Fatigue and cognition - hormonal perspectives

Fatigue is a common complaint and considered a very challenging symptom to cope with in many different medical diseases. The assessment of fatigue is bound up with the problems of both conceptualization and definition. In addition, few studies have investigated suitable neuropsychological tests to examine fatigue and its consequences. This thesis evaluates whether neuropsychological tests can elicit cognitive fatigue. It also investigates whether specific hormones and hormone replacement therapy influence fatigue as well as cognitive performance. Study I examined and compared neuropsychological measures of cognitive fatigue with self-rated fatigue in patients with mild traumatic brain injury (mTBI). These patients scored significantly higher than controls on both self-rated and on test-derived measures of cognitive fatigue. Cognitive fatigue was best captured with a score derived from the WAIS Digit Symbol. From our findings we concluded that cognitive fatigue was independent of depression and sleep disorder. Self-rated fatigue, on the other hand, was highly correlated to depression. Study II compared the effect of combined testosterone and estrogen replacement with estrogen treatment alone on subjective and objective measures of memory in oophorectomized women. Treatment with testosterone undecanoate 40 mg and estradiol 2 mg was associated with lower performance on immediate verbal memory compared to treatment with estrogen plus placebo. All other memory functions were unaffected. Study III explored cognitive fatigue in oophorectomized women, and whether hormonal treatment regimens, as described in study II, were related to self perceived well-being, estrogen or testosterone serum levels. We found that cognitive fatigue was frequent in oophorectomized women and negatively associated to self-perceived health and positively associated to BMI. However, treatment with testosterone + estrogen or estrogen alone had no significant effect on cognitive fatigue. Study IV investigated fatigue and cognitive performance in patients with Graves’ disease (GD). As compared to controls, patients with GD scored significantly higher on self-rated fatigue and had a higher frequency on the cognitive fatigue. They also demonstrated lower performance on learning, memory, and various tests of executive functioning. Depression was associated with self-rated fatigue but not with the cognitive fatigue measure. High-free triiodothyronine (T3) levels were positively associated to better cognitive functions but negatively to self-rated everyday consequences of fatigue among the patients. In conclusion: Cognitive fatigue measure, derived from Digit Symbol, could be a useful instrument to capture fatigue. It enables us to calculate an index of cognitive fatigue where neither depression nor sleep disturbance interfere with the result. Cognitive fatigue seems to be related to BMI and self-rated health but not directly related to hormonal levels. A curvilinear relation to sex hormones and the estrogen/testosterone ratio seem more likely. Indirect hormonal imbalances could influence subtle neuronal mechanisms leading to discrete neuropsychological dysfunctions

Monthlong Intubated Patient with Life-Threatening COVID-19 and Cerebral Microbleeds Suffers Only Mild Cognitive Sequelae at 8-Month Follow-up: A Case Report.

OBJECTIVE: To elaborate on possible cognitive sequelae related to COVID-19, associated cerebrovascular injuries as well as the general consequences from intensive care. COVID-19 is known to have several, serious CNS-related consequences, but neuropsychological studies of severe COVID-19 are still rare. METHODS: M., a 45-year-old man, who survived a severe COVID-19 disease course including Acute Respiratory Distress Syndrome (ARDS), cerebral microbleeds, and 35 days of mechanical ventilation, is described. We elaborate on M's recovery and rehabilitation process from onset to the 8-month follow-up. The cognitive functions were evaluated with a comprehensive screening battery at 4 weeks after extubation and at the 8-month follow-up. RESULTS: Following extubation, M. was delirious, reported visual hallucinations, and had severe sleeping difficulties. At about 3 months after COVID-19 onset, M. showed mild to moderate deficits on tests measuring processing speed, working memory, and attention. At assessments at 8 months, M. performed better, with results above average on tests measuring learning, memory, word fluency, and visuospatial functions. Minor deficits were still found regarding logical reasoning, attention, executive functioning, and processing speed. There were no lingering psychiatric symptoms. While M. had returned to a part-time job, he was not able to resume previous work-tasks. CONCLUSION: This case-study demonstrates possible cognitive deficits after severe COVID-19 and emphasizes the need of a neuropsychological follow-up, with tests sensitive to minor deficits. The main findings of this report provide some support that the long-term prognosis for cognition in severe COVID-19 may be hopeful

Temperature dependence of the energy dissipation in dynamic force microscopy

The dissipation of energy in dynamic force microscopy is usually described in terms of an adhesion hysteresis mechanism. This mechanism should become less efficient with increasing temperature. To verify this prediction we have measured topography and dissipation data with dynamic force microscopy in the temperature range from 100 K up to 300 K. We used 3,4,9,10-perylenetetracarboxylic-dianhydride (PTCDA) grown on KBr(001), both materials exhibiting a strong dissipation signal at large frequency shifts. At room temperature, the energy dissipated into the sample (or tip) is 1.9 eV/cycle for PTCDA and 2.7 eV/cycle for KBr, respectively, and is in good agreement with an adhesion hysteresis mechanism. The energy dissipation over the PTCDA surface decreases with increasing temperature yielding a negative temperature coefficient. For the KBr substrate, we find the opposite behaviour: an increase of dissipated energy with increasing temperature. While the negative temperature coefficient in case of PTCDA agrees rather well with the adhesion hysteresis model, the positive slope found for KBr points to a hitherto unknown dissipation mechanism

Fram Strait and Greenland Sea transports, water masses, and water mass transformations 1999–2010 (and beyond)

The exchanges between the Nordic Seas and the Arctic Ocean are important for the ocean circulation and climate. Transports are here estimated using summer hydrographic data from the Greenland Sea and the Fram Strait. Geostrophic transports are computed from hydrographic sections at 75°N in the Greenland Sea and at about 79°N in the Fram Strait. Geostrophic velocities are adjusted with summer velocities derived from Argo floats, and four conservation constraints are applied to a box closed by the two sections. The estimated net volume transports are 0.8 ± 1.5 Sv southward. Net freshwater transports through the Greenland Sea section are estimated at 54 ± 20 mSv and through the Fram Strait section at 66 ± 9 mSv. Heat loss in the area between the two sections is estimated at 9 ± 12 TW. Convection depths in the Greenland Sea are estimated from observations and vary between about 200 and 2000 dbar showing no trend. Water mass properties in the Greenland Sea are affected both by convection and lateral mixing. Vertical mixing is estimated from hydrography and based on it about 1 Sv of diluted Arctic Ocean waters are estimated to enter the Greenland Sea. The properties of Atlantic, intermediate, and deep waters are studied. Deep water properties are defined using water mass triangles and are subject to decadal changes

Conformational dynamics of the human serotonin transporter during substrate and drug binding

The serotonin transporter (SERT) is responsible for re-uptake of serotonin into the presynaptic neuron and plays a key role in synaptic transmission. Here, the authors use hydrogen-deuterium exchange mass spectrometry to probe the conformational dynamics of human SERT in the absence and presence of known substrates and targeted drugs

Fatigue and Cognitive Fatigability in Mild Traumatic Brain Injury are Correlated with Altered Neural Activity during Vigilance Test Performance

IntroductionFatigue is the most frequently reported persistent symptom following a mild traumatic brain injury (mTBI), but the explanations for the persisting fatigue symptoms in mTBI remain controversial. In this study, we investigated the change of cerebral blood flow during the performance of a psychomotor vigilance task (PVT) by using pseudo-continuous arterial spin labeling (PCASL) MRI technique to better understand the relationship between fatigability and brain activity in mTBI.Material and methodsTen patients (mean age: 37.5 ± 11.2 years) with persistent complaints of fatigue after mTBI and 10 healthy controls (mean age 36.9 ± 11.0 years) were studied. Both groups completed a 20-min long PVT inside a clinical MRI scanner during simultaneous measurements of reaction time and regional cerebral blood flow (rCBF) with PCASL technique. Cognitive fatigability and neural activity during PVT were analyzed by dividing the performance and rCBF data into quintiles in addition to the assessment of self-rated fatigue before and after the PVT.ResultsThe patients showed significant fatigability during the PVT while the controls had a stable performance. The variability in performance was also significantly higher among the patients, indicating monitoring difficulty. A three-way ANOVA, modeling of the rCBF data demonstrated that there was a significant interaction effect between the subject group and performance time during PVT in a mainly frontal/thalamic network, indicating that the pattern of rCBF change for the mTBI patients differed significantly from that of healthy controls. In the mTBI patients, fatigability at the end of the PVT was related to increased rCBF in the right middle frontal gyrus, while self-rated fatigue was related to increased rCBF in left medial frontal and anterior cingulate gyri and decreases of rCBF in a frontal/thalamic network during this period.DiscussionThis study demonstrates that PCASL is a useful technique to investigate neural correlates of fatigability and fatigue in mTBI patients. Patients suffering from fatigue after mTBI used different brain networks compared to healthy controls during a vigilance task and in mTBI, there was a distinction between rCBF changes related to fatigability vs. perceived fatigue. Whether networks for fatigability and self-rated fatigue are different, needs to be investigated in future studies

The value of incorporating personally relevant stimuli into consciousness assessment with the Coma Recovery Scale – Revised: A pilot study

Objective: To explore whether the use of personally relevant stimuli, for some tasks in the Coma Recovery Scale – Revised (CRS-R), generates more responses in patients with prolonged disorders of consciousness compared with neutral stimuli. Design: Multiple single-case design. Subjects: Three patients with prolonged disorders of consciousness recruited from an inpatient department at a regional brain injury rehabilitation clinic in Stockholm, Sweden. Methods: Patients were repeatedly assessed with the CRS-R. Randomization tests (bootstrapping) were used to compare the number of responses generated by personally relevant and neutral stimuli on 5 items in the CRS-R. Results: Compared with neutral stimuli, photographs of relatives generated significantly more visual fixations. A mirror generated visual pursuit to a significantly greater extent than other self-relevant stimuli. On other items, no significant differences between neutral and personally relevant stimuli were seen. Conclusion: Personally relevant visual stimuli may minimize the risk of missing visual fixation, compared with the neutral stimuli used in the current gold standard behavioural assessment measure (CRS-R). However, due to the single-subject design this conclusion is tentative and more research is needed

Relationship between fatigue after acquired brain injury and depression, injury localization and aetiology: An explorative study in a rehabilitation setting

Objective: Fatigue after acquired brain injury may be related to the subcortico-frontal attention network. Depression is also strongly related to fatigue. This study investigates whether injury localization, diagnosis and depression are related to self-rated mental fatigue in patients with an acquired brain injury. Design: Retrospective cross-sectional cohort study. Subjects: Sixty-one patients diagnosed with stroke, subarachnoidal haemorrhage, traumatic brain injury, or brain tumour were included in the study. Methods: Patients who underwent a multidisciplinary team assessment during September 2011 to June 2012, and who were assessed with the Mental Fatigue Scale, were included in the study. Results: A significantly higher number of patients with posterior and non-specific lesions experienced fatigue compared with those with subcortical/frontal injuries. Fewer stroke patients experienced fatigue compared with the other patient groups. How-ever, after logistic regression, only depression remained as an explanatory variable for self-rated fatigue. Nevertheless, although all patients with depression were fatigued, not all fatigued patients were depressed. Conclusion: Although depression explains a high degree of fatigue after an acquired brain injury, mental fatigue after brain injury should be viewed as a condition partly separate from depression. Future extensive comparative studies are required, preferably including neuropsychological measures

A Prospective Investigation of Graves' Disease and Selenium: Thyroid Hormones, Auto-Antibodies and Self-Rated Symptoms

BACKGROUND: In Graves' thyrotoxicosis tachycardia, weight loss and mental symptoms are common. Recovery takes time and varies between patients. Treatment with methimazole reduces thyroid hormone levels. According to previous research, this reduction has been faster if selenium (Se) is added. OBJECTIVE: The objective was to investigate whether supplementing the pharmacologic treatment with Se could change the immune mechanisms, hormone levels and/or depression and anxiety. METHODS: We prospectively investigated 38 patients with initially untreated thyrotoxicosis by measuring the thyroid-stimulating hormone (TSH), free thyroxine (FT(4)), free triiodothyronine (FT(3)), thyroid receptor antibodies and thyroid peroxidase auto-antibodies before medication and at 6, 18 and 36 weeks after commencing treatment with methimazole and levo-thyroxine, with a randomized blinded oral administration of 200 µg Se/day or placebo. The selenoprotein P concentration was determined in plasma at inclusion and after 36 weeks. The patients were also assessed with questionnaires about depression, anxiety and self-rated symptoms before medication was started and after 36 weeks. RESULTS: FT(4) decreased more in the Se group at 18 weeks (14 vs. 17 pmol/l compared to the placebo group, p = 0.01) and also at 36 weeks (15 vs. 18 pmol/l, p = 0.01). The TSH increased more in the Se group at 18 weeks (0.05 vs. 0.02 mIU/l, p = 0.04). The depression and anxiety scores were similar in both groups. In the Se group, the depression rates correlated negatively with FT(3) and positively with TSH. This was not seen in the placebo group. CONCLUSIONS: Se supplementation can enhance biochemical restoration of hyperthyroidism, but whether this could shorten clinical symptoms of thyrotoxicosis and reduce mental symptoms must be investigated further