Improved quality of life and psychological symptoms following mindfulness and cognitive rehabilitation in multiple sclerosis and their mediating role for cognition: a randomized controlled trial.

BACKGROUND: Multiple sclerosis (MS) frequently gives rise to depressive and anxiety symptoms, but these are often undertreated. This study investigated the effect of mindfulness-based cognitive therapy (MBCT) and cognitive rehabilitation therapy (CRT) on psychological outcomes and quality of life (QoL), and whether they mediate treatment effects on MS-related cognitive problems. METHODS: This randomized controlled trial included MS patients with cognitive complaints (n = 99) and compared MBCT (n = 32) and CRT (n = 32) to enhanced treatment as usual (n = 35). Baseline, post-treatment and 6-months follow-up assessments included patient-reported outcome measures (PROMS) and cognitive outcomes (self-reported and neuropsychological assessment). PROMS concerned psychological symptoms, well-being, QoL, and daily life function. Linear mixed models indicated intervention effects on PROMS and mediation effects of PROMS on cognitive outcomes. RESULTS: MBCT positively affected depressive symptoms (Cohen's d (d) = -0.46), fatigue (d = -0.39), brooding (d = -0.34), mindfulness skills (d = 0.49), and mental QoL (d = -0.73) at post-treatment. Effects on mindfulness skills remained significant 6 months later (d = 0.42). CRT positively affected depressive symptoms (d = -0.46), mindfulness skills (d = 0.37), and mental QoL (d = -0.45) at post-treatment, but not at 6-month follow-up. No effects on anxiety, well-being, self-compassion, physical QoL, and daily life function were found. Treatment effects on self-reported, but not objective, cognition were mediated by psychological symptoms and mindfulness skills. CONCLUSIONS: MBCT and CRT reduced a wide array of psychological symptoms and improved mental QoL. These improvements seemed to impact self-reported cognitive problems after both treatments, whereas objective cognitive improvements after MBCT seemed independent of improvement in psychological symptoms. Future studies should investigate long-term sustainability of these beneficial effects. TRIAL REGISTRATION: The trial was prospectively registered in the Dutch Trial registry on 31 May 2017 (NL6285; https://trialsearch.who.int/Trial2.aspx?TrialID=NTR6459 ).

Neurophysiological brain function predicts response to cognitive rehabilitation and mindfulness in multiple sclerosis: a randomized trial.

BACKGROUND: Cognitive treatment response varies highly in people with multiple sclerosis (PwMS). Identification of mechanisms is essential for predicting response. OBJECTIVES: This study aimed to investigate whether brain network function predicts response to cognitive rehabilitation therapy (CRT) and mindfulness-based cognitive therapy (MBCT). METHODS: PwMS with cognitive complaints completed CRT, MBCT, or enhanced treatment as usual (ETAU) and performed three measurements (baseline, post-treatment, 6-month follow-up). Baseline magnetoencephalography (MEG) measures were used to predict treatment effects on cognitive complaints, personalized cognitive goals, and information processing speed (IPS) using mixed models (secondary analysis REMIND-MS study). RESULTS: We included 105 PwMS (96 included in prediction analyses; 32 CRT, 31 MBCT, 33 ETAU), and 56 healthy controls with baseline MEG. MEG did not predict reductions in complaints. Higher connectivity predicted better goal achievement after MBCT (p = 0.010) and CRT (p = 0.018). Lower gamma power (p = 0.006) and higher connectivity (p = 0.020) predicted larger IPS benefits after MBCT. These MEG predictors indicated worse brain function compared to healthy controls (p < 0.05). CONCLUSIONS: Brain network function predicted better cognitive goal achievement after MBCT and CRT, and IPS improvements after MBCT. PwMS with neuronal slowing and hyperconnectivity were most prone to show treatment response, making network function a promising tool for personalized treatment recommendations. TRIAL REGISTRATION: The REMIND-MS study was prospectively registered in the Dutch Trial registry (NL6285; https://trialsearch.who.int/Trial2.aspx?TrialID=NTR6459 ).

Game-supported cognitive strategy training for slowed information processing speed after acquired brain injury: study protocol for a randomised controlled trial.

INTRODUCTION: Many individuals with acquired brain injury tend to experience problems with slowed information processing speed (IPS). A potentially beneficial and cost-effective supplement for cognitive rehabilitation of impaired IPS may be the implementation of serious gaming that focuses on compensatory learning as part of cognitive training. However, most digital platforms used during cognitive rehabilitation focus on restoring cognitive function and evidence for skill transfer from digital practice to everyday life is lacking. This study aims to investigate the efficacy of a game-supported cognitive strategy training. The training combines a well-validated time pressure management cognitive strategy training, targeting slowed IPS, with a novel game and a mobile application. The game-supported training focuses on the generalisation of strategy-use to untrained tasks in everyday life. METHODS AND ANALYSIS: The study is designed as a randomised controlled trial in which the experimental group (Karman Line - Tempo module: an 8-week game-supported cognitive strategy training) will be compared with an active control group (CogniPlus training: an 8-week computerised cognitive function training). Data from 60 individuals with acquired brain injury (30 per group, ages between 16 and 75) will be collected at baseline (T0), post-treatment (T1) and at 3-month follow-up (T2). The primary outcome measure is an objective assessment of compensatory strategy use in an untrained experimental task. The secondary outcome is the attainment of trained and untrained treatment goals assessed by goal attainment scaling. Pre-training and post-training data will be analysed using a 2×2 repeated measure analysis of variance. ETHICS AND DISSEMINATION: This study has been approved by the medical review ethics committee CMO Region Arnhem and Nijmegen (NL74818.091.20) and is registered in the Netherlands Trial Register. Research findings will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: NL9437; The Netherlands Trial Register.

Cognitive rehabilitation and mindfulness reduce cognitive complaints in multiple sclerosis (REMIND-MS): A randomized controlled trial.

BACKGROUND: Cognitive problems, both complaints and objective impairments, are frequent and disabling in patients with multiple sclerosis (MS) and profoundly affect daily living. However, intervention studies that focus on cognitive problems that patients experience in their daily lives are limited. This study therefore aimed to investigate the effectiveness of cognitive rehabilitation therapy (CRT) and mindfulness-based cognitive therapy (MBCT) on patient-reported cognitive complaints in MS. METHODS: In this randomized-controlled trial, MS patients with cognitive complaints completed questionnaires and underwent neuropsychological assessments at baseline, post-treatment and 6-month follow-up. Patient-reported cognitive complaints were primarily investigated. Secondary outcomes included personalized cognitive goals and objective cognitive function. CRT and MBCT were compared to enhanced treatment as usual (ETAU) using linear mixed models. RESULTS: Patients were randomized into CRT (n = 37), MBCT (n = 36) or ETAU (n = 37), of whom 100 completed the study. Both CRT and MBCT positively affected patient-reported cognitive complaints compared to ETAU at post-treatment (p<.05), but not 6 months later. At 6-month follow-up, CRT had a positive effect on personalized cognitive goals (p=.028) and MBCT on processing speed (p=.027). Patients with less cognitive complaints at baseline benefited more from CRT on the Cognitive Failures Questionnaire (i.e. primary outcome measuring cognitive complaints) at post-treatment (p=.012-.040), and those with better processing speed at baseline benefited more from MBCT (p=.016). CONCLUSION: Both CRT and MBCT alleviated cognitive complaints in MS patients immediately after treatment completion, but these benefits did not persist. In the long term, CRT showed benefits on personalized cognitive goals and MBCT on processing speed. These results thereby provide insight in the specific contributions of available cognitive treatments for MS patients.

Two Ecological Tools for Testing Slowness of Information Processing in Italian Patients with Moderate-to-Severe Traumatic Brain Injury.

Slowness of Information Processing (SIP) is frequently experienced after traumatic brain injury (TBI); however, the impact of SIP on everyday functioning may be underestimated by standard neuropsychological tests. OBJECTIVE: we aimed to adapt two ecological instruments assessing SIP in Italian patients with moderate-to-severe TBI, as formerly proposed by Winkens and colleagues for persons with stroke, testing also its possible relation with other neuropsychological processes and functional outcomes. METHOD: we performed an observational study on 37 patients with moderate-to-severe TBI and 35 demographically matched healthy controls, who underwent the Mental Slowness Observation Test (MSOT) and the Mental Slowness Questionnaire (MSQ), which had been adapted through a pilot study on independent sample of participants; extensive neuropsychological and functional evaluations were performed as well. RESULTS: We found good clinical and psychometric properties of the Italian adaptation of the MSOT and MSQ; also, performance on MSOT significantly correlated with executive functions. Moreover, patients with TBI are significantly slower and less accurate than healthy controls on the MSOT, in particular in tasks with time limits. Even if the subjective feeling of SIP does not differ between patients and controls, we found a significant correlation between MSQ and MSOT. Finally, the performances on the MSOT correlated with measures of functional outcome and community integration. CONCLUSIONS: the results support the use of the MSOT and the MSQ to measure SIP in an ecological fashion in patients with TBI, so that specific treatments for persons with acquired brain injury can be prescribed.

Neurobehavioral Initiation and Motivation Problems After Acquired Brain Injury.

Motivation is a primary and permanent source of human behavior and adaptation. Motivational deficits, along with deficiencies in initiation, frequently occur in individuals with acquired brain injury (ABI). These neurobehavioral problems are associated with consequences at the participation level: patients are reluctant to engage in rehabilitation, and their subsequent social reintegration is often at risk. The same problems may also become a heavy burden for the families of individuals with ABI. In the present paper, we will critically review both the current definitions and the instruments used to measure motivational disorders following ABI. We will also describe the neural system underlying motivation and its impairments. What emerges is the need to develop specific rehabilitative treatments, still absent at the moment, with the ultimate aim of ensuring a better quality of life for both the patients and their proxies.

Incorporation of a working memory strategy in GMT to facilitate serial-order behaviour in brain-injured patients.

Goal Management Training (GMT) is an effective method for improving disorganised behaviour in multistep real-life tasks after brain damage. In the present study we incorporated Working Memory Training (WMT) in GMT to explore their combined efficacy in facilitating the serial-order maintenance of the steps that had to be learned. GMT+WMT was compared to a control WMT designed for other purposes. For this purpose 18 brain-injured patients (aged 20-54), who were at least 4 months post-onset, were randomly assigned to either the GMT+WMT or the WMT treatment. Inclusion was based on a baseline score of less than six correct steps on each of two multistep everyday tasks. Alternative versions of these tasks were used as primary outcome tasks. Pre-treatment and post-treatment comparisons of scores on these primary tasks and on several secondary neuropsychological measures were collected. The results show that post-treatment the GMT+WMT group performed significantly better than the WMT group on the primary outcome measures and on several ecologically valid executive tests that demanded a step-by-step maintenance of multiple actions. Time effects were found for both groups on the secondary measures. Other measures showed no significant differences. We conclude that our results support the efficacy of the combined GMT+WMT in facilitating performance in everyday multistep tasks.

Caregivers' effects of augmented cognitive-behavioural therapy for post-stroke depressive symptoms in patients: secondary analyses to a randomized controlled trial.

OBJECTIVE: To investigate the concomitant effects of two patient-directed interventions for post-stroke depressive symptoms on caregivers' well-being. DESIGN: Secondary analyses of the results of a randomized controlled trial. SUBJECTS: Fifty caregivers of stroke patients receiving outpatient rehabilitation. INTERVENTIONS: Stroke patients and their caregivers were randomly allocated to either cognitive-behavioural therapy augmented with movement or occupational therapy ( n = 23) or computerized cognitive training ( n = 27) to alleviate depressive symptoms in patients. MAIN MEASURES: Emotional burden (Involvement Evaluation Questionnaire), practical burden (Caregiver Strain Index), mental health (General Health Questionnaire) and emotional complaints (Hospital Anxiety and Depression Scale). RESULTS: Caregivers of patients who received cognitive-behavioural therapy reported significantly higher mental health levels (mean difference (MD) = 1.78, 95% confidence interval (CI) = 0.43-3.13, P = 0.01) and less worrying about patients' well-being (MD = 1.9, 95% CI = 0.56-3.24, P < 0.01). In addition, there were positive time effects on the Involvement Evaluation Questionnaire for Brain Injury, particularly the subscales Worrying, Supervision and Tension. CONCLUSION: The results suggest that augmented cognitive-behavioural therapy aimed at improving patients' emotional, behavioural and social functioning positively affects some aspects of caregivers' well-being.

Social cognition and emotion regulation: a multifaceted treatment (T-ScEmo) for patients with traumatic brain injury.

BACKGROUND: Many patients with moderate to severe traumatic brain injury have deficits in social cognition. Social cognition refers to the ability to perceive, interpret, and act upon social information. Few studies have investigated the effectiveness of treatment for impairments of social cognition in patients with traumatic brain injury. Moreover, these studies have targeted only a single aspect of the problem. They all reported improvements, but evidence for transfer of learned skills to daily life was scarce. We evaluated a multifaceted treatment protocol for poor social cognition and emotion regulation impairments (called T-ScEmo) in patients with traumatic brain injury and found evidence for transfer to participation and quality of life. PURPOSE: In the current paper, we describe the theoretical underpinning, the design, and the content of our treatment of social cognition and emotion regulation (T-ScEmo). THEORY INTO PRACTICE: The multifaceted treatment that we describe is aimed at improving social cognition, regulation of social behavior and participation in everyday life. Some of the methods taught were already evidence-based and derived from existing studies. They were combined, modified, or extended with newly developed material. PROTOCOL DESIGN: T-ScEmo consists of 20 one-hour individual sessions and incorporates three modules: (1) emotion perception, (2) perspective taking and theory of mind, and (3) regulation of social behavior. It includes goal-setting, psycho-education, function training, compensatory strategy training, self-monitoring, role-play with participation of a significant other, and homework assignments. RECOMMENDATIONS: It is strongly recommended to offer all three modules, as they build upon each other. However, therapists can vary the time spent per module, in line with the patients' individual needs and goals. In future, development of e-learning modules and virtual reality sessions might shorten the treatment.

The clinical value of the patient-reported multiple sclerosis neuropsychological screening questionnaire.

BACKGROUND: Cognitive problems are difficult to identify in patients with multiple sclerosis (MS). OBJECTIVE: To investigate the clinical applicability of the patient-reported MS Neuropsychological Screening Questionnaire (MSNQ-P). METHODS: Cut-off scores were determined to differentiate between cognitively impaired (n = 90), mildly cognitively impaired (n = 115), and cognitively preserved (n = 147) MS patients using receiver operating characteristic analyses. RESULTS: We could not define specific and sensitive cut-off scores. Higher scores (≥27) did indicate cognitive impairment. Among patients with a higher education, lower scores (<12) indicated intact cognition. CONCLUSION: Certain scores can indicate intact or impaired cognitive function. Still, MSNQ-P scores should be interpreted with caution.

Participation after traumatic brain injury: the surplus value of social cognition tests beyond measures for executive functioning and dysexecutive behavior in a statistical prediction model.

Objective: This study evaluates the contribution of measures for social cognition (SC), executive functioning (EF) and dysexecutive behavior to the statistical prediction of social and vocational participation in patients with traumatic brain injury (TBI), taking into account age and injury severity.Method: A total of 63 patients with moderate to severe TBI participated. They were administered a semi-structured Role Resumption List for social (RRL-SR) and vocational participation (RRL-RTW). EF was measured with planning- and switching tasks. Assessment of SC included tests for facial affect recognition and Theory of Mind (ToM). Dysexecutive behavior was proxy-rated with a questionnaire. Additionally, healthy controls were assessed with the same protocol.Results: Patients with TBI performed significantly worse on tests and had significantly more behavioral problems compared to healthy controls. Hierarchical multiple regression analyses for the TBI group revealed that SC accounted for 22% extra variance in RRL-RTW and 10% extra variance in RRL-SR, which was significant over and above the amounts of variance explained by EF, dysexecutive behavior, age and injury severity.Conclusions: Our findings underline the added value of measures of SC and dysexecutive behavior in the prediction of social and vocational participation post-TBI. In particular, impairments in ToM, and dysexecutive behavior were related to a lower participation making them important targets for rehabilitation.

Memory Strategy Training in Older Adults with Subjective Memory Complaints: A Randomized Controlled Trial.

OBJECTIVES: Subjective memory complaints (SMC) in older adults are associated with a decline in everyday functioning and an increased risk for future cognitive decline. This study examines the effect of a memory strategy training compared to a control memory training on memory functioning in daily life. METHODS: This was a randomized controlled trial with baseline, post-treatment, and 6-month follow-up assessments conducted in 60 older adults (50-87 years) with SMC. Participants were randomly assigned to either seven sessions of memory strategy training or seven sessions of control memory training. Both interventions were given in small groups and included psycho-education. Primary outcome measure was memory functioning in daily life. Objective measures of memory performance and self-reported measures of strategy use were included as secondary outcome measures. RESULTS: Participants in each intervention group reported an improvement in personal memory goals (p<.0005), up to 6 months after training. An interaction effect showed that participants following memory strategy training reported a larger improvement in personal memory goals (p=.002). Both intervention groups improved on two memory tests (p<.001 and p<.01). In the memory strategy training group, an increase in strategy use in daily life was the strongest predictor (p<.05) of improvement in subjective memory functioning. CONCLUSIONS: Older adults with subjective memory complaints benefit from memory strategy training, especially in their memory functioning in daily life. (JINS, 2018, 24, 1110-1120).

The influence of cognitive reserve and age on the use of memory strategies.

BACKGROUND: Whether older adults use effective memory strategies to compensate for their memory decline partly depends on their executive functioning (EF). However, many studies have overlooked the role of cognitive reserve (CR). This study examines the effects of age, EF, and CR on memory strategy use. METHODS: A total of 83 participants (aged 18-85 years) were included. Strategy use was assessed using three measures: (1) self-reported strategy use in daily life, (2) self-reported and observed strategy use in a simulated daily life situation, and (3) self-reported strategy use during a word-pair task. RESULTS: Results showed that CR was the strongest predictor of strategy use, both in daily life and during memory tasks. Although effects of age and EF were found, most of these effects disappeared when CR was added to the model. Furthermore, a higher CR was related to the use of more complex strategies and to more effective strategies in relation to task performance. CONCLUSIONS: Higher levels of CR seem to enable individuals to use effective strategies. These results highlight the importance of the role of CR in compensating for the aging-related memory decline.

Destination memory in social interaction: better memory for older than for younger destinations in normal aging?

Destination memory, a memory component allowing the attribution of information to its appropriate receiver (e.g., to whom did I lend my pen?), is compromised in normal aging. The present paper investigated whether older adults might show better memory for older destinations than for younger destinations. This hypothesis is based on empirical research showing better memory for older faces than for younger faces in older adults. Forty-one older adults and 44 younger adults were asked to tell proverbs to older and younger destinations (i.e., coloured faces). On a later recognition test, participants had to decide whether they had previously told some proverb to an older/younger destination or not. Prior to this task, participants reported their frequency of contact with other-age groups. The results showed lower destination memory in older adults than in younger adults. Interestingly, older adults displayed better memory for older than for younger destinations. The opposite pattern was seen in younger adults. The low memory for younger destinations, as observed in older adults, was significantly correlated with limited exposure to younger individuals. These findings suggest that for older adults, the social experience can play a crucial role in the destination memory, at least as far as exposure to other-age groups is concerned.

Cognitive rehabilitation and mindfulness in multiple sclerosis (REMIND-MS): a study protocol for a randomised controlled trial.

BACKGROUND: Cognitive problems frequently occur in patients with multiple sclerosis (MS) and profoundly affect their quality of life. So far, the best cognitive treatment options for MS patients are a matter of debate. Therefore, this study aims to investigate the effectiveness of two promising non-pharmacological treatments: cognitive rehabilitation therapy (CRT) and mindfulness-based cognitive therapy (MBCT). Furthermore, this study aims to gain additional knowledge about the aetiology of cognitive problems among MS patients, since this may help to develop and guide effective cognitive treatments. METHODS/DESIGN: In a dual-centre, single-blind randomised controlled trial (RCT), 120 MS patients will be randomised into one of three parallel groups: CRT, MBCT or enhanced treatment as usual (ETAU). Both CRT and MBCT consist of a structured 9-week program. ETAU consists of one appointment with an MS specialist nurse. Measurements will be performed at baseline, post-intervention and 6 months after the interventions. The primary outcome measure is the level of subjective cognitive complaints. Secondary outcome measures are objective cognitive function, functional brain network measures (using magnetoencephalography), psychological symptoms, well-being, quality of life and daily life functioning. DISCUSSION: To our knowledge, this will be the first RCT that investigates the effect of MBCT on cognitive function among MS patients. In addition, studying the effect of CRT on cognitive function may provide direction to the contradictory evidence that is currently available. This study will also provide information on changes in functional brain networks in relation to cognitive function. To conclude, this study may help to understand and treat cognitive problems among MS patients. TRIAL REGISTRATION: This trial was prospectively registered at the Dutch Trial Registration (number NTR6459 , registered on 31 May 2017).

Effectiveness of a Treatment for Impairments in Social Cognition and Emotion Regulation (T-ScEmo) After Traumatic Brain Injury: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effects of a multifaceted Treatment for Social cognition and Emotion regulation (T-ScEmo) in patients with a traumatic brain injury. PARTICIPANTS: Sixty-one patients with moderate to severe traumatic brain injury randomly assigned to an experimental T-ScEmo intervention or a Cogniplus control condition. INTERVENTIONS: T-ScEmo is a compensatory strategy training for impairments in emotion recognition, theory of mind, and social behavioral skills. Cogniplus is a computerized cognitive function training. Both interventions were given in 16 to 20 weekly 1-hour sessions. MAIN MEASURES: Social cognition tests and questionnaires for social behavior (self- and proxy-rated) administered at baseline, immediately posttreatment, and at 3 to 5 months of follow-up. RESULTS: Compared with the Cogniplus group, the T-ScEmo group improved significantly on facial affect recognition, theory of mind, proxy-rated empathic behavior, societal participation, and treatment goal attainment, which lasted up to 5 months after treatment. At follow-up, the T-ScEmo group also reported higher quality of life and their life partners rated relationship quality to be higher than the Cogniplus group. CONCLUSION: This study shows that impairments in social cognition can be effectively dealt with by using a comprehensive treatment protocol, leading to improvements in everyday life social functioning.

Memory strategy use in older adults with subjective memory complaints.

BACKGROUND: Subjective memory complaints (SMC) are common among older adults, but it is unclear to what extent adults with SMC spontaneously use memory strategies to compensate for their memory problems. As SMC may be a risk factor for memory decline later, it is important to extend our knowledge about spontaneous compensatory mechanisms in older adults with SMC. METHOD: Self-reported strategy use and observed strategy use were assessed in 38 adults with and 38 without SMC. RESULTS: Adults with SMC used more strategies in daily life than those without. In the SMC group, memory complaints were positively correlated with strategy use. Only in adults without SMC, a significant correlation was found between observed strategy use and task performance. CONCLUSION: Strategy use in older adults with SMC may be compensatory in nature, but did not increase their objective memory performance. Therefore, older adults with SMC might benefit from interventions aimed at optimizing strategy use.

Intelligence moderates the benefits of strategy instructions on memory performance: an adult-lifespan examination.

Whether older adults can compensate for their associative memory deficit by using memory strategies efficiently might depend on their general cognitive abilities. This study examined the moderating role of an IQ estimate on the beneficial effects of strategy instructions. A total of 142 participants (aged 18-85 years) received either intentional learning or strategy ("sentence generation") instructions during encoding of word pairs. Whereas young adults with a lower IQ benefited from strategy instructions, those with a higher IQ did not, presumably because they already use strategies spontaneously. Older adults showed the opposite effect: following strategy instructions, older adults with a higher IQ showed a strong increase in memory performance (approximately achieving the level of younger adults), whereas older adults with a lower IQ did not, suggesting that they have difficulties implementing the provided strategies. These results highlight the importance of the role of IQ in compensating for the aging-related memory decline.

Preserved and attenuated electrophysiological correlates of visual spatial attention in elderly subjects.

Healthy aging is associated with changes in many neurocognitive functions. While on the behavioral level, visual spatial attention capacities are relatively stable with increasing age, the underlying neural processes change. In this study, we investigated attention-related modulations of the stimulus-locked event-related potential (ERP) and occipital oscillations in the alpha band (8-14Hz) in young and elderly participants. Both groups performed a visual attention task equally well and the ERP showed comparable attention-related modulations in both age groups. However, in elderly subjects, oscillations in the alpha band were massively reduced both during the task and in the resting state and the typical task-related lateralized pattern of alpha activity was not observed. These differences between young and elderly participants were observed on the group level as well as on the single trial level. The results indicate that younger and older adults use different neural strategies to reach the same performance in a covert visual spatial attention task.