A Biopsychosocial Approach to Persistent Post-COVID-19 Fatigue and Cognitive Complaints: Results of the Prospective Multicenter NeNeSCo Study.

OBJECTIVE: To evaluate whether psychological and social factors complement biomedical factors in understanding post-COVID-19 fatigue and cognitive complaints. Additionally, to incorporate objective (neuro-cognitive) and subjective (patient-reported) variables in identifying factors related to post-COVID-19 fatigue and cognitive complaints. DESIGN: Prospective, multicenter cohort study. SETTING: Six Dutch hospitals. PARTICIPANTS: 205 initially hospitalized (March-June 2020), confirmed patients with SARS-CoV-2, aged ≥18 years, physically able to visit the hospital, without prior cognitive deficit, magnetic resonance imaging (MRI) contraindication, or severe neurologic damage post-hospital discharge (N=205). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Nine months post-hospital discharge, a 3T MRI scan and cognitive testing were performed and patients completed questionnaires. Medical data were retrieved from medical dossiers. Hierarchical regression analyses were performed on fatigue severity (Fatigue Severity Scale; FSS) and cognitive complaints (Cognitive Consequences after Intensive Care Admission; CLC-IC; dichotomized into CLC-high/low). Variable blocks: (1) Demographic and premorbid factors (sex, age, education, comorbidities), (2) Illness severity (ICU/general ward, PROMIS physical functioning [PROMIS-PF]), (3) Neuro-cognitive factors (self-reported neurological symptoms, MRI abnormalities, cognitive performance), (4) Psychological and social factors (Hospital Anxiety and Depression Scale [HADS], Utrecht Coping List, Social Support List), and (5) Fatigue or cognitive complaints. RESULTS: The final models explained 60% (FSS) and 48% (CLC-IC) variance, with most blocks (except neuro-cognitive factors for FSS) significantly contributing. Psychological and social factors accounted for 5% (FSS) and 11% (CLC-IC) unique variance. Higher FSS scores were associated with younger age (P=.01), lower PROMIS-PF (P<.001), higher HADS-Depression (P=.03), and CLC-high (P=.04). Greater odds of CLC-high were observed in individuals perceiving more social support (OR=1.07, P<.05). CONCLUSIONS: Results show that psychological and social factors add to biomedical factors in explaining persistent post-COVID-19 fatigue and cognitive complaints. Objective neuro-cognitive factors were not associated with symptoms. Findings highlight the importance of multidomain treatment, including psychosocial care, which may not target biologically-rooted symptoms directly but may reduce associated distress.

Facilitators and barriers in caring for a person with Huntington's disease: input for a remote support program.

OBJECTIVES: This study aims to provide more insight into possible barriers and facilitators caregivers of people with Huntington's disease (HD) encounter, and what their needs and wishes are regarding a remote support program. METHODS: In total, 27 persons participated in four focus group interviews. Eligible participants were caregivers (n = 19) of a person with HD, and healthcare professionals (n = 8) involved in HD care. Qualitative data were analyzed by two researchers who independently performed an inductive content analysis. RESULTS: Four major themes emerged from the data, including (1) a paradox between taking care of yourself and caring for others; (2) challenges HD caregivers face in daily life, including lack of HD awareness, taboo and shame, feelings of loneliness, concerns about heredity and children, and coping with HD symptoms; (3) facilitators in the caregiving process, including a social network, professional support, openness, talking in early phases, and daily structure; (4) needs regarding a support program. CONCLUSION: These insights will be used to develop a remote support program for HD caregivers, using a blended and self-management approach. Newly developed and tailored support should be aimed at empowering caregivers in their role and help them cope with their situation, taking into account barriers and facilitators.

Navigating Life With Parkinson's Disease: A Focus Group Study on Coping Strategies and Considerations for Self-Management Support.

AIM: To investigate the experiences of people with Parkinson's disease in coping with and adapting to their disease and to identify considerations for a tailored self-management support program. DESIGN: A descriptive phenomenological focus group study. METHODS: Five semi-structured focus groups were conducted between April 2023 and June 2023 in the Netherlands, with 12 people with Parkinson's disease. Two researchers independently performed an inductive content analysis. RESULTS: Three principal categories emerged: (1) Rational realisation versus emotional experience: the coping strategy transition. This category includes three main coping strategies: denial or avoidance coping, acknowledging with less active coping and proactive and task-oriented coping. (2) Factors that influence coping, including mindset and skills, social circles and communication and access to support and care. (3) Considerations for successful self-management of Parkinson's disease, highlighting key areas such as psycho-emotional guidance, nutrition and lifestyle, peer support and maintaining autonomy and sense of identity. CONCLUSION: Coping and adaptation strategies are individual and dynamic processes, with multiple key or turning points during the transition between strategies. Tailored self-management support can enhance coping abilities during these transitions, fostering adaptation to a life with Parkinson's disease. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: A patient-focused version of an existing blended self-management support program for family caregivers will be developed, which will be delivered by healthcare professionals. IMPACT: This study can help healthcare professionals tailor support for people with Parkinson's disease, emphasising their role in facilitating coping and adaptation. Enhancing self-management can improve self-efficacy, quality of life and potentially reduce healthcare utilisation in people with Parkinson's disease. REPORTING METHOD: Findings are reported according to the COREQ guidelines. PATIENT OR PUBLIC CONTRIBUTION: Patients and Parkinson's disease experts participated in the preparation and implications of the findings. All participants could contribute to the self-management support program, either through video interviews or content feedback.

Neurological and (neuro)psychological sequelae in intensive care and general ward COVID-19 survivors.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) affects the brain, leading to long-term complaints. Studies combining brain abnormalities with objective and subjective consequences are lacking. Long-term structural brain abnormalities, neurological and (neuro)psychological consequences in COVID-19 patients admitted to the intensive care unit (ICU) or general ward were investigated. The aim was to create a multidisciplinary view on the impact of severe COVID-19 on functioning and to compare long-term consequences between ICU and general ward patients. METHODS: This multicentre prospective cohort study assessed brain abnormalities (3 T magnetic resonance imaging), cognitive dysfunction (neuropsychological test battery), neurological symptoms, cognitive complaints, emotional distress and wellbeing (self-report questionnaires) in ICU and general ward (non-ICU) survivors. RESULTS: In al, 101 ICU and 104 non-ICU patients participated 8-10 months post-hospital discharge. Significantly more ICU patients exhibited cerebral microbleeds (61% vs. 32%, p < 0.001) and had higher numbers of microbleeds (p < 0.001). No group differences were found in cognitive dysfunction, neurological symptoms, cognitive complaints, emotional distress or wellbeing. The number of microbleeds did not predict cognitive dysfunction. In the complete sample, cognitive screening suggested cognitive dysfunction in 41%, and standard neuropsychological testing showed cognitive dysfunction in 12%; 62% reported ≥3 cognitive complaints. Clinically relevant scores of depression, anxiety and post-traumatic stress were found in 15%, 19% and 12%, respectively; 28% experienced insomnia and 51% severe fatigue. CONCLUSION: Coronavirus disease 2019 ICU survivors had a higher prevalence for microbleeds but not for cognitive dysfunction compared to general ward survivors. Self-reported symptoms exceeded cognitive dysfunction. Cognitive complaints, neurological symptoms and severe fatigue were frequently reported in both groups, fitting the post-COVID-19 syndrome.

Performance and Symptom Validity Assessment in Patients with Apathy and Cognitive Impairment.

OBJECTIVE: Performance and symptom validity tests (PVTs and SVTs) measure the credibility of the assessment results. Cognitive impairment and apathy potentially interfere with validity test performance and may thus lead to an incorrect (i.e., false-positive) classification of the patient's scores as non-credible. The study aimed at examining the false-positive rate of three validity tests in patients with cognitive impairment and apathy. METHODS: A cross-sectional, comparative study was performed in 56 patients with dementia, 41 patients with mild cognitive impairment, and 41 patients with Parkinson's disease. Two PVTs - the Test of Memory Malingering (TOMM) and the Dot Counting Test (DCT) - and one SVT - the Structured Inventory of Malingered Symptomatology (SIMS) - were administered. Apathy was measured with the Apathy Evaluation Scale, and severity of cognitive impairment with the Mini Mental State Examination. RESULTS: The failure rate was 13.7% for the TOMM, 23.8% for the DCT, and 12.5% for the SIMS. Of the patients with data on all three tests (n = 105), 13.5% failed one test, 2.9% failed two tests, and none failed all three. Failing the PVTs was associated with cognitive impairment, but not with apathy. Failing the SVT was related to apathy, but not to cognitive impairment. CONCLUSIONS: In patients with cognitive impairment or apathy, failing one validity test is not uncommon. Validity tests are differentially sensitive to cognitive impairment and apathy. However, the rule that at least two validity tests should be failed to identify non-credibility seemed to ensure a high percentage of correct classification of credibility.

Feasibility of a Cognitive Training Game in Parkinson's Disease: The Randomized Parkin'Play Study.

Cognitive training (CT) shows modest positive effects on cognitive function in patients with Parkinson's disease (PD). Gamification may enhance adherence to traditional CT, but this has not been studied yet. Here, we investigated the feasibility of a gamified CT. We performed a randomized controlled trial including PD patients with mild cognitive impairment. Participants were randomly allocated to a 12-week home-based gamified CT intervention or waiting-list control group. Assessments were performed at baseline and at weeks 12 and 24. Forty-one patients were included (21 intervention and 20 waiting-list controls). Sixty-three percent of the intervention group trained >50% of the recommended sessions, while 81% voluntarily continued training after 12 weeks. After 24 weeks, 87.5% graded the game to be satisfactory. Global cognition scores improved after 24 weeks. Home-based gamified CT shows acceptable feasibility in patients with PD, and we observed preliminary indications for efficacy. Larger trials are needed to establish this efficacy.

Effectiveness of ReSET; a strategic executive treatment for executive dysfunctioning in patients with Parkinson's disease.

In this multicentre randomised controlled trial (RCT), 43 patients with Parkinson's disease (PD) were randomly allocated to either the experimental condition receiving cognitive rehabilitation including strategy training (ReSET; Strategic Executive Treatment, n = 24) or to the control condition receiving computerised repetitive practice training for attention (Cogniplus, n = 16). We expected that strategy training (ReSET) would be more effective than cognitive training (Cogniplus) in improving patients' everyday life executive functioning. Neuropsychological assessment was administered at baseline, at 2 weeks and 3-5 months post-treatment. Primary outcome measure was the Role Resumption List (RRL). Secondary outcome measures were treatment goal attainment (TGA), Dysexecutive Questionnaire (DEX), Parkinson's Disease Questionnaire (PDQ-39), Zarit Burden Interview (ZBI) and neuropsychological tests. No effects of treatment were found on the primary outcome measure and on neuropsychological tests, except for one test of attention. At 2 weeks and 3-5 months post-treatment, PD patients in both the ReSET and Cogniplus group reported a significant improvement in everyday life executive functioning, as measured with TGA and the DEX-self, with an advantage for ReSET only shortly after treatment. Given these results and that PD patients were able to adhere to these treatments despite their motor symptoms and fatigue (i.e., the drop-out rate was small), we conclude that both strategy training and cognitive training for impairments in EF might be beneficial and feasible for PD patients.

Thalamic Deep Brain Stimulation for Refractory Tourette Syndrome: Clinical Evidence for Increasing Disbalance of Therapeutic Effects and Side Effects at Long-Term Follow-Up.

OBJECTIVE: Thalamic deep brain stimulation (DBS) is effective in reducing tics in patients with refractory Tourette syndrome at the short-term. Here, we report on the long-term outcome. MATERIALS AND METHODS: Seven patients underwent bilateral DBS between 2001 and 2008. The target was the centromedian nucleus, substantia periventricularis and nucleus ventro-oralis internus cross point of the thalamus. The effect on tics and side effects were evaluated with a variable follow-up duration of 12 to 78 months. RESULTS: Patient 1 and 2 showed good tic improvements of 81.6% (60 months) and 50% (36 months), respectively. However, side effects like reducing levels of energy and visual disturbances increased. In patient 1, the target was changed to the anterior part of the internal pallidum and patient 2 switched the stimulator permanently off. Patient 3 experiences still satisfying results with a tic improvement of 88.9% (78 months). Patient 4 and 7 showed minor tic improvements of 34% (16 months) and 9% (60 months), respectively. In both patients side effects became more severe and the target was changed to the anterior part of the internal pallidum. Patient 5 showed a tic improvement of 27.5% (12 months) and went abroad for stimulation of the external globus pallidus. Patient 6 developed cerebellar atrophy. He experienced several nonstimulation related side effects and turned the stimulator off. CONCLUSIONS: There seems to be an increasing disbalance of therapeutic effects and side effects at long-term follow-up, often leading to either switching the stimulator off or new surgery with a different neuro-anatomic target.

Cognitive phenotypes in parkinson's disease differ in terms of brain-network organization and connectivity.

Cognitive deficits are common in Parkinson's disease and we suspect that dysfunctions of connected brain regions can be the source of these deficits. The aim of the present study was to investigate changes in whole-brain intrinsic functional connectivity according to differences in cognitive profiles in Parkinson's disease. 119 participants were enrolled and divided into four groups according to their cognitive phenotypes (determined by a cluster analysis): (i) 31 cognitively intact patients (G1), (ii) 31 patients with only slight mental slowing (G2), (iii) 43 patients with mild to moderate deficits mainly in executive functions (G3), (iv) 14 patients with severe deficits in all cognitive domains (G4-5). Rs-fMRI whole-brain connectivity was examined by two complementary approaches: graph theory for studying network functional organization and network-based statistics (NBS) for exploring functional connectivity amongst brain regions. After adjustment for age, duration of formal education and center of acquisition, there were significant group differences for all functional organization indexes: functional organization decreased (G1 > G2 > G3 > G4-5) as cognitive impairment worsened. Between-group differences in functional connectivity (NBS corrected, P < 0.01) mainly concerned the ventral prefrontal, parietal, temporal and occipital cortices as well as the basal ganglia. In Parkinson's disease, brain network organization is progressively disrupted as cognitive impairment worsens, with an increasing number of altered connections between brain regions. We observed reduced connectivity in highly associative areas, even in patients with only slight mental slowing. The association of slowed mental processing with loss of connectivity between highly associative areas could be an early marker of cognitive impairment in Parkinson's disease and may contribute to the detection of prodromal forms of Parkinson's disease dementia. Hum Brain Mapp 38:1604-1621, 2017. © 2016 Wiley Periodicals, Inc.

Theory of mind performance in Parkinson's disease is associated with motor and cognitive functions, but not with symptom lateralization.

Next to the typical motor signs, Parkinson's disease (PD) goes along with neuropsychiatric symptoms, amongst others affecting social cognition. Particularly, Theory of Mind (ToM) impairments have mostly been associated with right hemispherical brain dysfunction, so that it might prevail in patients with left dominant PD. Fourty-four PD patients, twenty-four with left and twenty with right dominant motor symptoms, engaged in the Reading the Mind in the Eyes (RME) and the Faux Pas Detection Test (FPD) to assess affective and cognitive ToM. The results were correlated with performance in further cognitive tests, and analyzed with respect to associations with the side of motor symptom dominance and severity of motor symptoms. No association of ToM performance with right hemispheric dysfunction was found. RME results were inversely correlated with motor symptom severity, while FPD performance was found to correlate with the performance in verbal fluency tasks and the overall cognitive evaluation. Affective ToM was found associated with motor symptom severity and cognitive ToM predominantly with executive function, but no effect of PD lateralization on this was identified. The results suggest that deficits in social cognition occur as a sequel of the general corticobasal pathology in PD, rather than as a result of hemisphere-specific dysfunction.

Objective Versus Subjective Measures of Executive Functions: Predictors of Participation and Quality of Life in Parkinson Disease?

OBJECTIVES: To determine whether objective (neuropsychological tests) and subjective measures (questionnaires) of executive functions (EFs) are associated in patients with Parkinson disease (PD), and to determine to what extent level of participation and quality of life (QoL) of patients with PD can be predicted by these measures of EFs. DESIGN: Correlational research design (case-control and prediction design). SETTING: Departments of neuropsychology of 3 medical centers. PARTICIPANTS: A sample (N=136) of patients with PD (n=42) and their relatives, and controls without PD (n=94). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A test battery measuring EFs. In addition, patients, their relatives, and controls completed the Dysexecutive Questionnaire, Brock Adaptive Functioning Questionnaire, and Barkley Deficits in Executive Functioning Scale - time management questionnaires measuring complaints about EFs. Participation and QoL were measured with the Impact on Participation and Autonomy scale and the Parkinson's Disease Questionnaire-39, respectively. RESULTS: Patients with PD showed impairments in EFs on objective tests and reported significantly more complaints about EFs than did controls without PD. No associations were found between patients' performances on objective and subjective measures of EFs. However, both objective and subjective measures predicted patients' level of participation. In addition, subjective measures of EFs predicted QoL in patients with PD. CONCLUSIONS: These findings show that objective and subjective measures of EFs are not interchangeable and that both approaches predict level of participation and QoL in patients with PD. However, within this context, sex needs to be taken into account.

The Parkin'Play study: protocol of a phase II randomized controlled trial to assess the effects of a health game on cognition in Parkinson's disease.

BACKGROUND: In Parkinson's disease (PD), cognitive impairment is an important non-motor symptom heralding the development of dementia. Effective treatments to slow down the rate of cognitive decline in PD patients with mild cognitive impairment are lacking. Here, we describe the design of the Parkin'Play study, which assesses the effects of a cognitive health game intervention on cognition in PD. METHODS/DESIGN: This study is a multicentre, phase-II, open-randomized clinical trial that aims to recruit 222 PD patients with mild cognitive impairment. Eligible patients have PD, Hoehn & Yahr stages I-III, are aged between 40 and 75 years, and have cognitive impairment but no dementia. The intervention group (n = 111) will be trained using a web-based health game targeting multiple cognitive domains. The control group (n = 111) will be placed on a waiting list. In order to increase compliance the health game adapts to the subjects' performance, is enjoyable, and can be played at home. From each group, 20 patients will undergo fMRI to test for potential functional brain changes underlying treatment. The primary outcome after 12 weeks of training is cognitive function, as assessed by a standard neuropsychological assessment battery and an online cognitive assessment. The neuropsychological assessment battery covers the following domains: executive function, memory, visual perception, visuoconstruction and language. A compound score for overall cognitive function will be calculated as the mean score of all test Z-scores based on the distribution of scores for both groups taken together. Secondary outcomes at follow-up visits up to 24 weeks include various motor and non-motor symptoms, compliance, and biological endpoints (fMRI). DISCUSSION: This study aims at evaluating whether a cognitive intervention among PD patients leads to an increased cognitive performance on targeted domains. Strengths of this study are a unique web-based health game intervention, the large sample size, a control group without intervention and innovations designed to increase compliance. TRIAL REGISTRATION: NTR5637 on 7-jan-2016.

Subthalamic nucleus high-frequency stimulation for advanced Parkinson's disease: motor and neuropsychological outcome after 10 years.

BACKGROUND: Since the introduction of subthalamic nucleus deep brain stimulation (STN DBS), many clinical studies have shown that this therapy is safe and effective in the short and medium term. Only little is known about long-term results. OBJECTIVES: To provide an analysis of motor and cognitive outcome 10 years after STN DBS. METHODS: In this observational cohort study, we report on the motor and cognitive outcome in a cohort of 26 Parkinson's disease patients who were prospectively followed up for 10 years after STN DBS surgery. RESULTS: In the early post-operative phase, improvement in the Unified Parkinson's Disease Rating Scale (UPDRS) III (10.6, p < 0.01) and IV (2.5, p < 0.01) was seen as well as a 32% reduction in levodopa equivalent dose (p < 0.01). After 5 years, a worsening of the motor performance was observed. The worsening of motor performance was mainly due to a deterioration in bradykinesia (12.4 ± 4.6, p < 0.05) and axial symptoms (6.9 ± 2.8, p < 0.01). Memory function seemed to improve in the short term, but there was a significant decline between 1 and 5 years after surgery (p < 0.01). Mood remained relatively stable during follow-up, and one third of the patients showed impulsive behaviour after surgery. CONCLUSIONS: The motor performance of patients showed deterioration over time, due to an increase in bradykinesia and axial symptoms.

The impact of deep brain stimulation of the subthalamic nucleus on facial emotion recognition in patients with Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is successful in patients with advanced Parkinson's disease (PD) but may worsen cognitive outcome, including facial emotion recognition (FER). Data-analyses on 59 consecutive PD patients with complete pre- and postoperative assessments, using a sensitive FER test, showed no changes in FER 1 year after STN-DBS surgery, both after group and individual analyses. These findings do however not exclude the impact of FER in and on itself on the outcome after STN-DBS.

Prevalence and trajectories of neuropsychological post-COVID-19 symptoms in initially hospitalized patients.

OBJECTIVE: To investigate the prevalence and trajectories of post-COVID-19 neuropsychological symptoms. DESIGN: Prospective longitudinal multicentre cohort study. SUBJECTS: A total of 205 patients initially hospitalized with SARS-CoV-2 (COVID-19). METHODS: Validated questionnaires were administered at 9 months (T1) and 15 months (T2) post-hospital discharge to assess fatigue, cognitive complaints, insomnia, anxiety, depression, and post-traumatic stress symptoms. RESULTS: Analyses included 184 out of 205 patients. Approximately 50% experienced high cognitive complaints at T1 and T2, while severe fatigue affected 52.5% at T1 and 55.6% at T2. Clinically relevant insomnia scores were observed in 25% of patients at both time-points. Clinically relevant anxiety scores were present in 18.3% at T1 and 16.7% at T2, depression in 15.0% at T1 and 18.9% at T2, and PTSD in 12.4% at T1 and 11.8% at T2. Most symptoms remained stable, with 59.2% of patients experiencing at least 1 persistent symptom. In addition, 31.5% of patients developed delayed-onset symptoms. CONCLUSION: Post-COVID-19 cognitive complaints and fatigue are highly prevalent and often persist. A subgroup develops delayed symptoms. Emotional distress is limited. Screening can help identify most patients experiencing long-term problems. Future research should determine risk factors for persistent and delayed onset symptoms.

The spectrum of cognitive disorders in Parkinson's disease: a data-driven approach.

The objective of this study was to identify different cognitive phenotypes in Parkinson's disease (PD) using a data-driven approach. A model-based cluster analysis was conducted on the neuropsychological test results of 558 PD patients from 2 European movement disorder centers (Lille, n = 403; Maastricht, n = 155). The number of clusters was determined according to their clinical relevance as well as on the basis of 3 statistical criteria: the cubic cluster criterion, the pseudo F statistic, and the total squared correlation ratio (R(2)). A factorial discriminant analysis was performed to assess the quality of the cluster's separation. Descriptive variables were used to further characterize the clusters. A 5-cluster model was considered the clinically most relevant. The 5 clusters comprised: (1) cognitively intact patients (19.39%); (2) patients without cognitive deficits but with slight mental slowing (41.29%); (3) patients with slightly impaired overall cognitive efficiency and deficits in all cognitive domains except recognition memory (12.93%); (4) patients with severe mental slowing, impaired overall cognitive efficiency, and severe cognitive impairment in all domains, including memory (23.88%); and (5) patients with very severe impairment in all cognitive domains (2.51%). Cognitively intact patients were significantly younger and had received more years of formal education. Patients in the last 3 clusters had more severe motor symptoms, longer disease duration, and more axial signs. In the last cluster, most patients were demented. Our results confirm the heterogeneity of cognitive presentations in PD, ranging from cognitively intact patients with rather high levels of performance in each cognitive domain to very severely impaired patients.

The impact of fatigue on cognitive functioning in patients with multiple sclerosis.

OBJECTIVE: To study the impact of physical and mental fatigue on cognitive complaints and cognitive performance in patients with multiple sclerosis. DESIGN: Cross-sectional study. SETTING: An outpatient neurology clinic. SUBJECTS: Eighty patients diagnosed with clinically definite multiple sclerosis. MEASURES: The subscales physical and mental fatigue of the Multidimensional Fatigue Inventory; the Hospital Anxiety and Depression Scale and the Cognitive Failure Questionnaire. Cognitive performance was assessed by an extensive neuropsychological test battery, including several tasks requiring effortful information processing. RESULTS: Both anxiety and depression and mental fatigue significantly contributed to cognitive complaints, explaining respectively about 9% and 39% of the total variance. The contribution of physical fatigue to cognitive complaints was not significant. Both physical and mental fatigue did not significantly contribute to cognitive performance in terms of mental speed, attention, memory and executive functioning. CONCLUSIONS: To refine interventions for those patients with cognitive complaints, we advise adding measurements of anxiety, depression and fatigue to their neuropsychological assessment. Fatigue permits extensive neuropsychological assessment, which is needed to detect cognitive impairment in multiple sclerosis.

Fatigue and physical disability in patients with multiple sclerosis: a structural equation modeling approach.

Although fatigue is one of the most common and disabling symptoms in patients with multiple sclerosis (MS), its pathogenesis is still poorly understood and it is difficult to treat. The aim of the current study was to test the assumptions of a cognitive-behavioral model that explains fatigue and physical disability in MS patients, by comparing this approach with a more traditional biomedical approach. Structural equation modeling was applied to a sample of 262 MS patients. Neither the cognitive-behavioral, nor the biomedical model showed an adequate fit of our data. The modification indices supported an integration of both models, which showed a better fit than those of the separate models. This final model, is notable for at least three features: (1) fatigue is associated with depression and physical disability, (2) physical disability is associated with disease severity and fatigue-related fear and avoidance behavior, and (3) catastrophic interpretations about fatigue, fueled by depression, mediated the relationship between fatigue and fatigue-related fear and avoidance behavior. Our results suggest that an integrated approach, including the modification of catastrophic thoughts about fatigue, would be beneficial in the treatment of fatigue in MS patients.