Acta Neurol Scand 2016: 133: 30–40 DOI: 10.1111/ane.12420
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA
Cognitive rehabilitation in multiple sclerosis: a randomized controlled trial Hanssen KT, Beiske AG, Landrø NI, Hofoss D, Hessen E. Cognitive rehabilitation in multiple sclerosis: a randomized controlled trial. Acta Neurol Scand 2016: 133: 30–40. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
K. T. Hanssen1,2, A. G. Beiske1, N. I. Landrø3, D. Hofoss4, E. Hessen2,3,5 1
Multiple Sclerosis Centre Hakadal, Oslo, Norway; Department of Neurology, Akershus University Hospital, Oslo, Norway; 3Clinical Neuroscience Research Group, Department of Psychology, University of Oslo, Oslo, Norway; 4Institute of Health and Society, University of Oslo, Oslo, Norway; 5Department for Complex Epilepsy, Oslo University Hospital, Oslo, Norway 2
Background – The evidence base in cognitive rehabilitation in multiple sclerosis (MS) is still sparse. Objective – The aim of the study was to investigate the effects of cognitive rehabilitation on cognitive and executive coping, psychological well-being and psychological aspects of health-related quality of life (HRQoL) in patients with MS. Methods – One hundred and twenty patients with cognitive complaints, taking part in a 4-week multidisciplinary rehabilitation, were randomized to an intervention group (n = 60) and a control group (n = 60). Both groups underwent neuropsychological assessment with subsequent feedback and took part in general multidisciplinary MS rehabilitation. Additionally, the intervention group participated in cognitive group sessions as well as individual sessions. The main focus was to formulate Goal Attainment Scaling goals for coping with cognitive challenges. For 3 months past rehabilitation, the intervention group received biweekly telephone follow-up, focusing on goal attainment. Results – Executive functioning improved significantly from baseline to four and 7 months in both groups. Improvements in psychological well-being and psychological aspects of HRQoL occurred only in the intervention group. Conclusion – Multicomponent cognitive rehabilitation administered within the context of multidisciplinary rehabilitation can improve psychological well-being and psychological aspects of HRQoL.
Introduction
Cognitive symptoms affect up to 60% of patients with multiple sclerosis (MS) and have been described as potentially the most disabling symptoms of the disease (1). MS patients’ intelligence, basic attention, and essential verbal skills are usually intact (2), but problems related to executive functioning, complex attention, learning, memory, and information processing speed are common (3). Cognitive MS symptoms can negatively interfere with quality of life (QoL) (4, 5), daily functioning, independence (6), employment status, and participation in social activities (7–9) and have along with psychiatric symptoms been shown to significantly contribute to caregiver distress (10). Due to the high prevalence and possible detrimental consequences of cognitive 30
Key words: multiple sclerosis; rehabilitation; quality of life; neuropsychology K. T. Hanssen, Multiple Sclerosis Centre, Blomsterbakken 33, 1487 Hakadal, Oslo, Norway Tel.: (+47) 67062900 Fax: (+47) 67076395 e-mail: [email protected] Accepted for publication April 10, 2015
symptoms, it has been claimed that alleviation of these symptoms should be a major goal of MS research and practice (3). The prevalence of mood disorders in MS is high, both compared with the general population and with populations with comparable degrees of physical disability (5). Depression is the most common comorbid psychiatric condition (11) and contributes significantly to executive and cognitive problems (5, 12). The lifetime risk of depression is 50% (5, 13), compared with a probability in the general population of 10–15% (14). Poorer health-related quality of life (HRQoL) has been reported among patients with MS than in the general population (15) and in other groups of chronic diseases (16). As no curative pharmacological treatment of MS (2) or cognitive MS symptoms (17) currently is recommended, efforts aimed at alleviating
Cognitive MS rehabilitation cognitive and psychological problems of daily functioning, psychological well-being, and HRQoL are highly relevant. It has been suggested (18) that outcome measures in cognitive MS rehabilitation should focus on whether the rehabilitation reaches the aims of (i) helping the patient to function to the maximum level possible within the constraints of the disease and (ii) helping the patient and the relatives to be as content and satisfied with the condition as possible. It has been emphasized (18) that cognitive rehabilitation is expected to improve mood and claimed that improvement in QoL should be the ultimate goal of cognitive rehabilitation. Several reviews have concluded that there still is a lack of high-quality studies on cognitive MS rehabilitation (3, 5, 7, 19). A recent meta-analysis of randomized and quasi-randomized trials indicated that cognitive training can improve memory span and working memory (20). It further indicated that cognitive training combined with other neuropsychological methods can improve attention, immediate verbal memory, and delayed memory. A general positive effect on emotional functions or QoL was not indicated (20). However, when individually analyzed, several studies showed positive effects of neuropsychological rehabilitation on depression (17, 21, 22). Due to the individual needs and often complex challenges related to cognitive symptoms, a multicomponent, multidisciplinary approach to cognitive MS rehabilitation has been recommended (23–26). As cognitive rehabilitation typically is a mix of various components tailored to the individual’s needs, the relative effects from the different parts of the intervention can be difficult to separate. Rosti-Otajarvi et al. (27) underlined the particular challenge of separating intervention effects from placebo effects in cognitive rehabilitation studies using subjective outcome measures. They recommended using a low-intensity intervention group as comparator. In line with this, the control group in this study participated in ordinary multidisciplinary rehabilitation at the same rehabilitation center where the cognitive intervention was administered. To improve coping with cognitive and executive problems, psychological well-being and HRQoL, we applied a multicomponent cognitive rehabilitation program for patients with MS. The program started with 4 weeks of multidisciplinary inpatient rehabilitation. It included neuropsychological assessment with feedback, participation in cognitive group sessions, guidance through the
process of formulating Goal Attainment Scaling goals (GAS goals) (32) for coping with cognitive problems and biweekly telephone follow-up the three-first months after the inpatient rehabilitation stay, focusing on goal attainment. The GAS method is suitable for measuring ongoing, individualized goal attainment in real-world and has successfully been employed in a variety of clinical practice and research, such as community mental health, TBI, MS, and other conditions (31, 32, 52). The primary goal of the intervention was to increase awareness of cognitive strengths and problems with a specific focus on executive functioning and to increase cognitive coping in everyday life. Additionally, the intervention aimed at improving psychological well-being and HRQoL. The main hypotheses were that the program would lead to improvement in: 1. Self-reported executive functioning, 2. Psychological well-being, and 3. Psychological aspects of HRQoL.
Methods
The study followed a prospective, randomized controlled design. Concealment of treatment allocation was not possible due to the nature of the intervention. The study was approved by the Regional Committee for Medical Research Ethics, and the participants provided written informed consent to participate. Sample size
The sample size was decided from Altman’s nomogram (28) (p.456). We wanted to include sufficient patients to be able to document a standardized effect of 0.5. We accepted a maximum risk of type 1 errors on 5% and a maximum risk of type 2 errors on 20% (i.e. a test power of 0.8). Consequently, we needed to include 120 patients in the study, 60 in the intervention group, and 60 in the control group. Patients
The study population consisted of participants at multidisciplinary, inpatient rehabilitation programs of 4 weeks duration, offered exclusively for patients with MS. Inclusion was based on the following criteria: 1. Subjective complaints about cognitive problems. This information was collected in structured and standardized individual interviews 31
Hanssen et al.
2. 3.
4. 5.
6.
where each participant was asked to describe his or her cognitive complaints. Motivation for working with cognitive problems to increase coping in everyday life. Adequate language skills to participate in group discussions without any need for an interpreter. None of the patients were excluded based on this criterion. No central nervous system injury or disease other than MS. No psychopathology that would negatively interfere with participation in the cognitive rehabilitation. No general cognitive impairment defined as a scores from 24 and below on the Mini Mental State Examination (MMSE) (29, 30). No patients were excluded based on this criterion.
Figure 1 shows the patient flow from inclusion, randomization, intervention, and finally registration of primary outcome measures, 7 months past randomization. The 120 participants included in the study were randomized to take part in either the intervention group or the control group. One participant in the intervention group decided to withdraw prior to the intervention. All 120 underwent neurological examination; however, three were not assessed with the Expanded Disability Status Scale (EDSS): one in the intervention group and two in the control group, due to temporary lack of qualified personnel, 115 underwent neuropsychological assessment: 56 in the intervention group and 59 in the control group. Two patients in the intervention group dropped out prior to completing the neuropsychological assessment. Two patients in the intervention group had recently gone through similar neuropsychological assessment, and scores from those assessments were obtained to serve as basis for cognitive rehabilitation. One patient in the control group refused neuropsychological assessment. The patients in both groups were asked to complete the primary outcome questionnaires at baseline, after 4 weeks, and four and 7 months past the start of the rehabilitation. The patients in the intervention group were guided through the process of formulating Goal Attainment Scaling (GAS) (31, 32) goals for coping with cognitive problems in everyday life. GAS is a method for quantifying the attainment of individualized goals set in rehabilitation. In the GAS procedure, five different levels of outcomes are operationalized and given a numeric value, where 2 represents goal attainment much worse than expected, 1: a little worse than expected, 0: as expected, +1: somewhat better 32
than expected, and +2: much better than expected. The patient can establish as many or few goals as he/she desires, and outcomes can be summed within different patient goals as well as across patients to assess overall outcomes of treatment programs (31). Fifty-seven patients completed the GAS goal formulation and complied with the 3-month biweekly telephone follow-up. At 7 months past the start of the intervention, we were able to reach 53 of the patients for a telephone administered follow-up session that also included scoring of GAS goal attainment. Randomization
Information about the cognitive rehabilitation intervention and the study was given in a brief lecture at the beginning of the rehabilitation stay. Volunteers were interviewed individually about cognitive problems and motivation for participation. Randomization was performed by a lottery controlled by the director of the rehabilitation center. Those randomized to the intervention group received cognitive rehabilitation, in addition to the ordinary rehabilitation program offered by the center. The participants in the control group were offered neuropsychological assessment, including feedback, and otherwise participated in the ordinary 4-week rehabilitation program of individual follow-up by a multidisciplinary team: neurologist, physiotherapist, social worker, occupational therapist, and nursing staff. Physical activities and lectures about MS-related topics were offered daily. As part of the ordinary rehabilitation program, participants in the control group had the opportunity to consult a clinical psychologist and attend lectures on cognitive and psychological aspects of MS. After the study period, participants in the control group who returned for subsequent rehabilitation stays were prioritized for participation in the cognitive rehabilitation program, if they wanted to. The cognitive intervention
During the first week, the participants in the intervention group underwent neuropsychological assessment followed by a feedback session. To facilitate metacognitive awareness, cognitive strengths and symptoms were discussed with the patient and related to everyday challenges. Cognitive strengths and symptoms were summarized in a form called: ‘My Cognitive Rehabilitation
Cognitive MS rehabilitation Participants at 4 week-long in-patient rehabilitation at Multiple Sclerosis Centre Hakadal Nov. 2010 – Aug. 2012 Volunteers meeting the inclusion criteria (n = 120) Randomization
Intervention group (I) (n = 60)
Dropout (n = 1) Decided to with-draw from study prior to the intervention
Control group (C) (n = 60)
Completing questionnaires at baseline (n = 120) Neurological examination (n = 120) Included EDSS (n = 117) (I = 59, C = 58) Neuropsychological examination (n = 115) (I = 56, C = 59) I: 2 recently assessed, not re-assessed in study C: 1 refused
I: Completed standard 4 week inpatient rehab. program (n = 59) + 3 cognitive group sessions and 5 individual cognitive rehab. sessions (n = 57) Dropout (n = 2) -Left rehab. due to illness in family (n = 1) -Decided to withdraw from study (n = 1)
C: Completed standard 4 week inpatient rehab. program (n = 59)
Completing primary outcome measures before departure from rehab. center (n = 113) (I = 57, C = 56)
Dropout (n = 1) -Left rehab. due to illness other than MS
I: 6 biweekly telephone follow-up calls over three months past inpatient rehab. (n = 57)
Completing primary outcome measures, 4 months past start of rehab. (n = 103) (I = 51, C = 51)
I: Scoring of goal attainment 7 months past start of rehab. (n = 53)
Completing primary outcome measures, 7 months past start of rehab. (n = 101) (I = 54, C = 48)
Figure 1. Patient flowchart.
Goals’ which was given to the patient. The form contained a section providing general advice for coping with cognitive problems and sections in which the patient could enter goals and operationalize behaviors required to reach them. The form was continually updated by the patient, under supervision of the neuropsychologist and the occupational therapist, as the goal setting proceeded during the rehabilitation stay. Before discharge, the most important goals were converted into GAS goals (32). During the rehabilitation stay, the patients in the intervention group took part in three cognitive group sessions, each of 2 h duration, aiming to increase their awareness of their cognitive
strengths, problems, and coping strategies. The groups consisted of three to six patients, and sessions were conducted by the study neuropsychologist and the study occupational therapist. The sessions included lectures, practical exercises, and discussions. The main theme of the first session was cognitive functions and principles of goal setting. The second session included a lecture about executive functions, a group exercise related to planning, and a discussion of strategies for keeping track of appointments and belongings. The third session dealt with how cognitive symptoms can affect communication, how to cope with such challenges, and how to communicate about MS. 33
Hanssen et al. During the second and third week of the rehabilitation stay, the patients in the intervention group took part in individual sessions, one with a neuropsychologist and one with an occupational therapist. To support the goal setting process, techniques from Motivational Interviewing (33) and cognitive behavioral therapy were utilized. The first 3 months after discharge from the rehabilitation center, the patients in the intervention group took part in a total of six biweekly telephone sessions focusing on attainment of the individual GAS goals set during the rehabilitation stay. In all, participants and therapists in the intervention group were together for approximately 4 h of neuropsychological assessment with feedback, 5 h of individual sessions, 6 h of cognitive group sessions, one lecture about MS, and cognition in addition to the six telephone calls of approximately 10 min each, administered past discharge from the rehabilitation center. The number and timing of individual sessions were similar for all the participants in the intervention group. The different components in the intervention are summarized in Table 1. Neuropsychological assessment
Baseline neuropsychological assessment included the following frequently used and well-validated instruments: 1. General cognitive ability: Wechsler Abbreviated Scale of Intelligence (WASI) (34) 2. Verbal learning and memory: Hopkins Verbal Learning Test (HVLT) (35) and Logical Memory, Wechsler Memory Scale—Revised (WMSR) (36) 3. Visual memory: Rey Complex Figure Test and Recognition Trial (37) 4. Working memory: Digit Span, Wechsler Adult Intelligence Scale-III (38) and Spatial Span, Wechsler Memory Scale-III (39) 5. Executive functions: Trail Making Test B (40), Controlled Oral Word Association Test (41),
and Tower Test and Stroop Test, D-KEFS (42) 6. Information processing speed: Symbol Digit Modality Test (43), Digit-symbol Test, WAISIII (38), and Trail Making Test A (40) 7. Motor speed and coordination: Grooved Pegboard test (44)
Questionnaires
1. Executive functions were assessed by the Norwegian version of Behavior Rating Inventory of Executive Function for adults (BRIEF-A) (45). BRIEF-A raw scores were converted to T-scores, a normally distributed scale with a mean score of 50 and standard deviation (SD) of 10. Higher scores on BRIEF-A indicate higher levels of executive complaints. 2. Psychological health was assessed by Hopkins Symptom Checklist-25 (HSCL-25) (46), a screening instrument measuring symptoms of anxiety (item 1–10) and depression (item 11– 25), validated in Norwegian (47). Each item was scored on a scale from 1 (not bothered) to 4 (extremely bothered), and the total score was divided by 25, resulting in a total score for the HSCL-25 ranging between 1 and 4, higher scores indicating a higher symptom load. 3. Health-related quality of life (HRQoL) was measured by Multiple Sclerosis Impact Scale (48) and Norwegian version (MSIS-29 NV) (49). MSIS-29 is a self-report scale focusing on the impact of MS on physical and psychological health. In line with the aims of the intervention, only the psychological subscale of MSIS-29 was included in the analysis. This scale ranges from nien to 45, higher scores indicating poorer HRQoL.
Data collection
Both the intervention group and the control group responded to the questionnaires when they
Table 1 Components of the cognitive rehabilitation program
Week 1 NP assessment
Individual feedback session with NP and OT (provided during week 1 or 2)
Week 2 Cognitive group session 1 MS, cognition, and goal setting Individual session with NP Individual session with OT
Week 4
Three first months past discharge from rehabilitation center
Cognitive group session 2 Executive functions
Cognitive group session 3 Communication
Biweekly telephone follow-up calls Scoring of GAS goal attainment
Individual session with NP Individual session with OT
Individual session with NP and OT Defining individual GAS goals
Week 3
NP assessment, Neuropsychological assessment; NP, Neuropsychologist; OT, Occupational therapist.
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Cognitive MS rehabilitation entered the rehabilitation, at discharge from the 4-week inpatient program and then at four and 7 months past start of the rehabilitation. For the intervention group, individual goal attainment was scored during the biweekly follow-up calls during the first 3 months past the inpatient program, and finally at 7 months past the start of the intervention, each time by the GAS method as described by Malec (31). Statistical analysis
The primary outcomes were changes in selfreported executive functioning, psychological well-being and psychological aspects of HRQoL. Statistical analyses were performed with the Statistical Package for Social Sciences for Windows (SPSS, version 20.0). First, descriptive statistics of the demographic and clinical characteristics of the control and intervention group were computed. Group differences were tested by independent samples t-test and chi-square tests. Secondly, neuropsychological characteristics of the study population were computed. Paired sample statistics were used to compare the scores for the primary outcome measures within the intervention and the control groups from baseline to four and 7 months after the start of the rehabilitation. Then, independent t-tests were performed comparing differences in change for the primary outcomes between the control group and the intervention group from baseline to four and 7 months after start of intervention. Results
(SD = 8.9) obtained in a large study based on the United Kingdom MS Register (50). The HSCL25 Total is a measure of symptoms typical for anxiety and depression. The intervention group had a mean score of 1.76 (SD = 0.54) and the mean score for the control group was 1.77 (SD = 0.44). These scores are approximately 2 SD above the mean scores of 1.18 (SD = 0.25) for persons with no mental disorder in a large Swedish population based study (51) and about 0,5 SD above the mean score of 1.53 (SD = 0.50) for persons with a clinical diagnosis. Neuropsychological characteristics
Neuropsychological characteristics of the study population are presented in Table 3. On group level the study population achieved T-scores within normal range on most of the neuropsychological tests. However, results on several tests that require motor and psychomotor speed (Grooved Pegboard, SDMT, Digit Symbol and TMT A+B) were poorer, ranging from 0.9 to 1.5 SD below the normative mean. Both the control group, that took part in 4week ordinary inpatient MS rehabilitation, and the intervention group, that additionally received a 4 month cognitive intervention program, improved significantly from baseline to four and 7 months after start of the rehabilitation on the Global Executive Composite Score and the Metacognitive Index from the BRIEF-A. However, only the intervention group showed significant Table 2 Baseline characteristics of patients
Demographical and clinical characteristics
There were no significant baseline differences between the intervention group and the control group regarding age, education, gender, work, sick leave/disability benefit, marriage, number of years since diagnosis, EDSS, Primary Progressive MS, Relapsing Remitting MS, Secondary Progressive MS, Intelligence Quotient Global Executive Composite Score (BRIEF-A), Metacognitive Index (BRIEF-A), or MSIS-29 Psychological Scale or HSCL-25 total score (Table 2). The mean scores on the executive subscales from the BRIEF-A inventory were approximately 1 SD above the normative mean for both the intervention group and the control group. On the psychological subscale of the MSIS-29, the group mean for the intervention group was 21.6 (SD = 7.7), and 21.4 (SD = 6.9) for the control group, both somewhat lower than the mean score of 24.8
Control group (n = 60) Mean age (range) Years of education (range) Female (%) Work (%) Sick leave/disability benefit (%) Married/living with a partner (%) Years since diagnosis (SD) EDSS (SD) Primary Progressive MS (%) Relapsing Remitting MS (%) Secondary Progressive MS (%) IQ (SD) GEC (BRIEF-A), T-score (SD) MI (BRIEF-A), T-score (SD) MSIS-29 Psychological scale (SD) HSCL-25 total score (SD)
52.5 13.5 48 7 53 46 12.0 4.2 10 32 18 111.8 60.9 61.8 21.4 1.77
(32–71) (8–18) (80.0) (11.7) (88.3) (76.7) (9.7) (1.7) (16.7) (53.3) (30.0) (10.7) (11.5) (11.6) (6.9) (0.44)
Intervention group (n = 60) 53.9 13.1 40 6 54 44 10.6 4.4 18 27 15 111.8 60.7 62.3 21.6 1.76
(33–70) (9–18) (66.7) (10.0) (90.0) (73.3) (7.7) (1.7) (30.0) (45.0) (25.0) (12.5) (11.1) (11.3) (7.7) (0.54)
P-values n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s.
EDSS, Expanded Disability Status Scale; GEC (BRIEF-A), General Executive Composite from the Behavior Rating Inventory of Executive Function; MI, Metacognition Index; MSIS-29, Multiple Sclerosis Impact Scale-29; HSCL-25, Hopkins Symptoms Checklist-25.
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Hanssen et al. improvement after four and 7 months on the MSIS-29 Psychological Scale and the HSCL-25 total score (Table 4). Differences in change, between the control group and the intervention group, after four and Table 3 Neuropsychological characteristics of the study population Mean T-scores (SD) if not otherwise specified
Test (n) WASI Verbal IQ (114) WASI Performance IQ (115) WASI Full scale IQ (112) WAIS Digit span (115) WMS-III Spatial span (115) SDMT Written (105) SDMT Oral (105) WAIS Symbol digit (110) TMT-A (113) TMT-B (114) D-KEFS Stroop CW (112) D-KEFS Stroop CW/Switching (112) Logical Memory, Immediate Recall (115) Logical Memory Delayed Recall (115) HVLT Total Recall (115) HVLT-R Delayed Recall (115) HVLT-R Retention (%) (112) RCFT Delayed Recall (113) RCFT Recognition Trial (111) D-KEFS Tower Test (107) Peg Board Dominant Hand (110) Peg Board Non-dominant Hand (108) COWAT Letters (115) COWAT Animals (114)
111 110 112 43 50 38 42 40 41 41 48 45 55 55 47 48 49 47 46 54 36 35 45 50
(11.1) (12.4) (11.6) (6.8) (9.2) (14.1) (13.5) (9.9) (13.9) (13.8) (11.5) (12.2) (8.9) (8.6) (11.2) (11.9) (11.7) (14.3) (11.1) (7.5) (15.7) (13.9) (10.3) (14.1)
WASI, Wechsler Abbreviated Scale of Intelligence; WMS, Wechsler Memory Scale; SDMT, Symbol Digit Modalities Test; WAIS, Wechsler Adult Intelligence Scale; TMT, Trail Making Test; D-KEFS, Delis–Kaplan Executive Function System; HVLT-R, Hopkins Verbal Learning Test Revised; RCFT, Rey Complex Figure Test and Recognition Trial; COWAT, Controlled Oral Word Association Test. Table 4 Change from baseline to four and 7 months for the control group and the intervention group
Control group GEC (BRIEF-A), T-score (SD) MI (BRIEF-A), T-score (SD) MSIS-29 Psychological scale (SD) HSCL-25 total score (SD)
Intervention group GEC (BRIEF-A), T-score (SD) MI (BRIEF-A), T-score (SD) MSIS-29 Psychological Subscale (SD) HSCL-25 total score (SD)
Baseline N = 60
Four months N = 51
Seven months N = 48
60.0 (10.6) 61.0 (10.5) 20.9 (6.6)
56.7 (11.7)** 57.8 (10.7)** 19.9 (7.7) n.s.
55.2 (11.5)** 56.7 (10.9)** 20.6 (8.0) n.s.
1.75 (0.42)
1.74 (0.50) n.s.
1.65 (0.53) n.s.
Baseline N = 60
Four months N = 51
Seven months N = 54
61.1 (11.0) 62.7 (11.3) 21.3 (7.0)
56.4 (11.7)** 58.2 (11.8)** 18.3 (6.9)**
56.3 (11.8)** 57.7 (11.9)** 18.3 (7.2)**
1.76 (0.53)
1.60 (0.49)*
1.62 (0.47)**
BRIEF-A, Behavior Rating Inventory of Executive Function – Adult version; GEC, General Executive Composite; MI, Metacognition Index; HSCL-25, Hopkins Symptom Checklist- 25; MSIS-29, Multiple Sclerosis Impact Scale-29. *P < 0.05 **P < 0.01.
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7 months on the outcome variables, are shown in Table 5. Both groups improved significantly on the executive variables at the two measurement points, and there were no significant differences in change between the groups on these variables. However, on the scale measuring psychological aspects of HRQoL (MSIS-29), the intervention group improved close to significantly (P = 0.06) more than the control group after 4 months and significantly more than the control group after 7 months (P = 0.03). Similar results were found for the HSCL-25, primarily measuring symptoms of anxiety and depression: the intervention group improved significantly more after 4 months (P = 0.05). The HSCL-25 score improved after 7 months as well, however, not significantly. Discussion
The current RCT investigated the effects of a multicomponent cognitive rehabilitation program aiming to improve cognitive and executive coping, psychological well-being and psychological aspects of HRQoL in MS patients with cognitive complaints. The main findings were that: 1. Self-reported executive functioning improved significantly from baseline to four and 7 months both in the intervention group and in the control group, whereas significant improvement in psychological well-being and psychological aspects of HRQoL occurred only in the intervention group. 2. The intervention group showed significantly or nearly significantly larger improvements than the control group in psychological aspects of HRQoL at four and 7 months after the start of the rehabilitation program, as well as significant improvement in psychological well-being after 4 months. The main difference between the cognitive rehabilitation program and the general multidisciplinary rehabilitation program in the current study was the guidance through the process of formulating and implementing individual GAS goals for coping with cognitive challenges in everyday life. Consistent with previous studies, we found that GAS was a feasible outcome measure in MS rehabilitation (52) and that the GAS goals set by the participants in the intervention group were well achieved and maintained throughout the study period (53–55). A strength of the current study was the utilization of a randomized controlled design. The sample size (n = 120) was large enough to ensure
Cognitive MS rehabilitation Table 5 Differences in change between the control group and the intervention group from baseline to four and 7 months after start of intervention Control group Variables
N
GEC (BRIEF-A), T-score (SD) MI (BRIEF-A), T-score (SD) MSIS-29 Psych. scale, raw score (SD) HSCL-25 Total score, raw score (SD)
60 60 59 60
Changes after 7 months GEC (BRIEF-A), T-score (SD) MI (BRIEF-A), T-score (SD) MSIS-29 Psych. scale, raw score (SD) HSCL-25 Total score, raw score (SD)
Baseline 60.9 61.8 21.4 1.8
(11.5) (11.6) (7.0) (0.4)
Baseline 60 60 59 60
60.9 61.8 21.4 1.8
(11.5) (11.6) (7.0) (0.42)
Intervention group
4 months
N
N
56.8 57.8 20.0 1.74
51 51 50 51
59 59 60 59
(11.7) (10.7) (7.7) (0.5)
7 months 55.2 56.7 20.5 1.7
(11.5) (10.9) (8.0) (0.5)
sufficient statistical power to reveal differences between the groups. The intervention group and the control group were similar at baseline, and the dropout rate was acceptable. The participants underwent comprehensive neuropsychological assessment with well-validated instruments. Additionally, methodologically sound instruments were used for collection of data on goal attainment and primary outcomes. The timing of individual sessions, group sessions, and outcome assessment was identical for all the patients. The possibility of placebo effects cannot be ruled out completely. Due to the nature of the intervention, blinding of treatment allocation was not possible, and participants were aware of their group affiliation as well as the objectives of the intervention. To reduce the risk for positive response biases, objective measurement tools were utilized and the participants were encouraged to give accurate answers. Nonetheless, the intervention group did receive an additional intervention, whereas no control or sham intervention was provided to the control group. The study population represented a selected group of highly motivated patients, recruited from a multidisciplinary inpatient rehabilitation program offered for MS patients with a low to moderate neurological symptom load, as measured by EDSS
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA
Cognitive rehabilitation in multiple sclerosis: a randomized controlled trial Hanssen KT, Beiske AG, Landrø NI, Hofoss D, Hessen E. Cognitive rehabilitation in multiple sclerosis: a randomized controlled trial. Acta Neurol Scand 2016: 133: 30–40. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
K. T. Hanssen1,2, A. G. Beiske1, N. I. Landrø3, D. Hofoss4, E. Hessen2,3,5 1
Multiple Sclerosis Centre Hakadal, Oslo, Norway; Department of Neurology, Akershus University Hospital, Oslo, Norway; 3Clinical Neuroscience Research Group, Department of Psychology, University of Oslo, Oslo, Norway; 4Institute of Health and Society, University of Oslo, Oslo, Norway; 5Department for Complex Epilepsy, Oslo University Hospital, Oslo, Norway 2
Background – The evidence base in cognitive rehabilitation in multiple sclerosis (MS) is still sparse. Objective – The aim of the study was to investigate the effects of cognitive rehabilitation on cognitive and executive coping, psychological well-being and psychological aspects of health-related quality of life (HRQoL) in patients with MS. Methods – One hundred and twenty patients with cognitive complaints, taking part in a 4-week multidisciplinary rehabilitation, were randomized to an intervention group (n = 60) and a control group (n = 60). Both groups underwent neuropsychological assessment with subsequent feedback and took part in general multidisciplinary MS rehabilitation. Additionally, the intervention group participated in cognitive group sessions as well as individual sessions. The main focus was to formulate Goal Attainment Scaling goals for coping with cognitive challenges. For 3 months past rehabilitation, the intervention group received biweekly telephone follow-up, focusing on goal attainment. Results – Executive functioning improved significantly from baseline to four and 7 months in both groups. Improvements in psychological well-being and psychological aspects of HRQoL occurred only in the intervention group. Conclusion – Multicomponent cognitive rehabilitation administered within the context of multidisciplinary rehabilitation can improve psychological well-being and psychological aspects of HRQoL.
Introduction
Cognitive symptoms affect up to 60% of patients with multiple sclerosis (MS) and have been described as potentially the most disabling symptoms of the disease (1). MS patients’ intelligence, basic attention, and essential verbal skills are usually intact (2), but problems related to executive functioning, complex attention, learning, memory, and information processing speed are common (3). Cognitive MS symptoms can negatively interfere with quality of life (QoL) (4, 5), daily functioning, independence (6), employment status, and participation in social activities (7–9) and have along with psychiatric symptoms been shown to significantly contribute to caregiver distress (10). Due to the high prevalence and possible detrimental consequences of cognitive 30
Key words: multiple sclerosis; rehabilitation; quality of life; neuropsychology K. T. Hanssen, Multiple Sclerosis Centre, Blomsterbakken 33, 1487 Hakadal, Oslo, Norway Tel.: (+47) 67062900 Fax: (+47) 67076395 e-mail: [email protected] Accepted for publication April 10, 2015
symptoms, it has been claimed that alleviation of these symptoms should be a major goal of MS research and practice (3). The prevalence of mood disorders in MS is high, both compared with the general population and with populations with comparable degrees of physical disability (5). Depression is the most common comorbid psychiatric condition (11) and contributes significantly to executive and cognitive problems (5, 12). The lifetime risk of depression is 50% (5, 13), compared with a probability in the general population of 10–15% (14). Poorer health-related quality of life (HRQoL) has been reported among patients with MS than in the general population (15) and in other groups of chronic diseases (16). As no curative pharmacological treatment of MS (2) or cognitive MS symptoms (17) currently is recommended, efforts aimed at alleviating
Cognitive MS rehabilitation cognitive and psychological problems of daily functioning, psychological well-being, and HRQoL are highly relevant. It has been suggested (18) that outcome measures in cognitive MS rehabilitation should focus on whether the rehabilitation reaches the aims of (i) helping the patient to function to the maximum level possible within the constraints of the disease and (ii) helping the patient and the relatives to be as content and satisfied with the condition as possible. It has been emphasized (18) that cognitive rehabilitation is expected to improve mood and claimed that improvement in QoL should be the ultimate goal of cognitive rehabilitation. Several reviews have concluded that there still is a lack of high-quality studies on cognitive MS rehabilitation (3, 5, 7, 19). A recent meta-analysis of randomized and quasi-randomized trials indicated that cognitive training can improve memory span and working memory (20). It further indicated that cognitive training combined with other neuropsychological methods can improve attention, immediate verbal memory, and delayed memory. A general positive effect on emotional functions or QoL was not indicated (20). However, when individually analyzed, several studies showed positive effects of neuropsychological rehabilitation on depression (17, 21, 22). Due to the individual needs and often complex challenges related to cognitive symptoms, a multicomponent, multidisciplinary approach to cognitive MS rehabilitation has been recommended (23–26). As cognitive rehabilitation typically is a mix of various components tailored to the individual’s needs, the relative effects from the different parts of the intervention can be difficult to separate. Rosti-Otajarvi et al. (27) underlined the particular challenge of separating intervention effects from placebo effects in cognitive rehabilitation studies using subjective outcome measures. They recommended using a low-intensity intervention group as comparator. In line with this, the control group in this study participated in ordinary multidisciplinary rehabilitation at the same rehabilitation center where the cognitive intervention was administered. To improve coping with cognitive and executive problems, psychological well-being and HRQoL, we applied a multicomponent cognitive rehabilitation program for patients with MS. The program started with 4 weeks of multidisciplinary inpatient rehabilitation. It included neuropsychological assessment with feedback, participation in cognitive group sessions, guidance through the
process of formulating Goal Attainment Scaling goals (GAS goals) (32) for coping with cognitive problems and biweekly telephone follow-up the three-first months after the inpatient rehabilitation stay, focusing on goal attainment. The GAS method is suitable for measuring ongoing, individualized goal attainment in real-world and has successfully been employed in a variety of clinical practice and research, such as community mental health, TBI, MS, and other conditions (31, 32, 52). The primary goal of the intervention was to increase awareness of cognitive strengths and problems with a specific focus on executive functioning and to increase cognitive coping in everyday life. Additionally, the intervention aimed at improving psychological well-being and HRQoL. The main hypotheses were that the program would lead to improvement in: 1. Self-reported executive functioning, 2. Psychological well-being, and 3. Psychological aspects of HRQoL.
Methods
The study followed a prospective, randomized controlled design. Concealment of treatment allocation was not possible due to the nature of the intervention. The study was approved by the Regional Committee for Medical Research Ethics, and the participants provided written informed consent to participate. Sample size
The sample size was decided from Altman’s nomogram (28) (p.456). We wanted to include sufficient patients to be able to document a standardized effect of 0.5. We accepted a maximum risk of type 1 errors on 5% and a maximum risk of type 2 errors on 20% (i.e. a test power of 0.8). Consequently, we needed to include 120 patients in the study, 60 in the intervention group, and 60 in the control group. Patients
The study population consisted of participants at multidisciplinary, inpatient rehabilitation programs of 4 weeks duration, offered exclusively for patients with MS. Inclusion was based on the following criteria: 1. Subjective complaints about cognitive problems. This information was collected in structured and standardized individual interviews 31
Hanssen et al.
2. 3.
4. 5.
6.
where each participant was asked to describe his or her cognitive complaints. Motivation for working with cognitive problems to increase coping in everyday life. Adequate language skills to participate in group discussions without any need for an interpreter. None of the patients were excluded based on this criterion. No central nervous system injury or disease other than MS. No psychopathology that would negatively interfere with participation in the cognitive rehabilitation. No general cognitive impairment defined as a scores from 24 and below on the Mini Mental State Examination (MMSE) (29, 30). No patients were excluded based on this criterion.
Figure 1 shows the patient flow from inclusion, randomization, intervention, and finally registration of primary outcome measures, 7 months past randomization. The 120 participants included in the study were randomized to take part in either the intervention group or the control group. One participant in the intervention group decided to withdraw prior to the intervention. All 120 underwent neurological examination; however, three were not assessed with the Expanded Disability Status Scale (EDSS): one in the intervention group and two in the control group, due to temporary lack of qualified personnel, 115 underwent neuropsychological assessment: 56 in the intervention group and 59 in the control group. Two patients in the intervention group dropped out prior to completing the neuropsychological assessment. Two patients in the intervention group had recently gone through similar neuropsychological assessment, and scores from those assessments were obtained to serve as basis for cognitive rehabilitation. One patient in the control group refused neuropsychological assessment. The patients in both groups were asked to complete the primary outcome questionnaires at baseline, after 4 weeks, and four and 7 months past the start of the rehabilitation. The patients in the intervention group were guided through the process of formulating Goal Attainment Scaling (GAS) (31, 32) goals for coping with cognitive problems in everyday life. GAS is a method for quantifying the attainment of individualized goals set in rehabilitation. In the GAS procedure, five different levels of outcomes are operationalized and given a numeric value, where 2 represents goal attainment much worse than expected, 1: a little worse than expected, 0: as expected, +1: somewhat better 32
than expected, and +2: much better than expected. The patient can establish as many or few goals as he/she desires, and outcomes can be summed within different patient goals as well as across patients to assess overall outcomes of treatment programs (31). Fifty-seven patients completed the GAS goal formulation and complied with the 3-month biweekly telephone follow-up. At 7 months past the start of the intervention, we were able to reach 53 of the patients for a telephone administered follow-up session that also included scoring of GAS goal attainment. Randomization
Information about the cognitive rehabilitation intervention and the study was given in a brief lecture at the beginning of the rehabilitation stay. Volunteers were interviewed individually about cognitive problems and motivation for participation. Randomization was performed by a lottery controlled by the director of the rehabilitation center. Those randomized to the intervention group received cognitive rehabilitation, in addition to the ordinary rehabilitation program offered by the center. The participants in the control group were offered neuropsychological assessment, including feedback, and otherwise participated in the ordinary 4-week rehabilitation program of individual follow-up by a multidisciplinary team: neurologist, physiotherapist, social worker, occupational therapist, and nursing staff. Physical activities and lectures about MS-related topics were offered daily. As part of the ordinary rehabilitation program, participants in the control group had the opportunity to consult a clinical psychologist and attend lectures on cognitive and psychological aspects of MS. After the study period, participants in the control group who returned for subsequent rehabilitation stays were prioritized for participation in the cognitive rehabilitation program, if they wanted to. The cognitive intervention
During the first week, the participants in the intervention group underwent neuropsychological assessment followed by a feedback session. To facilitate metacognitive awareness, cognitive strengths and symptoms were discussed with the patient and related to everyday challenges. Cognitive strengths and symptoms were summarized in a form called: ‘My Cognitive Rehabilitation
Cognitive MS rehabilitation Participants at 4 week-long in-patient rehabilitation at Multiple Sclerosis Centre Hakadal Nov. 2010 – Aug. 2012 Volunteers meeting the inclusion criteria (n = 120) Randomization
Intervention group (I) (n = 60)
Dropout (n = 1) Decided to with-draw from study prior to the intervention
Control group (C) (n = 60)
Completing questionnaires at baseline (n = 120) Neurological examination (n = 120) Included EDSS (n = 117) (I = 59, C = 58) Neuropsychological examination (n = 115) (I = 56, C = 59) I: 2 recently assessed, not re-assessed in study C: 1 refused
I: Completed standard 4 week inpatient rehab. program (n = 59) + 3 cognitive group sessions and 5 individual cognitive rehab. sessions (n = 57) Dropout (n = 2) -Left rehab. due to illness in family (n = 1) -Decided to withdraw from study (n = 1)
C: Completed standard 4 week inpatient rehab. program (n = 59)
Completing primary outcome measures before departure from rehab. center (n = 113) (I = 57, C = 56)
Dropout (n = 1) -Left rehab. due to illness other than MS
I: 6 biweekly telephone follow-up calls over three months past inpatient rehab. (n = 57)
Completing primary outcome measures, 4 months past start of rehab. (n = 103) (I = 51, C = 51)
I: Scoring of goal attainment 7 months past start of rehab. (n = 53)
Completing primary outcome measures, 7 months past start of rehab. (n = 101) (I = 54, C = 48)
Figure 1. Patient flowchart.
Goals’ which was given to the patient. The form contained a section providing general advice for coping with cognitive problems and sections in which the patient could enter goals and operationalize behaviors required to reach them. The form was continually updated by the patient, under supervision of the neuropsychologist and the occupational therapist, as the goal setting proceeded during the rehabilitation stay. Before discharge, the most important goals were converted into GAS goals (32). During the rehabilitation stay, the patients in the intervention group took part in three cognitive group sessions, each of 2 h duration, aiming to increase their awareness of their cognitive
strengths, problems, and coping strategies. The groups consisted of three to six patients, and sessions were conducted by the study neuropsychologist and the study occupational therapist. The sessions included lectures, practical exercises, and discussions. The main theme of the first session was cognitive functions and principles of goal setting. The second session included a lecture about executive functions, a group exercise related to planning, and a discussion of strategies for keeping track of appointments and belongings. The third session dealt with how cognitive symptoms can affect communication, how to cope with such challenges, and how to communicate about MS. 33
Hanssen et al. During the second and third week of the rehabilitation stay, the patients in the intervention group took part in individual sessions, one with a neuropsychologist and one with an occupational therapist. To support the goal setting process, techniques from Motivational Interviewing (33) and cognitive behavioral therapy were utilized. The first 3 months after discharge from the rehabilitation center, the patients in the intervention group took part in a total of six biweekly telephone sessions focusing on attainment of the individual GAS goals set during the rehabilitation stay. In all, participants and therapists in the intervention group were together for approximately 4 h of neuropsychological assessment with feedback, 5 h of individual sessions, 6 h of cognitive group sessions, one lecture about MS, and cognition in addition to the six telephone calls of approximately 10 min each, administered past discharge from the rehabilitation center. The number and timing of individual sessions were similar for all the participants in the intervention group. The different components in the intervention are summarized in Table 1. Neuropsychological assessment
Baseline neuropsychological assessment included the following frequently used and well-validated instruments: 1. General cognitive ability: Wechsler Abbreviated Scale of Intelligence (WASI) (34) 2. Verbal learning and memory: Hopkins Verbal Learning Test (HVLT) (35) and Logical Memory, Wechsler Memory Scale—Revised (WMSR) (36) 3. Visual memory: Rey Complex Figure Test and Recognition Trial (37) 4. Working memory: Digit Span, Wechsler Adult Intelligence Scale-III (38) and Spatial Span, Wechsler Memory Scale-III (39) 5. Executive functions: Trail Making Test B (40), Controlled Oral Word Association Test (41),
and Tower Test and Stroop Test, D-KEFS (42) 6. Information processing speed: Symbol Digit Modality Test (43), Digit-symbol Test, WAISIII (38), and Trail Making Test A (40) 7. Motor speed and coordination: Grooved Pegboard test (44)
Questionnaires
1. Executive functions were assessed by the Norwegian version of Behavior Rating Inventory of Executive Function for adults (BRIEF-A) (45). BRIEF-A raw scores were converted to T-scores, a normally distributed scale with a mean score of 50 and standard deviation (SD) of 10. Higher scores on BRIEF-A indicate higher levels of executive complaints. 2. Psychological health was assessed by Hopkins Symptom Checklist-25 (HSCL-25) (46), a screening instrument measuring symptoms of anxiety (item 1–10) and depression (item 11– 25), validated in Norwegian (47). Each item was scored on a scale from 1 (not bothered) to 4 (extremely bothered), and the total score was divided by 25, resulting in a total score for the HSCL-25 ranging between 1 and 4, higher scores indicating a higher symptom load. 3. Health-related quality of life (HRQoL) was measured by Multiple Sclerosis Impact Scale (48) and Norwegian version (MSIS-29 NV) (49). MSIS-29 is a self-report scale focusing on the impact of MS on physical and psychological health. In line with the aims of the intervention, only the psychological subscale of MSIS-29 was included in the analysis. This scale ranges from nien to 45, higher scores indicating poorer HRQoL.
Data collection
Both the intervention group and the control group responded to the questionnaires when they
Table 1 Components of the cognitive rehabilitation program
Week 1 NP assessment
Individual feedback session with NP and OT (provided during week 1 or 2)
Week 2 Cognitive group session 1 MS, cognition, and goal setting Individual session with NP Individual session with OT
Week 4
Three first months past discharge from rehabilitation center
Cognitive group session 2 Executive functions
Cognitive group session 3 Communication
Biweekly telephone follow-up calls Scoring of GAS goal attainment
Individual session with NP Individual session with OT
Individual session with NP and OT Defining individual GAS goals
Week 3
NP assessment, Neuropsychological assessment; NP, Neuropsychologist; OT, Occupational therapist.
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Cognitive MS rehabilitation entered the rehabilitation, at discharge from the 4-week inpatient program and then at four and 7 months past start of the rehabilitation. For the intervention group, individual goal attainment was scored during the biweekly follow-up calls during the first 3 months past the inpatient program, and finally at 7 months past the start of the intervention, each time by the GAS method as described by Malec (31). Statistical analysis
The primary outcomes were changes in selfreported executive functioning, psychological well-being and psychological aspects of HRQoL. Statistical analyses were performed with the Statistical Package for Social Sciences for Windows (SPSS, version 20.0). First, descriptive statistics of the demographic and clinical characteristics of the control and intervention group were computed. Group differences were tested by independent samples t-test and chi-square tests. Secondly, neuropsychological characteristics of the study population were computed. Paired sample statistics were used to compare the scores for the primary outcome measures within the intervention and the control groups from baseline to four and 7 months after the start of the rehabilitation. Then, independent t-tests were performed comparing differences in change for the primary outcomes between the control group and the intervention group from baseline to four and 7 months after start of intervention. Results
(SD = 8.9) obtained in a large study based on the United Kingdom MS Register (50). The HSCL25 Total is a measure of symptoms typical for anxiety and depression. The intervention group had a mean score of 1.76 (SD = 0.54) and the mean score for the control group was 1.77 (SD = 0.44). These scores are approximately 2 SD above the mean scores of 1.18 (SD = 0.25) for persons with no mental disorder in a large Swedish population based study (51) and about 0,5 SD above the mean score of 1.53 (SD = 0.50) for persons with a clinical diagnosis. Neuropsychological characteristics
Neuropsychological characteristics of the study population are presented in Table 3. On group level the study population achieved T-scores within normal range on most of the neuropsychological tests. However, results on several tests that require motor and psychomotor speed (Grooved Pegboard, SDMT, Digit Symbol and TMT A+B) were poorer, ranging from 0.9 to 1.5 SD below the normative mean. Both the control group, that took part in 4week ordinary inpatient MS rehabilitation, and the intervention group, that additionally received a 4 month cognitive intervention program, improved significantly from baseline to four and 7 months after start of the rehabilitation on the Global Executive Composite Score and the Metacognitive Index from the BRIEF-A. However, only the intervention group showed significant Table 2 Baseline characteristics of patients
Demographical and clinical characteristics
There were no significant baseline differences between the intervention group and the control group regarding age, education, gender, work, sick leave/disability benefit, marriage, number of years since diagnosis, EDSS, Primary Progressive MS, Relapsing Remitting MS, Secondary Progressive MS, Intelligence Quotient Global Executive Composite Score (BRIEF-A), Metacognitive Index (BRIEF-A), or MSIS-29 Psychological Scale or HSCL-25 total score (Table 2). The mean scores on the executive subscales from the BRIEF-A inventory were approximately 1 SD above the normative mean for both the intervention group and the control group. On the psychological subscale of the MSIS-29, the group mean for the intervention group was 21.6 (SD = 7.7), and 21.4 (SD = 6.9) for the control group, both somewhat lower than the mean score of 24.8
Control group (n = 60) Mean age (range) Years of education (range) Female (%) Work (%) Sick leave/disability benefit (%) Married/living with a partner (%) Years since diagnosis (SD) EDSS (SD) Primary Progressive MS (%) Relapsing Remitting MS (%) Secondary Progressive MS (%) IQ (SD) GEC (BRIEF-A), T-score (SD) MI (BRIEF-A), T-score (SD) MSIS-29 Psychological scale (SD) HSCL-25 total score (SD)
52.5 13.5 48 7 53 46 12.0 4.2 10 32 18 111.8 60.9 61.8 21.4 1.77
(32–71) (8–18) (80.0) (11.7) (88.3) (76.7) (9.7) (1.7) (16.7) (53.3) (30.0) (10.7) (11.5) (11.6) (6.9) (0.44)
Intervention group (n = 60) 53.9 13.1 40 6 54 44 10.6 4.4 18 27 15 111.8 60.7 62.3 21.6 1.76
(33–70) (9–18) (66.7) (10.0) (90.0) (73.3) (7.7) (1.7) (30.0) (45.0) (25.0) (12.5) (11.1) (11.3) (7.7) (0.54)
P-values n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s.
EDSS, Expanded Disability Status Scale; GEC (BRIEF-A), General Executive Composite from the Behavior Rating Inventory of Executive Function; MI, Metacognition Index; MSIS-29, Multiple Sclerosis Impact Scale-29; HSCL-25, Hopkins Symptoms Checklist-25.
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Hanssen et al. improvement after four and 7 months on the MSIS-29 Psychological Scale and the HSCL-25 total score (Table 4). Differences in change, between the control group and the intervention group, after four and Table 3 Neuropsychological characteristics of the study population Mean T-scores (SD) if not otherwise specified
Test (n) WASI Verbal IQ (114) WASI Performance IQ (115) WASI Full scale IQ (112) WAIS Digit span (115) WMS-III Spatial span (115) SDMT Written (105) SDMT Oral (105) WAIS Symbol digit (110) TMT-A (113) TMT-B (114) D-KEFS Stroop CW (112) D-KEFS Stroop CW/Switching (112) Logical Memory, Immediate Recall (115) Logical Memory Delayed Recall (115) HVLT Total Recall (115) HVLT-R Delayed Recall (115) HVLT-R Retention (%) (112) RCFT Delayed Recall (113) RCFT Recognition Trial (111) D-KEFS Tower Test (107) Peg Board Dominant Hand (110) Peg Board Non-dominant Hand (108) COWAT Letters (115) COWAT Animals (114)
111 110 112 43 50 38 42 40 41 41 48 45 55 55 47 48 49 47 46 54 36 35 45 50
(11.1) (12.4) (11.6) (6.8) (9.2) (14.1) (13.5) (9.9) (13.9) (13.8) (11.5) (12.2) (8.9) (8.6) (11.2) (11.9) (11.7) (14.3) (11.1) (7.5) (15.7) (13.9) (10.3) (14.1)
WASI, Wechsler Abbreviated Scale of Intelligence; WMS, Wechsler Memory Scale; SDMT, Symbol Digit Modalities Test; WAIS, Wechsler Adult Intelligence Scale; TMT, Trail Making Test; D-KEFS, Delis–Kaplan Executive Function System; HVLT-R, Hopkins Verbal Learning Test Revised; RCFT, Rey Complex Figure Test and Recognition Trial; COWAT, Controlled Oral Word Association Test. Table 4 Change from baseline to four and 7 months for the control group and the intervention group
Control group GEC (BRIEF-A), T-score (SD) MI (BRIEF-A), T-score (SD) MSIS-29 Psychological scale (SD) HSCL-25 total score (SD)
Intervention group GEC (BRIEF-A), T-score (SD) MI (BRIEF-A), T-score (SD) MSIS-29 Psychological Subscale (SD) HSCL-25 total score (SD)
Baseline N = 60
Four months N = 51
Seven months N = 48
60.0 (10.6) 61.0 (10.5) 20.9 (6.6)
56.7 (11.7)** 57.8 (10.7)** 19.9 (7.7) n.s.
55.2 (11.5)** 56.7 (10.9)** 20.6 (8.0) n.s.
1.75 (0.42)
1.74 (0.50) n.s.
1.65 (0.53) n.s.
Baseline N = 60
Four months N = 51
Seven months N = 54
61.1 (11.0) 62.7 (11.3) 21.3 (7.0)
56.4 (11.7)** 58.2 (11.8)** 18.3 (6.9)**
56.3 (11.8)** 57.7 (11.9)** 18.3 (7.2)**
1.76 (0.53)
1.60 (0.49)*
1.62 (0.47)**
BRIEF-A, Behavior Rating Inventory of Executive Function – Adult version; GEC, General Executive Composite; MI, Metacognition Index; HSCL-25, Hopkins Symptom Checklist- 25; MSIS-29, Multiple Sclerosis Impact Scale-29. *P < 0.05 **P < 0.01.
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7 months on the outcome variables, are shown in Table 5. Both groups improved significantly on the executive variables at the two measurement points, and there were no significant differences in change between the groups on these variables. However, on the scale measuring psychological aspects of HRQoL (MSIS-29), the intervention group improved close to significantly (P = 0.06) more than the control group after 4 months and significantly more than the control group after 7 months (P = 0.03). Similar results were found for the HSCL-25, primarily measuring symptoms of anxiety and depression: the intervention group improved significantly more after 4 months (P = 0.05). The HSCL-25 score improved after 7 months as well, however, not significantly. Discussion
The current RCT investigated the effects of a multicomponent cognitive rehabilitation program aiming to improve cognitive and executive coping, psychological well-being and psychological aspects of HRQoL in MS patients with cognitive complaints. The main findings were that: 1. Self-reported executive functioning improved significantly from baseline to four and 7 months both in the intervention group and in the control group, whereas significant improvement in psychological well-being and psychological aspects of HRQoL occurred only in the intervention group. 2. The intervention group showed significantly or nearly significantly larger improvements than the control group in psychological aspects of HRQoL at four and 7 months after the start of the rehabilitation program, as well as significant improvement in psychological well-being after 4 months. The main difference between the cognitive rehabilitation program and the general multidisciplinary rehabilitation program in the current study was the guidance through the process of formulating and implementing individual GAS goals for coping with cognitive challenges in everyday life. Consistent with previous studies, we found that GAS was a feasible outcome measure in MS rehabilitation (52) and that the GAS goals set by the participants in the intervention group were well achieved and maintained throughout the study period (53–55). A strength of the current study was the utilization of a randomized controlled design. The sample size (n = 120) was large enough to ensure
Cognitive MS rehabilitation Table 5 Differences in change between the control group and the intervention group from baseline to four and 7 months after start of intervention Control group Variables
N
GEC (BRIEF-A), T-score (SD) MI (BRIEF-A), T-score (SD) MSIS-29 Psych. scale, raw score (SD) HSCL-25 Total score, raw score (SD)
60 60 59 60
Changes after 7 months GEC (BRIEF-A), T-score (SD) MI (BRIEF-A), T-score (SD) MSIS-29 Psych. scale, raw score (SD) HSCL-25 Total score, raw score (SD)
Baseline 60.9 61.8 21.4 1.8
(11.5) (11.6) (7.0) (0.4)
Baseline 60 60 59 60
60.9 61.8 21.4 1.8
(11.5) (11.6) (7.0) (0.42)
Intervention group
4 months
N
N
56.8 57.8 20.0 1.74
51 51 50 51
59 59 60 59
(11.7) (10.7) (7.7) (0.5)
7 months 55.2 56.7 20.5 1.7
(11.5) (10.9) (8.0) (0.5)
sufficient statistical power to reveal differences between the groups. The intervention group and the control group were similar at baseline, and the dropout rate was acceptable. The participants underwent comprehensive neuropsychological assessment with well-validated instruments. Additionally, methodologically sound instruments were used for collection of data on goal attainment and primary outcomes. The timing of individual sessions, group sessions, and outcome assessment was identical for all the patients. The possibility of placebo effects cannot be ruled out completely. Due to the nature of the intervention, blinding of treatment allocation was not possible, and participants were aware of their group affiliation as well as the objectives of the intervention. To reduce the risk for positive response biases, objective measurement tools were utilized and the participants were encouraged to give accurate answers. Nonetheless, the intervention group did receive an additional intervention, whereas no control or sham intervention was provided to the control group. The study population represented a selected group of highly motivated patients, recruited from a multidisciplinary inpatient rehabilitation program offered for MS patients with a low to moderate neurological symptom load, as measured by EDSS
