COVID-19 pandemic brought chemosensory impairment to the forefront of medicine, revealing gaps in the knowledge of pathophysiological mechanisms, true prevalence and preventive/therapeutic alternatives. This is a sub-study of the ORCHESTRA cohort focusing on post-COVID-19 chemosensory symptoms. Risk factors for neurosensorial cluster of post-COVID-19 syndrome (NSc-PCS) were assessed through multivariable analysis. Psychophysical validated tests were applied on a sub-population of 50 patients. Qualitative chemosensory symptoms as well as nasal and oral chemesthesis were evaluated through anamnestic interview and the quality of life through the SF-36 questionnaire. Chemosensory symptoms evolution and olfactory training\'s outcome were assessed through phone-call interviews. Out of 1187 patients (female, N = 630), 550 (47%) presented NSc-PCS, with a lower risk for older age and monoclonal antibodies treatment, and a higher risk in females (p < 0.001). Out of the 50 patients evaluated with psychophysical tests, 66% showed smell reduction with a qualitative alteration in 50% of hyposmic and 35% of normosmic patients. Hypogeusia was present in 14 (28%) of the patients assessed, with 56% showing a qualitative alteration; 53% of normogeusic patients presented qualitative disorders. NSc-PCS has a complex, fluctuating, multifaceted presentation. Quantifying and characterizing COVID-19-related chemosensory impairment is key to understand underlying mechanisms and to develop preventive and therapeutic treatment.

OBJECTIVE: Smell and taste are senses that contribute to a child\'s overall well-being. Disorders affecting these senses can impact a child\'s daily life from enjoying meals to detecting potential dangers through scent. The aim of this study is to describe patient characteristics and etiological causes of olfactory (OD) and/or gustatory disorders (GD) in children referred to a smell and taste clinic. Secondly, we aim to suggest a clinical work up.
METHODS: Retrospective study where data were collected from 57 children who were referred consecutively to the University Clinic for Flavour, Balance, and Sleep; Department of Otorhinolaryngology (ORL), Head and Neck Surgery; Goedstrup Hospital, Denmark, for assessment due to OD/GD from January 2017 to May 2023.
RESULTS: Most of the children had anosmia (60 %), whereas sensation of the basic tastes was intact in all but eight children (16 %). The lowest TDI scores were in children with congenital OD. The underlying etiology was congenital followed by postinfectious mostly related to Covid-19. Picky eating including anorectic traits were seen in 16 % of patients.
CONCLUSIONS: The focus on smell loss in pediatric population is low, and probably does not adequately reflect either underlying prevalence in this group or the possible consequences on a child\'s well-being. Moreover, increased awareness of children\'s smell and taste loss is needed, as it may be associated with eating disturbances.

BACKGROUND: Intranasal trigeminal function is important in detecting environmental stimuli. The impact of age-associated chemosensory dysfunction upon taste and olfaction is well described, but an understanding of trigeminal loss (chemesthesis) is lacking.
OBJECTIVE: The goal of this study was to characterize trigeminal function in a cohort of older adults and explore potential impacts.
METHODS: Twenty-eight participants over 50 years of age were recruited from the community as part of an aging cohort study. This nested cohort completed chemosensory questionnaires, patient-reported outcome measures (PROMs), and psychophysical testing for taste (taste strips), olfaction (Sniffin\' Sticks), and trigeminal function (eucalyptol lateralization). Data were analyzed for associations between trigeminal function, olfactory, and taste psychophysical performance, patient-reported metrics, and demographic risk factors.
RESULTS: Patient-reported trigeminal impairment is less severe than other chemosensory loss, with mean visual analog scores (VAS, rated 0-100 from least to most severe) for smell (32.9 ± 34.2), taste (20.6 ± 28.4), and trigeminal sensation (9.5 ± 12.8). Despite low VAS scores, psychophysical trigeminal dysfunction was present in 10 (35.7%) subjects. Psychophysical olfactory and taste dysfunction were present in 16 (57.1%) and eight (28.6%) participants respectively. Hypercholesterolemia was associated with psychophysical trigeminal dysfunction (mean lateralization performance in hypercholesterolemia 57.7% ± 17.1 vs. 74.1% ± 10.4, p = .008).
CONCLUSIONS: Intranasal trigeminal impairment is present in nearly one-third of aging adults when assessed by psychophysical methods but is under-recognized. Hyperlipidemia may be associated with trigeminal impairment. Future inquiries should better characterize these findings in larger and prospective cohorts.

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Olfactory dysfunction, influenced by factors such as aging and environmental stress, is linked to various neurological disorders. The olfactory bulb\'s connections to brain areas like the hypothalamus, piriform cortex, entorhinal cortex, and limbic system make olfactory dysfunction a contributor to a range of neuropathological conditions. Recent research has underscored that olfactory deficits are prevalent in individuals with both metabolic syndrome and dementia. These systemic metabolic alterations correlate with olfactory impairments, potentially affecting brain regions associated with the olfactory bulb. In cases of metabolic syndrome, phenomena such as insulin resistance and disrupted glucose metabolism may result in compromised olfactory function, leading to multiple neurological issues. This review synthesizes key findings on the interplay between metabolic-induced olfactory dysfunction and neuropathology. It emphasizes the critical role of olfactory assessment in diagnosing and managing neurological diseases related to metabolic syndrome.

Olfactory functioning involves multiple cognitive processes and the coordinated actions of various neural systems. Any disruption at any stage of this process may result in olfactory dysfunction, which is consequently widely used to predict the onset and progression of diseases, such as Alzheimer\'s Disease (AD). Although the underlying mechanisms have not yet been fully unraveled, apparent changes were observed in olfactory brain areas form patients who suffer from AD by means of medical imaging and electroencephalography (EEG). Olfactory dysfunction holds significant promise in detecting AD during the preclinical stage preceding mild cognitive impairment (MCI). Owing to the strong specificity, olfactory tests are prevalently applied for screening in community cohorts. And combining olfactory tests with other biomarkers may further establish an optimal model for AD prediction in studies of specific olfactory dysfunctions and improve the sensitivity and specificity of early AD diagnosis.

Olfactory dysfunction is a common non-motor symptom of Parkinson\'s disease(PD) and may hold valuable insights into the disease\'s underlying pathophysiology. This study aimed to investigate cortical morphometry alterations in PD patients with severe hyposmia(PD-SH) and mild hyposmia(PD-MH) using surface-based morphometry(SBM) methods. Participants included 36 PD-SH patients, 38 PD-MH patients, and 40 healthy controls(HCs). SBM analysis revealed distinct patterns of cortical alterations in PD-SH and PD-MH patients. PD-MH patients exhibited reduced cortical thickness in the right supramarginal gyrus, while PD-SH patients showed widespread cortical thinning in regions including the bilateral pericalcarine cortex, bilateral lingual gyrus, left inferior parietal cortex, left lateral occipital cortex, right pars triangularis, right cuneus, and right superior parietal cortex. Moreover, PD-SH patients displayed reduced cortical thickness in the right precuneus compared to PD-MH patients. Fractal dimension analysis indicated increased cortical complexity in PD-MH patients\' right superior temporal cortex and right supramarginal gyrus, as well as decreased complexity in the bilateral postcentral cortex, left superior parietal cortex, and right precentral cortex. Similarly, cortical gyrification index and cortical sulcal depth exhibited heterogeneous patterns of changes in PD-SH and PD-MH patients compared to HCs. These findings underscore the multifaceted nature of olfactory impairment in PD, with distinct patterns of cortical morphometry alterations associated with different degrees of hyposmia. The observed discrepancies in brain regions showing alterations reflect the complexity of PD\'s pathophysiology. These insights contribute to a deeper understanding of olfactory dysfunction in PD and provide potential avenues for early diagnosis and targeted interventions.

Rationale: Adult neurogenesis in the subventricular zone (SVZ) is essential for maintaining neural homeostasis, and its dysregulation contributes to anosmia and delayed tissue healing in neurological disorders, such as Parkinson\'s disease (PD). Despite intricate regulatory networks identified in SVZ neurogenesis, the molecular mechanisms dynamically maintaining neural stem/progenitor cells (NSPCs) in response to physiological and pathological stimuli remain incompletely elucidated. Methods: We generated an RNA binding motif protein 24 (Rbm24) knockout model to investigate its impact on adult neurogenesis in the SVZ, employing immunofluorescence, immunoblot, electrophysiology, RNA-sequencing, and in vitro experiments. Further investigations utilized a PD mouse model, along with genetic and pharmacological manipulations, to elucidate Rbm24 involvement in PD pathology. Results: Rbm24, a multifaceted post-transcriptional regulator of cellular homeostasis, exhibited broad expression in the SVZ from development to aging. Deletion of Rbm24 significantly impaired NSPC proliferation in the adult SVZ, ultimately resulting in collapsed neurogenesis in the olfactory bulb. Notably, Rbm24 played a specific role in maintaining Notch1 mRNA stability in adult NSPCs. The Rbm24/Notch1 signaling axis was significantly downregulated in the SVZ of PD mice. Remarkably, overexpression of Rbm24 rescued disruption of adult neurogenesis and olfactory dysfunction in PD mice, and these effects were hindered by DAPT, a potent inhibitor of Notch1. Conclusions: Our findings highlight the critical role of the Rbm24/Notch1 signaling axis in regulating adult SVZ neurogenesis under physiological and pathological circumstances. This provides valuable insights into the dynamic regulation of NSPC homeostasis and offers a potential targeted intervention for PD and related neurological disorders.

BACKGROUND: Olfactory dysfunction has been reported for its association with cognitive impairment and incident dementia. However, the underlying role of neurodegeneration in this relationship is not fully understood.
METHODS: This prospective cohort study included participants from the Shanghai Aging Study (SAS) who were 60 years or older and diagnosed as dementia-free at baseline and completed at least one follow-up interview between 2010 and 2022. At baseline, olfactory identification function was assessed by the 12-item Sniffin\' Sticks Smell test (SSST-12). Olfactory dysfunction was defined as SSST-12 < 7, 6, and 5 in three age groups of participants with (age < 70, 70 ≤ age < 80, and age ≥ 80), respectively, according to previously reported normative data of olfaction in the SAS. Baseline blood Neurofilament Light Chain (NfL) was quantified using the ultra-sensitive Single Molecular Array technology (Quanterix), and dichotomized into low and high levels according to the median concentration. Multiple cognitive function assessments were administered by the Mini-mental State Examination (MMSE) at baseline and follow-ups. We used the linear mixed-effect model to fit the MMSE trajectories in participants with and without olfactory dysfunction adjusting for baseline age, sex, education year, smoking, and APOE ε4, with person-specific MMSE intercept and slope. Stratified analysis was conducted in participants with low and high NfL.
RESULTS: Among 1125 participants included in this study, 296 were defined as having olfactory dysfunction at baseline. Less education, higher proportion of APOE ε4 allele, and lower baseline and follow-up MMSE scores were observed in participants with olfactory dysfunction (Table 1). During the median 9.4 years follow-up, participants with olfactory dysfunction at baseline evidenced a faster MMSE decline compared with those without olfactory dysfunction (b [95% CI]: -0.08 [-0.15, -0.02], P = 0.02) (Figure 1). Such association remained statistically significant (-0.18 [-0.31, -0.06], P = 0.005) in the subgroup with high NfL, but not in the subgroup with low NfL (0.004 [-0.07, 0.07], P = 0.92) (Figure 2).
CONCLUSIONS: Blood NfL may modify the association of olfactory dysfunction with long-term cognitive decline in community-dwelling older adults. In individuals with high potential neurodegeneration, olfactory dysfunction may be an independent indicator of future cognitive deterioration.