Introduction Fatigue is a prevalent and potentially debilitating symptom that impacts the health-related quality-of-life of individuals diagnosed with acute and chronic medical conditions. Yet, its etiologic mechanism is not fully understood. Additionally, the assessment and determination of the clinical meaning of fatigue and its multidimensionality may vary by medical condition. Methods A scoping literature review was conducted to investigate how fatigue is defined and measured, including its dimensions, in non-oncologic medical conditions. The PubMed database was searched using keywords. Results Overall, 8376 articles were screened at the title/abstract levels, where 293 articles were chosen for full-text review that mentioned fatigue or included fatigue measures. The review of the full text excluded 246 articles that did not assess at least one fatigue dimension using validated questionnaires and clinical tests. The final set included 47 articles. Physical fatigue was the most assessed fatigue dimension and the Multidimensional Fatigue Inventory was the most widely used questionnaire to assess fatigue in this review. Limitations This review was limited by including only English-language publications and using PubMed as the sole database for the search. Conclusions This review affirms that fatigue is a multidimensional construct, agnostic of medical condition, and that individual fatigue dimensions can be measured by validated clinical measures. Future research should focus on expanding the repertoire of clinical measures to assess specific fatigue dimensions.

combined androgen deprivation therapy (AdT) and radiation therapy (RT) is the standard of care treatment for non-metastatic prostate cancer (NMPC). Despite the efficacy, treatment-related symptoms including fatigue greatly reduce the quality of life of cancer patients. The goal of the study is to examine the influence of combined ADT/RT on fatigue and understand its underlying mechanisms. A total of 64 participants with NMPc were enrolled. Fatigue was assessed using the Functional Assessment of cancer Therapy-Fatigue. Mitochondrial function parameters were measured as oxygen consumption from peripheral blood mononuclear cells (PBMcs) extracted from participants' whole blood. An AdT/RT-induced fatigue mouse model was developed, with fatigue measured as a reduction in voluntary wheel-running activity (VWRA) in 54 mice. Mitochondrial function was assessed in the AdT/RT mouse brains using western blot analysis of glucose transporter 4 (GLUT4) and transcription factor A, mitochondrial (TFAM). The results demonstrated that fatigue in the AdT group was exacerbated during RT compared with the non-ADT group. This effect was specific to fatigue, as depressive symptoms were unaffected. PBMcs of fatigued subjects exhibited decreased ATP coupling efficiency compared to non-fatigued subjects, indicative of mitochondrial dysfunction. The AdT/RT mice demonstrated the synergistic effect of AdT and RT in decreasing VWRA. Brain tissues of AdT/RT mice exhibited decreased levels of GLUT4 and TFAM suggesting that impaired neuronal metabolic homeostasis may contribute to fatigue pathogenesis. In conclusion, these findings suggest that fatigue induced by ADT/RT may be attributable to mitochondrial dysfunction both peripherally and in the central nervous system (cNS). The synergistic effect of AdT/RT is behaviorally reproducible in a mouse model and its mechanism may be related to bioenergetics in the cNS.

Background Cancer‐related fatigue (CRF) is a debilitating symptom frequently reported by patients during and after treatment for cancer. CRF is a multidimensional experience and is often solely assessed by self‐report measures. The goal of the study is to examine the physical and cognitive aspects of self‐reported CRF using a cognitive function test and a physical fatigue index in order to provide objective measures that can characterize the CRF phenotype. Methods A total of 59 subjects with nonmetastatic prostate cancer receiving external beam radiation therapy were included in the study. Fatigue was measured using the Functional Assessment of Cancer Therapy‐Fatigue (FACT‐F) questionnaire. Cognitive characteristics of CRF was measured using the Stroop Color‐Word Interference computerized test and the motor aspect of fatigue was measured using the static fatigue test using a handgrip dynamometer. Findings Functional Assessment of Cancer Therapy‐Fatigue scores significantly correlated with the Stroop Interference score, but not performance accuracy in all test conditions. Fatigued subjects exhibited a more rapid decline to 50% of maximal strength and increased static fatigue index in the handgrip test, whereas maximal grip strength was not affected. Conclusions The results suggest that CRF exhibits both cognitive and physical characteristics. Subjective fatigue was associated with increased time required to overcome cognitive interference, but not cognitive performance accuracy. Fatigued patients exhibited decreased physical endurance and the ability to sustain maximal strength over time. These objective measures may serve as valuable tools for clinicians to detect cognitive and physical impairment associated with CRF.