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Sensitive smell discrimination is based on structural plasticity of the olfactory bulb,which depends on migration and integration of newborn neurons from the subventricular zone.In this study,we examined the relationship between neural stem cell status in the subventricular zone and olfactory function in rats with diabetes mellitus.Streptozotocin was injected through the femoral vein to induce type 1 diabetes mellitus in Sprague-Dawley rats.Two months after injection,olfactory sensitivity was decreased in diabetic rats.Meanwhile,the number of Brd U-positive and Brd U＋/DCX＋double-labeled cells was lower in the subventricular zone of diabetic rats compared with agematched normal rats.Western blot results revealed downregulated expression of insulin receptorβ,phosphorylated glycogen synthase kinase 3β,and β-catenin in the subventricular zone of diabetic rats.Altogether,these results indicate that diabetes mellitus causes insulin deficiency,which negatively regulates glycogen synthase kinase 3β and enhances β-catenin degradation,with these changes inhibiting neural stem cell proliferation.Further,these signaling pathways affect proliferation and differentiation of neural stem cells in the subventricular zone.Dysfunction of subventricular zone neural stem cells causes a decline in olfactory bulb structural plasticity and impairs olfactory sensitivity in diabetic rats.

Olfactory function, and specifically semantic olfactory memory (i.e., odor identification), has frequently been shown to predict cognitive functioning across multiple domains in old age. This observation suggests that olfactory function can serve as a marker for the integrity of temporolimbic cortical networks, but a clear delineation of this association is still missing. To address this issue, the present study employed voxel-based morphometry in a region of interest-based design to determine the extent to which gray matter volumes of core olfactory and memory areas are associated with olfactory memory performance in an aging population free from neurodegenerative disease. We further aimed to determine potential overlap in structural anatomical correlates, and differences in association strength, for semantic and episodic olfactory memory. Structural magnetic resonance imaging (MRI), episodic and semantic odor memory and episodic and semantic verbal memory data were collected in 422 participants from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), all aged ​≥ ​60 years. Controlling for age and education, semantic, but not episodic, olfactory memory was positively related to gray matter volume in a cluster extending from the anterior hippocampus and amygdala into the posterior piriform cortex. The observed associations remained even when verbal memory performance was controlled for, supporting a link between the olfactory memory domain and cortical volume over and above more generalized memory abilities. As such, our data provide evidence for distinct functional-structural associations for semantic odor memory, supporting the idea of temporolimbic integrity as a neurobiological substrate linking olfactory function to cognitive health in old age. •Olfactory semantic memory performance was linked to frontotemporal gray matter volume.•Associations remained significant when verbal memory performance was controlled for.•No significant correlates of olfactory episodic memory were found.

Purpose Study the efficacy of olfactory training in smell recovery. Methods An extensive search was performed through different databases in order to find articles analyzing the efficacy of olfactory training as a treatment for olfactory dysfunction. Methodological quality of primary studies within the final sample was assessed following PRISMA guidelines. Standardized mean differences in pre–post olfactory training groups, and also in experimental-control and pre-follow up if possible, were computed by Hedges’ g effect size statistic. Each effect size was weighted by its inverse variance. Results Final sample was composed of 36 articles (45 pre–post effect sizes). Contrasts were performed separately for odor identification, odor discrimination, odor threshold and general olfactory function. Moderate to large and heterogeneous effect was obtained for olfactory function (g = 0.755, k = 45, SE = 0.093, CI 95% = [0.572, 0.937]), different moderators had a significant effects, such as, training duration, age and anosmia diagnosis. Conclusion Olfactory training was found to have a positive and significant effect on rehabilitating the olfactory function.

Objectives In this study, we horizontally compared olfactory function and interleukin-6 levels in bipolar disorder (BD) patients with manic and depressive episodes with those in healthy controls. We also compared these variables longitudinally between patients in the acute versus euthymic phase, and assessed the correlation between olfactory function and interleukin-6 in BD patients overall. The purpose of this study was to search potential biomarkers for early diagnosis and efficacy evaluation of BD, and to provide more clinical evidence for exploring the hypothesis of neuroimmune pathways in BD. Methods The study included 50 manic BD patients, 31 depressive BD patients, and 59 healthy controls, and all patients were followed until they entered the euthymic phase. Olfactory sensitivity (OS) and olfactory identification (OI) were evaluated via the Sniffin’ Sticks test. We collected blood samples and measured serum interleukin-6 levels. Results The results showed that the OS and OI in manic BD group and depressive BD group were significantly lower than those in healthy controls ( P  < 0.05, Cohen’s d = 0.657, 0.446, η 2  = 0.744, 0.676, respectively), and the OI in euthymic manic BD group and euthymic depressive BD group were significantly lower than those in healthy controls ( P  < 0.0167, η 2  = 0.72, 0.653, respectively). OS returned to normal levels with remission of the disease ( P  < 0.0167, η 2  = 12.106), while OI was continuously impaired. Serum interleukin-6 decreased with remission in manic BD ( P  = 0.038, η 2  = 12.118), but did not return to normal levels ( P  = 0.006, η 2  = 0.719). OS was negatively correlated with serum interleukin-6 in manic BD patients ( r = -0.386, P  = 0.006). Conclusion The dynamic recovery of OS (impaired in acute phase, restored in euthymia) suggests its potential as a disease-activity biomarker in BD, while persistent OI deficits may reflect trait-related neurobiological features. However, their specificity and clinical utility require rigorous validation. There is a potential correlation between inflammatory activity and olfactory dysfunction in manic BD patients, but its causal relationship and specific mechanism need to be further verified.

Olfactory training (OT), smelling odours, twice per day for an extended period, can improve the olfactory function in adults. The aim of the current study was to investigate whether OT can improve the olfactory function of children aged 8 years old. Odour thresholds and odour identification ability were compared between two groups across three separate testing sessions (baseline, 6-week post-baseline, 12-week post-baseline). After the baseline test, the control group (n = 21) completed 6 weeks of bi-daily OT with odourless stimuli, whereas the experiment group (n = 20) completed 6 weeks of bi-daily OT, smelling four different odours (eucalyptus, lemon, clove, rose). A repeated measure analysis of variance was used to test for group differences across the three testing sessions. Six weeks after OT had been completed, participants in the experiment group demonstrated a significant increase in odour identification scores (9.95 to 11.20), compared to the control group who demonstrated no increase (10.48 to 10.48). No group differences in odour threshold ability were found.Conclusion: Six weeks of OT enhances odour identification ability, but not odour thresholds, in 8-year-old children.What is Known:• Smell loss and dysfunction are associated with negative health outcomes such as depression and increased risk of consuming contaminated food.• Olfactory training can improve sense of smell in adults.What is New:• Olfactory training improves odour identification ability in 8-year-olds.• Olfactory training does not appear to enhance odour acuity in 8-year-olds.

Olfactory dysfunction is often accompanied with anxiety- and depressive-like behaviors in depressive patients. Impaired neurogenesis in hippocampus and subventricular zone (SVZ)-olfactory bulb (OB) contribute to anxiety- and depressive-like behaviors and olfactory dysfunctions. However, the underlying mechanisms of olfactory dysfunction remain unclear. Our previous study indicates that adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2), could affect the activity and sensitivity of glucocorticoid receptor (GR) and mediate impaired hippocampal neurogenesis, which contribute the development of depression. In the present study, we further identified the roles of APPL2 in olfactory functions. APPL2 Tg mice displayed higher GR activity and less capacity of neurogenesis at olfactory system with less olfactory sensitivity than WT mice, indicating that APPL2 could be a potential therapeutic target for depression and olfactory deficits. We then studied the effects of baicalin, a medicinal herbal compound, on modulating APPL2/GR signaling pathway for promoting neurogenesis and antidepressant as well as improving olfactory functions. Baicalin treatment inhibited APPL2/GR signaling pathway and improved neurogenesis at SVZ, OB, and hippocampus in APPL2 Tg mice and chronic corticosterone-induced depression mouse model. Behavioral tests revealed that baicalin attenuated depressive- and anxiety-like behaviors and improve olfactory functions in the chronic depression mouse model and APPL2 Tg mice. Taken together, APPL2 could be a novel therapeutic target for improving depressant-related olfactory dysfunctions and baicalin could inhibit APPL2-mediated GR hyperactivity and promote adult neurogenesis, subsequently releasing depressive and anxiety symptoms and improving olfactory functions for antidepressant therapy.

Abstract Study Objectives To evaluate the prevalence and clinical characteristics of isolated REM sleep behavior disorder (iRBD) among a general population of elderly Japanese people. Methods This epidemiological study targeted 2714 elderly residents (76.0 ± 8.0 years, 52.9% female) of a rural community. Questionnaires including the REM sleep behavior disorder single question and demographic information were distributed. All respondents with the question positive were interviewed by telephone. Respondents suspected of having iRBD proceeded to face-to-face interviews and underwent video-polysomnography and neurological/neuropsychological examination. These results were compared to those of previously diagnosed clinical iRBD patients in our sleep clinic. Results Of 1464 respondents to the questionnaire, 18 respondents were diagnosed as iRBD (1.23 [0.66–1.79]%), including eight respondents who satisfied diagnostic criteria with REM sleep without atonia (RWA) above the cut-off value (0.54 [0.17–0.92]%) and 10 respondents who had clear dream enactment behaviors but not RWA above the cut-off (provisionally diagnosed iRBD; p-iRBD) (0.69 [0.26–1.11]%). Severity of RBD and RWA of the population-based iRBD were compatible with those of the clinical iRBD. Half of the population-based iRBD showed orthostatic hypotension and they showed lower olfactory function than population-based p-iRBD and non-RBD. However, their olfactory and cognitive functions were higher than those in the clinical iRBD patients. Conclusions Prevalence of iRBD in Japanese elderly people was comparable with the rate reported from other countries. Population-based iRBD/p-iRBD showed lower neurodegenerative loading than clinical iRBD in spite of comparable disease duration of RBD, that may indicate their lower risk of future neurodegeneration.

Background Prednisolone has been suggested as a treatment for olfactory disorders after COVID-19, but evidence is scarce. Hence, we aimed to determine the efficacy of a short oral prednisolone treatment on patients with persistent olfactory disorders after COVID-19. Methods We performed a randomized, double-blind, placebo-controlled, single-centered trial in the Netherlands. Patients were included if they were > 18 years old and if they had persistent (> 4 weeks) olfactory disorders within 12 weeks after a confirmed COVID-19 test. The treatment group received oral prednisolone 40 mg once daily for 10 days and the placebo group received matching placebo. In addition, all patients performed olfactory training. The primary outcome was the objective olfactory function on Sniffin’ Sticks Test (SST) 12 weeks after the start of treatment, measured in Threshold-Discrimination-Identification (TDI) score. Secondary outcomes were objective gustatory function assessed by the Taste Strip Test (TST) and subjective self-reported outcomes on questionnaires about olfactory, gustatory and trigeminal function, quality of life, and nasal symptoms. The CONSORT 2010 guideline was performed . Results Between November 2021 and February 2022, we included 115 eligible patients, randomly assigned to the treatment ( n  = 58) or placebo group ( n  = 57). No difference in olfactory function between groups was obtained after 12 weeks. Median TDI score on SST was 26.8 (IQR 23.6-29.3) in the placebo group and 28.8 (IQR 24.0-30.9) in the prednisolone group, with a median difference of - 1.5 (-3.0 to 0.25). There was similar improvement on olfactory function in both groups after 12 weeks. Furthermore, on secondary outcomes, we obtained no differences between groups. Conclusions This trial shows that prednisolone does not improve olfactory function after COVID-19. Therefore, we recommend not prescribing prednisolone for patients with persistent olfactory disorders after COVID-19. Trial registration This trial is registered on the ISRCTN registry with trial ID ISRCTN70794078.

Few population-based studies including younger adults have examined the potential of olfactory function tests to capture the degree of atrophy in memory-associated brain regions, which cannot be adequately explained by cognitive function tests screening for cognitive impairment. This population-based study investigated associations between high-resolution olfactory test data with few odours and grey matter volumes (GMVs) of the left and right hippocampi, amygdala, parahippocampi, and olfactory cortex, while accounting for differences in cognitive decline, in 1444 participants (aged 31–91 years). Regression analyses included intracranial volume (ICV)-normalised GMVs of eight memory-related regions as objective variables and age, sex, education duration, smoking history, olfaction test score, and the Montreal Cognitive Assessment-Japanese version (MoCA-J) score as explanatory variables. Significant relationships were found between olfactory test scores and ICV-normalised GMVs of the left and right hippocampi and left amygdala ( p  = 0.020, 0.024, and 0.028, respectively), adjusting for the MoCA-J score. The olfactory test score was significantly related to the right amygdalar GMV ( p  = 0.020) in older adults (age ≥ 65 years). These associations remained significant after applying Benjamini–Hochberg multiple testing correction (false discovery rate < 0.1). Therefore, olfactory and cognitive function tests may efficiently capture the degree of atrophy in the hippocampi and amygdala, especially in older adults.

Purpose Loss of smell decreases the quality of life and contributes to the failure in recognizing hazardous substances. Given the relevance of olfaction in daily life, it is important to recognize an undiagnosed olfactory dysfunction to prevent these possible complications. Up to now, the prevalence of smell disorders in Italy is unknown due to a lack of epidemiological studies. Hence, the primary aim of this study was to evaluate the prevalence of olfactory dysfunction in a sample of Italian adults. Methods Six hundred and thirty-three participants (347 woman and 286 men; mean age 44.9 years, SD 17.3, age range 18–86) were recruited from 10 distinct Italian regions. Participants were recruited using a convenience sapling and were divided into six different age groups: 18–29 years ( N  = 157), 30–39 years ( N  = 129), 40–49 years ( N  = 99), 50–59 years ( N  = 106), > 60 years ( N  = 142). Olfactory function, cognitive abilities, cognitive reserve, and depression were assessed, respectively, with: Sniffin’ Sticks 16-item Odor Identification Test, Montreal Cognitive Assessment, Cognitive Reserve Index, and the Beck Depression Inventory. Additionally, socio-demographic data, medical history, and health-related lifestyle information were collected. Results About 27% of participants showed an odor identification score < 12 indicating hyposmia. Multiple regression analysis revealed that OI was significantly correlated with age, sex, and cognitive reserve index, and young women with high cognitive reserve index showing the highest olfactory scores. Conclusion This study provides data on the prevalence of olfactory dysfunction in different Italian regions.