Severe fatigue and cognitive complaints are frequently reported after SARS-CoV-2 infection and may be accompanied by depressive symptoms and/or limitations in physical functioning. The long-term sequelae of COVID-19 may be influenced by biomedical, psychological, and social factors, the interplay of which is largely understudied over time. We aimed to investigate how the interplay of these factors contribute to the persistence of symptoms after COVID-19.

RECoVERED, a prospective cohort study in Amsterdam, the Netherlands, enrolled participants aged⩾16 years after SARS-CoV-2 diagnosis. We used a structural network analysis to assess relationships between biomedical (initial COVID-19 severity, inflammation markers), psychological (illness perceptions, coping, resilience), and social factors (loneliness, negative life events) and persistent symptoms 24 months after initial disease (severe fatigue, difficulty concentrating, depressive symptoms and limitations in physical functioning). Causal discovery, an explorative data-driven approach testing all possible associations and retaining the most likely model, was performed.

Data from 235/303 participants (77.6%) who completed the month 24 study visit were analysed. The structural model revealed associations between the putative factors and outcomes. The outcomes clustered together with severe fatigue as its central point. Loneliness, fear avoidance in response to symptoms, and illness perceptions were directly linked to the outcomes. Biological (inflammatory markers) and clinical (severity of initial illness) variables were connected to the outcomes only via psychological or social variables.

Our findings support a model where biomedical, psychological, and social factors contribute to the development of long-term sequelae of SARS-CoV-2 infection.

Cognitive impairment, anxiety, depression, fatigue, and dependence in instrumental activities of daily living (ADL) are common after stroke; however, little is known about how these outcomes may differ following treatment with endovascular clot retrieval (ECR), intravenous tissue plasminogen activator (t-PA), or conservative management.

Patients were recruited after acute treatment and invited to participate in an outcome assessment 90–120 days post-stroke. The assessment included a cognitive test battery and several questionnaires. The COVID-19 pandemic led to significant disruptions in recruitment and data collection, and the t-PA and conservative management groups were combined into a standard medical care (SMC) group.

Sixty-two participants were included in the study (ECR = 31, SMC = 31). Mean age was 66.5 (20–86) years, and 35 (56.5%) participants were male. Participants treated with ECR had significantly higher National Institutes of Health Stroke Scale scores at presentation and significantly lower education. After adjusting for stroke severity, premorbid intellectual ability, and age, treatment with ECR was associated with significantly better performances on measures of cognitive screening, visual working memory, and verbal learning and memory. Participants treated with ECR also experienced less fatigue and were more likely to achieve independence in basic and instrumental ADLs. Despite this, cognitive impairment and fatigue were still common among participants treated with ECR and anxiety and depression symptoms were experienced similarly by both groups.

Cognitive impairment and fatigue were less common but still prevalent following treatment with ECR. This has important practical implications for stroke rehabilitation, and routine assessment of cognition, emotion, and fatigue is recommended for all stroke survivors regardless of stroke treatment and functional outcome.

We describe a development and feasibility study of a Sitting Simple Baduanjin program for advanced cancer patients suffering from the fatigue–sleep disturbance symptom cluster. This study was to evaluate the practicality and safety of the Sitting Simple Baduanjin intervention and determine its preliminary efficacy.

This work employed a single-arm mixed-methods approach. The primary outcome measures were feasibility (i.e., recruitment, adherence, and satisfaction) and safety. Validated self-report questionnaires were used to evaluate the preliminary effects of the program, including fatigue, sleep quality, and quality of life at the 4th, 8th, and 12th weeks of the intervention. Qualitative interviews were also conducted after the program.

A total of 30 participants were enrolled, of which 23 (77%) completed the 12-week Sitting Simple Baduanjin program. The mean adherence rate was 88% and no adverse events were reported. Statistically significant improvements were observed in terms of fatigue, sleep quality, and quality of life after program completion. Four themes emerged from the qualitative interview data: (a) acceptability of the Sitting Simple Baduanjin technique, (b) perceived benefits of exercise, (c) barriers, and (d) facilitators.

The findings support the feasibility of the Sitting Simple Baduanjin program for advanced cancer patients and show promise in improving patients’ levels of the fatigue–sleep disturbance symptom cluster and quality of life.

Patients with advanced cancer present various symptoms as their disease progresses. Among these, fatigue is a frequent symptom in patients with advanced cancer and is associated with decreased quality of life (QOL). However, there are few reports regarding its association with thiamine deficiency (TD).

We report a case in which we found TD in a patient with advanced lung cancer who presented with weight loss, significant fatigue, and appeared to have a worsening general condition, for whom symptoms were dramatically improved within a short period of time by intravenous administration of thiamine.

The patient was a 76-year-old woman who had been diagnosed with lung cancer and liver metastases 6 months earlier. Due to interstitial pneumonia, she was not a candidate for chemotherapy and so palliative care was started. At 8 months after initial diagnosis, the patient complained of fatigue during a medical examination, so a blood sample was taken. A week later, she visited the hospital with a cane. She felt extremely fatigued and was unable to stand, but results from the previous blood test revealed that a TD. The fatigue disappeared 15 minutes after intravenous administration of thiamine and she was able to return home without the cane.

Fatigue is a frequent symptom in advanced cancer patients, and TD may be the underlying cause. Inclusion of TD in the differential diagnosis may contribute to improving patient QOL.

There is limited research on neurocognitive outcome and associated risk factors in long-term, adult survivors of childhood acute lymphoblastic leukemia (ALL), without treatment of cranial radiation therapy. Moreover, the impact of fatigue severity and pain interference on neurocognition has received little attention. In this cross-sectional study, we examined neurocognitive outcome and associated factors in this population.

Intellectual abilities, verbal learning/memory, processing speed, attention, and executive functions were compared to normative means/medians with one sample t tests or Wilcoxon signed-rank tests. Associations with risk factors, fatigue severity, and pain interference were analyzed with linear regressions.

Long-term, adult survivors of childhood ALL (N = 53, 51% females, mean age = 24.4 years, SD = 4.4, mean = 14.7 years post-diagnosis, SD = 3.4) demonstrated above average intellectual abilities, but performed below average in attention, inhibition, processing speed, and shifting (p < 0.001). Executive functioning complaints were significantly higher than normative means, and positively associated with fatigue (p < 0.001). There was no interaction between sex and fatigue and no neurocognitive impairments were associated with pain interference, risk group, age at diagnosis, or sex.

Long-term, adult survivors of ALL treated without cranial radiation therapy, demonstrate domain-specific performance-based neurocognitive impairments. However, continued research on the neurocognitive outcome in this population as they age will be important in the coming years. Executive functioning complaints were frequently in the clinical range, and often accompanied by fatigue. This suggests a need for cognitive rehabilitation programs.

Fatigue is a central feature of myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), but many ME/CFS patients also report comorbid pain symptoms. It remains unclear whether these symptoms are related to similar or dissociable brain networks. This study used resting-state fMRI to disentangle networks associated with fatigue and pain symptoms in ME/CFS patients, and to link changes in those networks to clinical improvements following cognitive behavioral therapy (CBT).

Relationships between pain and fatigue symptoms and cortico-cortical connectivity were assessed within ME/CFS patients at baseline (N = 72) and after CBT (N = 33) and waiting list (WL, N = 18) and compared to healthy controls (HC, N = 29). The analyses focused on four networks previously associated with pain and/or fatigue, i.e. the fronto-parietal network (FPN), premotor network (PMN), somatomotor network (SMN), and default mode network (DMN).

At baseline, variation in pain and fatigue symptoms related to partially dissociable brain networks. Fatigue was associated with higher SMN-PMN connectivity and lower SMN-DMN connectivity. Pain was associated with lower PMN-DMN connectivity. CBT improved SMN-DMN connectivity, compared to WL. Larger clinical improvements were associated with larger increases in frontal SMN-DMN connectivity. No CBT effects were observed for PMN-DMN or SMN-PMN connectivity.

These results provide insight into the dissociable neural mechanisms underlying fatigue and pain symptoms in ME/CFS and how they are affected by CBT in successfully treated patients. Further investigation of how and in whom behavioral and biomedical treatments affect these networks is warranted to improve and individualize existing or new treatments for ME/CFS.

Fatigue is common in pediatric-onset multiple sclerosis (POMS), yet causal factors and correlates of fatigue are poorly understood in this population. A 2016 review suggested an association between fatigue and emotional difficulties, sleep disturbance, and reduced quality of life in POMS. Information regarding the potential association between fatigue and cognitive challenges is limited and mixed. Through this systematic review, we searched for relationships between fatigue, cognition, and mental health.

Systematic review methodology and PRISMA guidelines were followed. Five electronic databases were searched: Ovid: Medline, Ovid: EMBASE, Ovid: PsycInfo, Web of Science and CINAHL. Search terms were specific to each database. Reference lists of included studies were also hand-searched. We included empirical studies that were published in English after 2001, included a sample with confirmed diagnoses of POMS using McDonald criteria, and measured fatigue, cognition and clinical factors including mental health outcomes. Cognition had to be assessed using a standardized assessment tool and studies must have examined associations between outcomes of interest either descriptively or by assessing bivariate or multivariate relationships. Covidence was used to complete the screening, extraction, and quality assessment. Two independent researchers (i.e., T.L.F, and/or S.D, and/or M.G) reviewed each paper included in the title and abstract screen and full text review. S.D and M.G completed the extraction and quality assessments. Conflicts at all stages were resolved by the lead author (T.L.F). The University of Adelaide JBI critical appraisal checklist for analytical cross-sectional studies was used to ensure the scientific rigor of each included study. Sample characteristics and measures of fatigue, clinical and cognitive variables were extracted. A narrative synthesis was conducted.

We identified 1025 abstracts through our initial search and retained 119 articles for full text review. One hundred and six of these studies were excluded during the full text review including six studies which did not examine the relationship between the outcomes of interest. Fifty-one additional studies were identified from hand-searching reference lists of included studies, of which 24 were retained for full text review. A total of 15 studies were extracted and analyzed. Overall, a positive relationship was found between fatigue and mental health outcomes (i.e., anxiety and depression), whereas results were mixed regarding the association between fatigue and performance-based measures of cognition as well as fatigue and other clinical characteristics (e.g., disease duration, EDSS, treatment with DMDs, relapse rate, age at disease onset). In some studies, fatigue and executive functioning performance were negatively related; the relationship was less clear in others (e.g., both fatigued and non-fatigued MS patients demonstrated cognitive challenges, an association between fatigue and executive functioning was identified at follow-up but not baseline). Eleven of the 15 included studies (73%) did not identify associations between fatigue and cognition.

While studies are mixed, fatigue in children has been associated with aspects of cognition. Understanding the relationship between fatigue, cognition, and mental health and identifying gaps in the existing literature, have implications for informing interventions for this clinical population.

Fatigue, which can be classified into physical and cognitive subtypes (Schiehser et al., 2012), is a common non-motor symptom in persons with Parkinson’s disease (PD) that has no clear treatment. Cognitive changes, also common in PD (Litvan et al., 2012), may impact how patients perceive fatigue (Kukla et al., 2021). Grit is a personality trait defined as perseverance and passion towards a long-term goal, and is associated with multiple positive outcomes such as lower fatigue levels in healthy individuals (Martinez-Moreno et al., 2021). However, scarce research has examined the relationship between grit and fatigue in persons with PD. Therefore, we aimed to investigate the relationship between fatigue (cognitive and physical) and grit, as well as the impact of cognitive status (i.e., cognitive normal vs. mild cognitive impairment [MCI]) on this relationship in non-demented individuals with PD.

Participants were 70 non-demented individuals with PD who were diagnosed as either cognitively normal (n=20) or MCI (n=50) based on Level II of the Movement Disorder Society PD-MCI criteria. Participants completed the Modified Fatigue Impact Scale (MFIS), which consists of two subscales (cognitive and physical fatigue) that are combined for a total overall fatigue score. Participants also completed the Grit Scale, which consists of items such as ambition, perseverance, and consistency. ANOVAs were conducted to determine differences in grit between PD-cognitively normal vs PD-MCI groups. Correlations and multiple hierarchical regressions controlling for significant demographics (i.e., age, education, sex), mood (i.e., depression, anxiety) and disease variables (i.e., disease duration, Levodopa equivalent dosage) with backwards elimination were conducted to evaluate the relationship between grit and fatigue (MFIS total score and MFIS cognitive and physical fatigue subscales).

There was no significant difference in grit total scores between PD patients who were cognitively normal or MCI (p = .336). Higher grit total scores predicted lower MFIS total (ß = -.290, p = .005) and lower cognitive fatigue (ß = -.336, p < .001) scores in the total sample, above and beyond relevant covariates as well as cognitive status. Grit scores were not significantly associated with physical fatigue (ß = -.206, p = .066). Furthermore, cognitive status was not a significant predictor of fatigue scores in any of the models (all p’s > .28).

Findings indicate that higher levels of grit are associated with lower levels of fatigue, specifically cognitive fatigue, in individuals with PD. These results held true for those who were cognitively normal or with MCI, suggesting that grit may impact fatigue in non-demented PD patients regardless of cognitive status. These findings underscore the importance of considering grit when assessing or treating fatigue, particularly cognitive fatigue, in persons with PD.

Patients with Post-Acute COVID Syndrome (PACS) are reported to commonly experience a variety of cognitive, physical, and neuropsychiatric symptoms well beyond the acute phase of the illness. Notably, concerns involving mood, fatigue, and physical symptoms (e.g., pain, headaches) following COVID-19 appears to be especially prevalent. It is unclear, however, the extent to which such symptoms are associated with cognitive problems in patients with PACS. In the present study, we examined the prevalence of cognitive impairment in a sample of patients with PACS, as well as the relationship between cognitive functioning and several non-cognitive symptoms.

Participants were 38 patients with PACS [71.1% female; mean age = 48.03 years (SD = 11.60) and years of education = 15.26 years (SD = 2.60)] seen for a neuropsychological evaluation at a large Northeastern medical center at least three months from the time of COVID-19 diagnosis (per PCR test). As part of a larger battery, patients completed the Hopkins Verbal Learning Test- Revised (HVLT, learning and delayed recall), Trail Making Test (TMT; time to complete parts A and B), Controlled Oral Word Association Test (COWAT total correct), and Animals (total correct). They also were administered the Chalder Fatigue Scale-11 (CFS-11), Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and Patient Health Questionnaire (PHQ-15). The percentage of patients with scores in the impaired range (z < -1.5) on cognitive tests was determined. Correlations between cognitive and non-cognitive measures were also examined.

The most frequent impairment was seen for COWAT (21.2%), followed by TMT-A and TMT-B (both 13.9%), then category fluency (9.1%). No patients were impaired on HVLT-R Learning and only one (4%) for HVLT-R Delayed Recall. Overall, the sample endorsed considerable depression, anxiety, fatigue, as well as physical symptoms. Greater fatigue was associated with worse verbal learning, processing speed, cognitive flexibility, and verbal fluency (letter and category). Worse physical symptom severity was related to poorer verbal delayed recall and cognitive flexibility. Greater anxiety was also associated with worse cognitive flexibility, while more severe depression was related to poorer category fluency.

In our sample of patients with PACS, seen for evaluation several months since contracting COVID-19, phonemic fluency was the most common cognitive impairment, though less than a quarter were impaired on any given cognitive test. Importantly, several associations were observed between cognitive test performance and non-cognitive symptoms commonly endorsed by patients with PACS. These findings highlight the importance of assessing multiple factors potentially contributing to cognitive impairment in these patients. Interventions designed to address such symptoms may be helpful in ameliorating cognitive functioning in those with PACS.

Cognitive fatigue (CF) is a common, yet poorly understood symptom in neurological disorders (e.g., multiple sclerosis, Parkinson’s disease, stroke). Studies show that reward plays a central role in CF. For instance, introducing or increasing reward often improves task performance. It is less clear, however, how reward affects subjective (self-reported) CF (SCF). This study examined the effect of reward type (monetary or performance feedback) and frequency (infrequent or frequent) on SF.

In an online between-subjects study, 400 participants completed a computerized cognitive switching task and were randomly grouped into one of the five possible groups based on reward condition: [1] infrequent monetary reward, [2] frequent monetary reward, [3] infrequent performancefeedback reward, [4] frequent performance feedback reward, and [5] a no-reward group. SCF was assessed using the Visual Analog Scale of Fatigue (VAS-F) during the task. Mixed effects models were used to estimate the influence of reward type and frequency on task performance and SCF.

We found that the monetary groups were significantly faster (p<.001) compared to the feedback and no-reward groups, and that the frequent group was faster (p=.05) compared to the infrequent group. Reward type and frequency did not have a significant effect on VAS-F scores. However, when we looked at each reward group, we found that the monetary-infrequent reward group was associated with a decrease in VAS-F scores on average compared to the no-reward group (p=.04).

The type and frequency of reward influence aspects of task performance (response time but not accuracy). Findings suggest that money had a greater effect on response time and may decrease SCF in cognitively healthy individuals when provided infrequently. Future studies should examine how these findings translate to clinical populations. Continued work is needed to understand how and which specific behavioral reward manipulations reduce fatigue, which could eventually lead to improved assessment and our ability to target fatigue across clinical populations.

The post-COVID-19 condition describes the persistence or onset of somatic symptoms (e.g. fatigue) after acute COVID-19. Based on an existing cognitive-behavioral treatment protocol, we developed a specialized group intervention for individuals with post-COVID-19 condition. The present study examines the feasibility, acceptance, and effectiveness of the program for inpatients in a neurological rehabilitation setting.

The treatment program comprises eight sessions and includes psychoeducational and experience-based interventions on common psychophysiological mechanisms of persistent somatic symptoms. A feasibility trial was conducted using a one-group design in a naturalistic setting. N = 64 inpatients with a history of mild COVID-19 that fulfilled WHO criteria for post-COVID-19 condition were enrolled. After each session, evaluation forms were completed and psychometric questionnaires on somatic and psychopathological symptom burden were collected pre- and post-intervention.

The treatment program was well received by participants and therapists. Each session was rated as comprehensible and overall satisfaction with the sessions was high. Pre-post effect sizes (of standard rehabilitation incl. new treatment program; intention-to-treat) showed significantly reduced subjective fatigue (p < 0.05, dav = 0.33) and improved disease coping (ps < 0.05, dav = 0.33–0.49).

Our results support the feasibility and acceptance of the newly developed cognitive-behavioral group intervention for individuals with post-COVID-19 condition. Yet, findings have to be interpreted cautiously due to the lack of a control group and follow-up measurement, the small sample size, and a relatively high drop-out rate.

Autonomic nervous system (ANS) dysregulation might be relevant to the pathophysiology of fatigue and cognitive impairment in depression and perhaps should be considered when making prescribing decisions.

To determine the relationship of self-reported ANS symptoms with fatigue, cognition and prescribed medication in people with a diagnosis of depression, in comparators without depression but with other mental health, neurodevelopmental or neurodegenerative disorders (active controls) and in healthy controls.

Cross-sectional analysis of an opportunistic sample from England. Self-reported data were collected on demographics, diagnosis, medication, ANS symptoms (Composite Autonomic Symptom Scale-31, COMPASS-31) and fatigue (Visual Analogue Scale for Fatigue, VAS-F). A subsample completed cognitive tests (THINC-it), including the subjective Perceived Deficits Questionnaire five-item version (PDQ-5). Spearman's correlation and mediation models were used to explore the relationship between COMPASS-31, VAS-F and PDQ-5 scores.

Data were obtained for 3345 participants, 22% with depression. The depression group had significantly (P < 0.01) more severe autonomic dysregulation as measured by COMPASS-31 scores (median 30) than active (median 23) and healthy controls (median 10). The depression group had significantly higher symptom severity (P < 0.01) than both control groups on the VAS-F and PDQ-5. Overall, there was a significantly positive correlation (P < 0.01) between COMPASS-31, VAS-F scores (Spearman's rho rs = 0.44) and PDQ-5 scores (rs = 0.56). COMPASS-31 scores mediated greater symptom severity on the VAS-F and PDQ-5 for those with depression. COMPASS-31 scores remained significantly different between the depression group and both control groups independently of medication.

People with a diagnosis of depression report worse fatigue and cognition than active and healthy comparators; this appears to be mediated by ANS dysregulation.