Olfaction is a sense involved in a complex set of tasks, influencing eating behavior, increasing awareness of environmental hazards and affecting social communication. Surprisingly, smell disorders are very frequent, especially in the elderly population. Several recent studies conducted mostly in older subjects have demonstrated a strong association between olfactory impairment and overall mortality risk, with anosmia being even more predictive of 5 years mortality risk than cardiovascular disease. Presently, the underlying pathophysiology linking olfactory impairment to mortality remains unknown and only putative mechanisms are suggested. This review aims to examine the link between olfactory impairment and mortality and to discuss existing ideas on underlying existing mechanisms including, (1) the effect of olfactory loss on nutrition, life-threatening situations and social interactions, (2) associated neurodegenerative diseases, (3) accelerated brain aging, and (4) reflection of general health status being reflected in olfactory function.

Th1 cytokine-induced down-regulation of Cav-1 could be responsible for intracytoplasmic T4 synthesis and mislocalization of DUOX and TPO, suggesting an important role for Cav-1 in the preservation of thyroxisome integrity. The thyroxisome's disruption, leading to uncontrolled OS and cell apoptosis, is a key, event in HT pathogenesis.

Even when TSHR-Ab level is normalized, OS and antioxidant protein expression is high in EOM muscular cells and adipocytes in GO compared with controls. This justifies a supplementation with antioxidants in active as well as chronic GO patients. Orbital muscular cells are also the sources of PPARγ and ApN, which have direct or indirect local protective effects against OS. Modulation of these proteins could be considered as a future therapeutic approach for GO.

PPARγ may play a central role in normal thyroid physiology by upregulating Cav-1, essential for the organization of the thyroxisome and extracellular iodination. By upregulating catalase, PPARγ may also contribute to cell homeostasis. The inhibitory effect of Th1 cytokines on PPARγ expression may be considered as a new pathogenetic mechanism for HT, and the use of PPARγ agonists could open a new therapeutic approach.

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Objectives Frailty has been suggested to take part in the recently demonstrated link between olfactory dysfunction and overall mortality risk. Preoperative assessment of frailty is essential to detect the most vulnerable patients scheduled for surgery. The aim of this study was to evaluate whether olfactory dysfunction is a reliable predictor of preoperative frailty and postoperative outcome. Design This was a single-center prospective observational study conducted between July and October 2020 in Brussels, Belgium. Setting And Participants 155 preoperative patients aged from 65 years old and scheduled for elective non-cardiac surgery. Measurements Olfactory function was examined using the Sniffin’ Sticks 12-item identification test. Frailty was assessed using the Edmonton Frail Scale (EFS) and handgrip strength. The clock drawing test (CDT) from the EFS was also analyzed separately to evaluate cognitive function. Patients were followed for postoperative complications and mortality over one year. Results Olfactory dysfunction was significantly associated with the EFS score, anosmic patients having a higher median EFS score than normosmic patients (6[4–7] vs 4[2–5], p =.025). Anosmic patients had an increased odds of being frail after adjusting for possible confounding factors (OR: 6.19, 95% CI: 1.65–23.20, p =.007) and were more at risk of poor postoperative outcome (including complications and death) (OR: 4.33, 95% CI: 1.28–14.67, p =.018). Conclusions Olfactory dysfunction is associated with preoperative frailty determined by the EFS and with poor post-surgical outcome at one-year.

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Purpose of Review The aim was to synthesize key findings regarding the use of functional MRI (fMRI) to assess olfactory dysfunction (OD), and thus, to evaluate whether fMRI could be a reliable clinical diagnostic tool. Recent Findings In response to olfactory stimulation, patients with quantitative OD display reduced activation in olfactory-related brain regions but also stronger activation in non-olfactory brain areas. Parosmic patients also seem to show both weaker and higher brain signals. As to trigeminal chemosensory system, fMRI suggests that central processing may be declined in patients with OD. Functional connectivity studies report a possible correlation between altered neuronal connections within brain networks and olfactory performances. Summary fMRI emerges as a valuable and promising objective method in OD evaluation. Yet, its high inter-individual variability still precludes its routine clinical use for diagnostic purpose. Future research should focus on optimizing stimulation paradigms and analysis methods.