Effect of estrogen and testosterone replacement therapy on cognitive fatigue.

Both estrogen and testosterone insufficiency has been associated with reduced psychological well-being including fatigue. However, hormonal replacement studies on fatigue are rare. Therefore, we wanted to study the effect of testosterone and estrogen replacement therapy on cognitive fatigue and the relation between sex hormone levels and cognitive fatigue in oophorectomized women. Fifty women with surgically induced menopause (mean age: 54.0 ± 2.9 years) were randomly assigned to treatment with estradiol valerate in combination with testosterone undecanoate or placebo for 24 weeks in a double-blind cross-over study. Neuropsychological tests and questionnaires were used to assess cognitive fatigue and psychological well-being. Cognitive fatigue was significantly associated to poor self-rated health and higher body mass index but not to general psychological well-being or sex hormone levels. Treatment with testosterone + estrogen had no significant effect on cognitive fatigue but the results indicated a curvilinear relation for hormonal levels. The estrogen/testosterone ratio was more related to functions rather than high or low hormone levels per se. We found that cognitive fatigue is frequent in oophorectomized women and negatively associated to self-perceived health and positively associated to BMI. A well-balanced ratio between estrogen and testosterone levels may be important for cognitive fatigue.

Post mTBI fatigue is associated with abnormal brain functional connectivity.

This study set out to investigate the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants' fatigue levels and conducted resting-state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject's fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self-reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system.

An investigation of attention, executive, and psychomotor aspects of cognitive fatigability.

OBJECTIVE: Self-perceived mental fatigue is a common presenting symptom in many neurological diseases. Discriminating objective fatigability from self-perceived mental fatigue might facilitate neuropsychological diagnosis and treatment programs. However clinically valid neuropsychological instruments suitable for assessment of fatigability are still lacking. The prime aim of the study was to investigate aspects of cognitive fatigability and to identify properties of neuropsychological tests suitable to assess fatigability in patients with persistent cognitive complaints after mild brain injury. Another aim was to investigate whether cognitive fatigability captured by neuropsychological measures is influenced by depression or sleep disturbances. METHOD: Twenty-four patients with persistent cognitive symptoms after mild traumatic brain injury (mTBI), (aged 18-51 years) and 31 healthy controls (aged 20-49 years) underwent neuropsychological testing measuring three cognitive fatigability domains: Attention fatigability was assessed using the Ruff 2 & 7 Selective Attention Test, executive fatigability using the Color Word Test (Stroop), and psychomotor fatigability using the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III). Subjective fatigue was measured using the Fatigue Severity Scale and a questionnaire of everyday consequences of fatigue. Depression was screened using the Hospital Anxiety and Depression Scale and sleep disturbances using the Pittsburgh Sleep Quality Index. RESULTS: The patients reported significantly more mental fatigue and performed worse on tests of psychomotor and executive fatigability than the healthy controls. Furthermore, the cognitive fatigability measures were not influenced by depression or sleep disturbances, as was the case in self-reported fatigue. CONCLUSION: Tests demanding executive or simultaneous processing of several neuropsychological functions seem most sensitive in order to capture cognitive fatigability. Clinical tests that can capture fatigability enable a deeper understanding of how fatigability might contribute to cognitive complaints and problems in maintaining daily activities.