions are necessary to improve patients’ mental health and increase their quality of life after stroke. Stroke rehabilitation, described as a stroke-care intervention, is designed to decrease the disability and handicap due to a stroke.5 Based on several previous studies, much of attention in stroke rehabilitation training is on the recovery of impaired movement and the associated functions.6,7 However little is known about the role of comprehensive rehabilitation training (CRT) in the prognosis of poststroke patients, especially in psychological illness including cognitive impairment, depression, and anxiety. Thus, we designed a novel CRT, which was a complex rehabilitation programme including patient and family member education, cognitive training, rehabilitation training, as well as regular check, and the purpose of this study was to explore the efficacy of CRT on cognitive impairment, anxiety, and depression in poststroke patients.
Methods Participants A total of 168 patients who were initially diagnosed as ischemic stroke admitted in The 2nd Affiliated Hospital of Harbin Medical University from July 2014 to June 2016 were consecutively recruited in this randomized controlled study. All patients aged 18 years or older with a clinical diagnosis of ischemic stroke confirmed by brain computed tomography or magnetic resonance imaging, and had no history of stroke and no serious visual or hearing impairment, mental disorders that effect cognitive examination. Potential patients who met any of the following criteria were excluded from participating in the study: (1) Suffering from obvious cognitive impairment, mental decline, or dementia prior to the onset of ischemic stroke; (2) Unlikely to complete the cognitive, anxiety, and depression assessment within 7 days after stoke; (3) Life expectancy was less than 12 months; and (4) Combined with serious heart disease, liver or renal failure, malignant tumors, or other serious disease. The Ethics Committee of the 2nd Affiliated Hospital of Harbin Medical University had approved this study, and all patients provided signed informed consents.
Randomization In this randomized controlled study, patients were randomly assigned to CRT group or control group as 1:1 ratio. Randomization sequence was created using blocked randomization method by Zung self-rating anxiety scale (SAS) software. The randomization was conducted by a
statistical analyzer who was not involved in other parts of the study, and the documents were sent and kept in Shanghai Qeejen Bio-tech Company (a medical and statistic service company). When a patient was eligible for the study, a call was made to Qeejen Company and a unique subject identification number was provided from the randomized module.
Treatment In CRT group, patients received CRT, usual care, and conventional treatment, and CRT was performed when patients with stable physical station and without rapid progress within 48 hours. In the control group, patients only received the conventional treatment and usual care. All patients of 2 groups received treatment for 6 months and follow-up for 12 months. The specific interventions of CRT were as follows:
1. Patient and family member education: A manual of the Rehabilitation and Mental Health of Stroke, which included the understanding of stroke, influence by stroke, common issues, physical care, mental care, and so on, developed by our hospital was dispensed to the patients and their families for comprehensive education in the first 2 weeks after enrollment, and then detailed instruction was given once every 2 months for 6 months. Moreover, there was a special phone number in rehabilitation department of our hospital setting for patients or their caregivers to resolve the issues they met during the period, if needed, a nurse specialized in poststroke care, rehabilitation specialist, or a social worker was sent to visit the patient or the family member to further deal with the problems. 2. Cognitive training: Related research therapist (a trained, licensed occupational therapist with expertise in stroke rehabilitation) would visit the patient to provide instructions on cognitive training including simple instruction training, oral and facial muscle mimic training and rehearsal training for the patients with obstacles such as listening, speaking, reading, writing, and retelling in 2 weeks after enrollment, and then once a month for 6 months. 3. Rehabilitation training: (1) Related research therapist would visit the patient to provide instructions to the relatives of the patient on massage and systemic coordinative training 2 weeks after enrollment, and then once every 2 months for 6 months. (2) Patients were instructed to visit the rehabilitation department of our hospital to
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receive rehabilitation training once a week for 6 months. The specific contents of rehabilitation training were shown in Supplementary Table S1. 4. Regular check: Patients were instructed to regularly undergo necessary biochemical examinations, including blood glucose, blood pressure, and blood lipid to manage any abnormality timely once every 2 months for 6 months. Usual care mainly included: (1) the conventional training such as keeping normal limb position, passive movement of hemiplegic limbs, activity on the bed, change posture regularly, standing and walk training, ADL, and so on; (2) maintain airway patency and pay attention to oral and skin cleanliness; (3) prevention of bedsore, infection, or hyper accumulating pneumonia; (4) dietary instructions; (5) strengthen the management of excretion; (6) prevention of adverse events; (7) psychological nursing; and (8) discharging guidance. Conventional treatment included thrombolytic therapy, antispasmodic therapy and prevention of deep venous thrombosis, and so on. Both usual care and conventional treatment were performed according to the Chinese Stroke Rehabilitation Therapy Guide (2011).8
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which were scored as 0-3 points individually, resulting in 0-21 points and being classified as: 0-7, no anxiety; 8-10, mild anxiety; 11-14, moderate anxiety; 15-21, severe anxiety.11 SAS consists of twenty questions which were scored as 1-4 points individually, resulting in 20-80 raw score, subsequently standard score was calculated by int (1.25*raw score) and classified as: 25-49, no anxiety; 50-59, mild anxiety; 60-69, moderate anxiety; 70-100, severe anxiety.12
Evaluation of Depression HADS depression score and Zung self-rating depression scale (SDS) score were used to assess the depression of patients, which were assessed at baseline, month 3, month 6, and month 12. HADS-D consists of 7 questions which were scored as 0-3 points individually, resulting in 0-21 points and being classified as: 0-7, no depression; 8-10, mild depression; 11-14, moderate depression; 15-21, severe depression.11 SDS consists of 20 questions which were scored as 1-4 points individually, resulting in 20-80 raw score, subsequently standard score was calculated by int (1.25*raw score) and classified as: 25-49, no depression; 50-59, mild depression; 60-69, moderate depression; 70100, severe depression.13
Information Collection Within 7 days after the onset of stroke, all patients’ demographic and clinical characteristics were collected, which included age, gender, education duration, lesion location, smoke, hypertension, hyperlipidemia, and diabetes. Moreover, demographic information such as age, gender, and education duration of family member who were selected as prior caregiver for the patients were collected as well.
Evaluation of Cognitive Impairment Montreal cognitive assessment (MOCA) score and minimum mental state examination (MMSE) score were used to assess the cognitive impairment of patients, which were assessed at baseline, month 3, month 6, and month 12. The MOCA assessed short-term memory recall, visuospatial abilities, executive function, verbal abstraction, attention, concentration, working memory, language, and orientation, and the MMSE assessed orientation, learning and recall of words, and copy of a simple geometric figure. Scores on both screeners range from 0 to 30 points, with a lower score reflecting greater cognitive impairment, and a cut-off of <26 on the MOCA and MMSE was considered as indicative of cognitive impairment.9,10
Evaluation of Anxiety Hospital anxiety and depression scale (HADS) anxiety score andSAS score were applied to assess anxiety of patients, which were assessed at baseline, month 3, month 6 and month 12. HADS-anxiety consists of 7 questions
Statistics Statistics analyses were performed by using SPSS 22.0 software (IBM) and office 2010 software (IBM). Data were presented as mean value § standard deviation, mean § standard deviation, median (1/4 to 3/4 quarter) or count (percentage). Comparison between 2 groups was determined by t test, Wilcoxon rank sum test or chi-square test. P < .05 (shown as *) was considered significant, P < .01 (shown as **) was considered high significant, P < .001 (shown as ***) was considered very high significant. NS means no significance.
Results Study Flow A total of 201 stroke patients were screened for eligibility, and then 33 cases were excluded, including 23 cases who did not meet the inclusion criteria and 10 cases who were disagreed to sign informed consents (Fig 1). The remaining 168 cases were randomized as 1:1 radio, among these, 84 cases were treated with CRT plus conventional treatment as CRT group, and another 84 cases were treated with conventional treatment as control group. In CRT group, there were 15 total withdrawals, including 2 cases who made decision by patients or family member, 4 cases who were unable to be assessed during the study, 3 cases who lost follow-up, 3 cases who were hospitalized again by cerebral infarction and 3 deaths, causing 69 cases (82%) who completed 12-month follow-ups. As to control group, totally 17 cases withdrew during the study,
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Figure 1. Study flow.
including 1 case who made decision by patients or family member, 5 cases who were unable to be assessed during the study, 5 cases who lost follow-up, and 3 cases who were hospitalized again by cerebral infarction and 4 deaths, thereby leading to 67 cases who completed 12month follow-ups (79%). In the current study, Intent-totreat (ITT) analysis was performed, and as to patients who did not complete the whole study, the evaluation indexes at the last follow-up were used as the value of each later missing visit.
Baseline Characteristics of Poststroke Patients There was no difference in demographic features, clinical characteristics, and caregiver's conditions between CRT group and control group (all P > .05; Table 1). Mean age of stroke patients in CRT group and control group was 63.36 § 9.08 years and 63.11 § 11.95 years respectively. The number of stroke patients with hypertension, hyperlipidaemia, and diabetes was 70 (83.3%), 53 (63.1%), and 16 (19.0%) respectively in CRT group, and 64 (76.2%), 50 (59.5%), and 20 (23.8%) respectively in control group. The mean value of MOCA score, MMSE score, HADS-Anxiety score, SAS score, and SDS score was 25.2 § 3.3, 27.2 § 2.5, 6.3 § 4.1, 6.8 § 4.6, 42.9 § 10.0, and 44.7 § 12.5 respectively in CRT group, and 24.6 § 4.4, 27.1 § 2.7, 6.1 § 4.3, 6.4 § 4.2, 41.2 § 11.0, and 44.0 § 12.0 respectively in
control group. Other baseline characteristics were shown in Table 1.
Comparison of MOCA Score Between CRT Group and Control Group There was no difference in MOCA score at baseline and month 3 between CRT group and control group, while the mean value of MOCA score in CRT group was higher than that in control group at month 6 (P < .05) and month 12 (P < .001; Fig 2, A). In addition, the mean value of MOCA score change (M12-baseline) was higher in CRT group (1.5 § .29) compared to control group (.19 § .28; P = .001; Fig 2, B). As to the percentage of cognitive impairment defined as MOCA score 26, there was no difference at baseline between 2 groups (P = .738), while it was lower at month 12 in CRT group compared to control group (P = .003; Fig 2, C).
Comparison of MMSE Score Between CRT Group and Control Group No difference in MMSE score at each visit (baseline, month 3, month 6, and month12) was found between CRT group and control group (Fig 3, A). The MMSE score change (M12-baseline) was higher (.44 § .17) in CRT group than that in control group (¡.24 § .15; P = .004; Fig 3, B). As to the percentage of cognitive impairment by MMSE score 26, no difference was observed at baseline
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Table 1. Baseline characteristics of poststroke patients Items Age (years) Gender (male, n/%) Education duration (years) Lesion location (n/%) Left Right Bilateral/brainstem/unknown Smoke (n/%) Hypertension (n/%) Hyperlipidemia (n/%) Diabetes (n/%) MOCA score MOCA 26 (cognitive impairment, n/%) MOCA > 26 (n/%) MMSE score MMSE 26 (cognitive impairment, n/%) MMSE > 26 (n/%) HADS-anxiety score No anxiety (HADS-anxiety 7, n/%) Anxiety (HADS-anxiety > 7, n/%) HADS-depression score No depression (HADS-depression 7, n/%) Depression (HADS-depression > 7, n/%) SAS score No anxiety (SAS49, n/%) Anxiety (SAS>50, n/%) SDS score No depression (SAS49, n/%) Depression (SAS > 50, n/%) Caregiver Age (years) Gender (male, n/%) Education duration (years)
CRT group (N = 84)
Control group (N = 84)
P value
63.36 § 9.08 39 (46.4) 6.5 (5.0-10.0)
63.11 § 11.95 44 (52.4) 7.0 (4.0-9.0)
0.879 0.440 0.482 0.432
31 (36.9) 26 (31.0) 27 (32.1) 21 (25.0) 70 (83.3) 53 (63.1) 16 (19.0) 25.2§3.3 46 (54.8) 38 (45.2) 27.2 § 2.5 21 (25.0) 63 (75.0) 6.3 § 4.1 63 (75.0) 21 (25.0) 6.8 § 4.6 55 (65.5) 29 (34.5) 42.9 § 10.0 65 (77.4) 19 (22.6) 44.7 § 12.5 58 (69.0) 26 (31.0)
32 (38.1) 32 (38.1) 20 (23.8) 18 (21.4) 64 (76.2) 50 (59.5) 20 (23.8) 24.6§4.4 44 (52.4) 40 (47.6) 27.1 § 2.7 23 (27.4) 61 (72.6) 6.1 § 4.3 63 (75.0) 21 (25.0) 6.4 § 4.2 65 (77.4) 19 (22.6) 41.2 § 11.0 65 (77.4) 19 (22.6) 44.0 § 12.0 63 (75.0) 21 (25.0)
47.6 § 12.7 32 (38.1) 10.0 (7.0-14.0)
46.6 § 10.4 34 (40.5) 11.0 (8.0-14.0)
0.584 0.249 0.635 0.542 0.348 0.738 0.860 0.726 0.702 1.000 0.565 0.088 0.285 1.000 0.717 0.390
0.577 0.752 0.158
Abbreviations: CRT, comprehensive rehabilitation training; HADS, hospital anxiety and depression scale; MOCA, montreal cognitive assessment (MOCA); MMSE, minimum mental state examination; SAS, zung self-rating anxiety scale; SDS, zung self-rating depression scale. Data were presented as mean value § standard deviation, median (1/4 to 3/4 quarter) or count (percentage). Difference was determined by t test, Wilcoxon rank sum test or chi-square test. P value < .05 was considered significant.
(P = .726) and month 12 (P = .062) between CRT group and control group (Fig 3, C). In addition, the comparisons of ADL score at M0, M3, M6, and M12, as well as the changes of ADL score (M12-M0) between CRT group and control group were performed, and the detailed information were shown in Supplementary Table S2.
Comparison of Anxiety Scores by HADS and SAS Scales Between CRT Group and Control Group Two scales for anxiety assessments were performed including HADS and SAS. No difference in HADS anxiety score at baseline, month 3, month 6, and month12 between CRT group and control group (all P > .05; Fig 4, A). In addition, the HADS anxiety score change (M12baseline) was decreased in CRT group (¡.23 § .20)
compared to control group (.62 § .17; P = .002; Fig 4, B). As for SAS score, there was no difference in SAS score at baseline, month 3 and month 6 between 2 groups (all P > .05), while SAS score was lower in CRT group than that in control group (P < .05; Fig 4, C). In addition, the SAS score change (M12-baseline) was decreased in CRT group (¡.23 § .20) compared to control group (2.00 § .77; P = .006; Fig 4, D). Furthermore, analysis of anxiety grade after treatment was assessed (Fig 5; Supplementary Table S3.). No difference was found in the occurrence rate of anxiety assessed by HADS-anxiety between 2 groups (Fig 5, A), while lower occurrence rate of anxiety assessed by SAS was observed in CRT group compared to control group (P = .033; Fig 5, B). As to grade, no difference in the number of patients with light,
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Figure 2. Comparison of MOCA score between CRT group and control group. No difference in MOCA score at baseline and month 3 between groups, while the mean value of MOCA score in CRT group was higher than that in control group at month 6 and month 12 (A). The MOCA score change (M12-baseline) was higher in CRT group compared to control group (B). No difference was found in the percentage of cognitive impairment by MOCA score 26 at baseline between 2 groups, while it was lower at month 12 in CRT group compared to control group (C). Data were presented as mean § SD. Comparisons of MOCA score at each visit and the MOCA score change (M12-baseline) were determined by t test (error bars presented as SD). Comparison of the percentage of cognitive impairment by MOCA score 26 was determined by chi-square test. *P < .05, **P < .01, ***P < .001, NS means no significance. Abbreviations: CRT, comprehensive rehabilitation training; MOCA, montreal cognitive assessment; SD, standard deviation.
moderate, and severe HADS-anxiety grade (Fig 5, C) and SAS grade (Fig 5, D) between 2 groups was observed (all P > .05).
Comparison of Depression Scores by HADS and SDS Scales Between CRT Group and Control Group Two scales for depression assessments were performed including HADS and SDS. As shown in Figure 6, there was no difference in HADS depression score at each visit between 2 groups (all P > .05; Fig 6, A). As to HADS depression score change (M12-baseline), it was decreased in CRT group (¡.71 § .23) compared to control group (.44 § .18; P < .001; Fig 6, B). As to SDS score, no difference in SDS score between CRT group and control group at baseline, month 3 and month 6 (P > .05), while it was lower at month 12 in CRT group compared to control group (P < .05; Fig 6, C). The SDS score change (M12-baseline) was decreased in CRT group (¡2.10 § 1.10) compared to control group (2.30 § .88; P = .002; Fig 6, D).
Furthermore, there was no difference in the occurrence rate of depression assessed by HADS-depression between CRT and control groups (Fig 7, A), while decreased occurrence rate of depression assessed by SDS was found in CRT group compared to control group (P = .022; Fig 7, B; Supplementary Table S4). As to grade, no difference in the number of patients with light, moderate, and severe HADS-depression grade (Fig 7, C) and SDS grade (Fig 7, D) between 2 groups was observed (all P > .05).
Discussion In the current study, we observed that (1) CRT decreased cognitive impairment assessed by MOCA score and MMSE score; (2) CRT reduced anxiety assessed by HADS anxiety score and SAS score; and (3) CRT contributed to the anesis of depression evaluated by HADS depression score and SDS score in poststroke patients. There was no difference in these results between ITT
Figure 3. Comparison of MMSE score between CRT group and control group. No difference in MMSE score at each visit was found between groups (A). The MMSE score change (M12-baseline) was higher in CRT group than that in control group (B). No difference was observed in the percentage of cognitive impairment by MMSE score 26 at baseline and month 12 between groups (C). Data were presented as mean § SD. Comparisons of MMSE score at each visit and the MMSE score change (M12-baseline) were determined by t test (error bars presented as SD). Comparison of the percentage of cognitive impairment by MMSE score 26 was determined by chi-square test. *P < .05, **P < .01, ***P < .001, NS means no significance. Abbreviations: CRT, comprehensive rehabilitation training; MMSE, minimum mental state examination; SD, standard deviation.
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Figure 4. Comparison of HADS anxiety score and SAS score between CRT group and control group. No difference in HADS anxiety score at each visit between groups (A). The HADS anxiety score change (M12-baseline) was decreased in CRT group compared to control group (B). No difference was observed in SAS score at baseline, month 3 and month 6 between 2 groups, while SAS score was lower in CRT group than that in control group at month 12 (C). The SAS score change (M12-baseline) was decreased in CRT group compared to control group (D). Data were presented as mean § SD and difference was determined by t test (error bars presented as SD). *P < .05, **P < .01, ***P < .001, NS means no significance. Abbreviations: CRT, comprehensive rehabilitation training; HASD, hospital anxiety and depression scale; SD, standard deviation.
Figure 5. Comparison of anxiety scores by HADS and SAS scales between CRT group and control group No difference was found in the occurrence rate of anxiety assessed by HADS-anxiety between 2 groups (A), while lower occurrence rate of anxiety assessed by SAS was observed in CRT group compared to control group (B). No difference in the number of patients with light, moderate and severe HADS-anxiety grade (C) and SAS grade (D) between 2 groups was observed. Comparison was performed by chi-square test or Wilcoxon rank sum test. P < .05 was considered significant. Abbreviations: CRT, comprehensive rehabilitation training; HASD, hospital anxiety and depression scale; SAS, Zung self-rating anxiety scale.
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Figure 6. Comparison of HADS depression score between CRT group and control group. No difference was found in HADS Depression score at each visit between 2 groups (A). The HADS Depression score change (M12-baseline) was decreased in CRT group compared to control group (B). No difference in SDS score between groups at baseline, month 3 and month 6, while it was lower at month 12 in CRT group compared to control group (C). The SDS score change (M12-baseline) was decreased in CRT group compared to control group (D). Data were presented as mean § SD and difference was determined by t test (error bars presented as SD). *P < .05, **P < .01, ***P < .001, NS means no significance. Abbreviations: CRT, comprehensive rehabilitation training; HASD, hospital anxiety and depression scale; SD, standard deviation; SDS, Zung self-rating depression scale.
Figure 7. Comparison of depression scores by HADS and SDS scales between CRT group and control group. There was no difference in the occurrence rate of depression assessed by HADS-depression between CRT and control groups (A), while decreased occurrence rate of depression assessed by SDS was found in CRT group compared to control group (B). No difference in the number of patients with light, moderate and severe HADS-depression grade (C) and SDS grade (D) between 2 groups was observed. Comparison was performed by chi-square test or Wilcoxon rank sum test. P < 0.05 was considered significant. Abbreviations: CRT, comprehensive rehabilitation training; HASD, hospital anxiety and depression scale; SDS, Zung self-rating depression scale.
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analysis and per-protocol analysis in this randomized controlled study. Effective rehabilitation interventions which are early initiated, promote the recovery effectiveness and minimize functional disability in poststroke patients.14 Accumulating evidence have proven that stroke rehabilitation plays an important role in the improvement of motor function in patients with subacute stroke, a first episode of ischemic stroke, spastic quadriplegia, and neuropsychiatric systemic lupus erythematosus.15-18 As for sensory function, including cognitive impairment that is one of common sequelae after stroke, one previous study discloses that after regular rehabilitation, both of MMSE and MOCA score are increased apparently, which are better than that in control group, suggesting that stroke rehabilitation obviously improve the cognitive function in poststroke patients.19 Another study indicates that computerbased cognitive rehabilitation program contributes toward the recovery of cognitive function and visual perception in acute stroke patients.20 Although these previous studies identify that some stroke rehabilitations obviously improve the cognitive function in poststroke patients, limited information about the role of CRT in cognitive impairment after stroke. In the present study, we designed a novel CRT programme, a complex rehabilitation program being individualized according to the initial evolutionary stage, motor impairment, and psychiatric disorders, and we applied MMSE and MOCA as evaluation tools and we observed that CRT contributed to the anesis of cognitive impairment in poststroke patients. The possible reasons were as follows: (1) CRT, consisting of patient and family member education, cognitive training, rehabilitation training as well as regular check, is a complex rehabilitation program to comprehensively train motor and sensory function, thereby promoting stroke rehabilitation and decreasing cognitive impairment. (2) CRT is a cyclical process involving: assessment, goal setting, intervention, and reassessment, which could increase the awareness of patients, caregivers, and nurses to clearly know the state of illness and intimately observe the illness changes, thereby minimising stroke complications and reducing cognitive impairment in poststroke patients. After a stroke, much of patients suffer motor and sensory impairments, which limit their mobility, self-care ability, and social participation, thereby making them losing their confidence, increasing risk of anxiety, and depression.21 There are several previous studies, which have proven the positive effects of stroke rehabilitation on motor function after stroke, while few studies have been performed related to the role of CRT, which is a comprehensive rehabilitation program involving in motor training, sensory training as well as regular psychological assessment, in the anxiety and depression of poststroke patients.7,16,17 Hence, in the present study, we designed CRT and investigated the effects of CRT on anxiety and depression assessed by HADS score and SAS/SDS score
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in poststroke patients, and we found that CRT could decrease anxiety and depression in poststroke patients. The possible reasons were that (1) CRT contributes to the recovery of motor and sensory impairments, and its longterm improvement of ADL ability provide patients with new hope, thereby increasing their confidence and decreasing anxiety as well as depression in poststroke patients. (2) CRT, which is a training completed by patients with assistance of caregivers and nurses, increases communication time among them, maintaining a good environment with more understanding and cooperation, thereby promoting the regulation of mental health and reducing the anxiety as well as depression in poststroke patients. There were still some limitations in this study. First, the follow-up duration was relatively short, it was 12 months in this study, which did not investigate the long-term effects of CRT on cognitive impairment, anxiety, and depression in poststroke patients. Second, the sample size in this study was relatively small, which only enrolled 84 patients in CRT group and 84 patients in control group, thus, the statistics power might be low. Third, this study was a single institutional study, and all patients were from monocentric, thus, further study with more patients from multicenter is necessary. In conclusion, CRT contributes to the recovery of cognitive impairment, and decreases anxiety and depression in poststroke patients. Conflict of Interest: conflict of interest.
The authors declare that they have no
Supplementary Materials Supplementary data to this article can be found online at doi:10.1016/j.jstrokecerebrovasdis.2018.05.038.
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