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Neuropsychology Review Mar 2024Olfactory training (OT), or smell training,consists of repeated exposure to odorants over time with the intended neuroplastic effect of improving or remediating... (Review)
Review
Olfactory training (OT), or smell training,consists of repeated exposure to odorants over time with the intended neuroplastic effect of improving or remediating olfactory functioning. Declines in olfaction parallel declines in cognition in various pathological conditions and aging. Research suggests a dynamic neural connection exists between olfaction and cognition. Thus, if OT can improve olfaction, could OT also improve cognition and support brain function? To answer this question, we conducted a systematic review of the literature to determine whether there is evidence that OT translates to improved cognition or altered brain morphology and connectivity that supports cognition. Across three databases (MEDLINE, Scopus, & Embase), 18 articles were identified in this systematic review. Overall, the reviewed studies provided emerging evidence that OT is associated with improved global cognition, and in particular, verbal fluency and verbal learning/memory. OT is also associated with increases in the volume/size of olfactory-related brain regions, including the olfactory bulb and hippocampus, and altered functional connectivity. Interestingly, these positive effects were not limited to patients with smell loss (i.e., hyposmia & anosmia) but normosmic (i.e., normal ability to smell) participants benefitted as well. Implications for practice and research are provided.
Topics: Humans; Brain; Cognition; Olfaction Disorders; Olfactory Training; Smell
PubMed: 36725781
DOI: 10.1007/s11065-022-09573-0 -
Brazilian Journal of Otorhinolaryngology 2022SARS-CoV-2 is the pathogen of COVID-19. The virus is composed of the spike, membrane and envelope. On physiological smell, odoriferous substances bind to proteins... (Review)
Review
INTRODUCTION
SARS-CoV-2 is the pathogen of COVID-19. The virus is composed of the spike, membrane and envelope. On physiological smell, odoriferous substances bind to proteins secreted by sustentacular cells in order to be processed by olfactory receptor neurons. Olfactory disorder is one of the main manifestations of COVID-19, however, research is still required to clarify the mechanism involved in SARS-CoV-2 induced anosmia.
OBJECTIVE
This article aims to analyze current scientific evidence intended to elucidate the pathophysiological relationship between COVID-19 and the cause of olfactory disorders.
METHODS
Pubmed, Embase, Scopus and ScienceDirect were used to compose this article. The research was conducted on November 24th, 2020. Original articles with experimental studies in human, animal and in vitro, short communications, viewpoint, published in the English language and between 2019 and 2020 were included, all related to the pathophysiological relationship between olfactory disorders and COVID-19 infection.
RESULTS
Both human cell receptors ACE2 and TMPRSS2 are essential for the SARS-CoV-2 entrance. These receptors are mostly present in the olfactory epithelium cells, therefore, the main hypothesis is that anosmia is caused due to damage to non-neuronal cells which, thereafter, affects the normal olfactory metabolism. Furthermore, magnetic resonance imaging studies exhibit a relationship between a reduction on the neuronal epithelium and the olfactory bulb atrophy. Damage to non-neuronal cells explains the average recovery lasting a few weeks. This injury can be exacerbated by an aggressive immune response, which leads to damage to neuronal cells and stem cells inducing a persistent anosmia. Conductive anosmia is not sufficient to explain most cases of COVID-19 induced anosmia.
CONCLUSION
Olfactory disorders such as anosmia and hyposmia can be caused by COVID-19, the main mechanism is associated with olfactory epithelium damage, targeting predominantly non-neuronal cells. However, neuronal cells can also be affected, worsening the condition of olfactory loss.
Topics: Angiotensin-Converting Enzyme 2; Animals; Anosmia; COVID-19; Humans; Olfaction Disorders; SARS-CoV-2; Smell
PubMed: 33965353
DOI: 10.1016/j.bjorl.2021.04.001 -
Neuroscience and Biobehavioral Reviews Jun 2021Olfactory impairment is a common clinical motif across neurodevelopmental disorders, suggesting olfactory circuits are particularly vulnerable to disease processes and... (Review)
Review
Olfactory impairment is a common clinical motif across neurodevelopmental disorders, suggesting olfactory circuits are particularly vulnerable to disease processes and can provide insight into underlying disease mechanisms. The mouse olfactory bulb is an ideal model system to study mechanisms of neurodevelopmental disease due to its anatomical accessibility, behavioral relevance, ease of measuring circuit input and output, and the feature of adult neurogenesis. Despite the clinical relevance and experimental benefits, olfactory testing across animal models of neurodevelopmental disease has been inconsistent and non-standardized. Here we performed a systematic literature review of olfactory function testing in mouse models of neurodevelopmental disorders, and identified intriguing inconsistencies that include evidence for both increased and decreased acuity in odor detection in various mouse models of Autism Spectrum Disorder (ASD). Based on our identified gaps in the literature, we recommend direct comparison of different mouse models of ASD using standardized tests for odor detection and discrimination. This review provides a framework to guide future olfactory function testing in mouse models of neurodevelopmental diseases.
Topics: Adult; Animals; Autism Spectrum Disorder; Humans; Mice; Neurogenesis; Olfaction Disorders; Olfactory Bulb; Smell
PubMed: 33610612
DOI: 10.1016/j.neubiorev.2021.02.024 -
Neuroradiology Jan 2023The neurotropism of SARS-CoV-2 and the consequential damage to the olfactory system have been proposed as one of the possible underlying causes of olfactory dysfunction... (Meta-Analysis)
Meta-Analysis
PURPOSE
The neurotropism of SARS-CoV-2 and the consequential damage to the olfactory system have been proposed as one of the possible underlying causes of olfactory dysfunction in COVID-19. We aimed to aggregate the results of the studies which reported imaging of the olfactory system of patients with COVID-19 versus controls.
METHODS
PubMed and EMBASE were searched to identify relevant literature reporting the structural imaging characteristics of the olfactory bulb (OB), olfactory cleft, olfactory sulcus (OS), or olfactory tract in COVID-19 patients. Hedge's g and weighted mean difference were used as a measure of effect size. Quality assessment, subgroup analyses, meta-regression, and sensitivity analysis were also conducted.
RESULTS
Ten studies were included in the qualitative synthesis, out of which seven studies with 183 cases with COVID-19 and 308 controls without COVID-19 were enrolled in the quantitative synthesis. No significant differences were detected in analyses of right OB volume and left OB volume. Likewise, right OS depth and left OS depth were also not significantly different in COVID-19 cases compared to non-COVID-19 controls. Also, we performed subgroup analysis, meta-regression, and sensitivity analysis to investigate the potential effect of confounding moderators.
CONCLUSION
The findings of this review did not confirm alterations in structural imaging of the olfactory system, including OB volume and OS depth by Covid-19 which is consistent with the results of recent histopathological evaluations.
Topics: Humans; Olfaction Disorders; COVID-19; SARS-CoV-2; Magnetic Resonance Imaging; Olfactory Bulb
PubMed: 35843987
DOI: 10.1007/s00234-022-03014-8 -
The Laryngoscope Jun 2022Olfactory dysfunction (OD) is a common presenting symptom of COVID-19 infection. Radiological imaging of the olfactory structures in patients with COVID-19 and OD can... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Olfactory dysfunction (OD) is a common presenting symptom of COVID-19 infection. Radiological imaging of the olfactory structures in patients with COVID-19 and OD can potentially shed light on its pathogenesis, and guide clinicians in prognostication and intervention.
METHODS
PubMed, Embase, Cochrane, SCOPUS were searched from inception to August 1, 2021. Three reviewers selected observational studies, case series, and case reports reporting radiological changes in the olfactory structures, detected on magnetic resonance imaging, computed tomography, or other imaging modalities, in patients aged ≥18 years with COVID-19 infection and OD, following preferred reporting items for systematic reviews and meta-analyses guidelines and a PROSPERO-registered protocol (CRD42021275211). We described the proportion of radiological outcomes, and used random-effects meta-analyses to pool the prevalence of olfactory cleft opacification, olfactory bulb signal abnormalities, and olfactory mucosa abnormalities in patients with and without COVID-19-associated OD.
RESULTS
We included 7 case-control studies (N = 353), 11 case series (N = 154), and 12 case reports (N = 12). The pooled prevalence of olfactory cleft opacification in patients with COVID-19 infection and OD (63%, 95% CI = 0.38-0.82) was significantly higher than that in controls (4%, 95% CI = 0.01-0.13). Conversely, similar proportions of cases and controls demonstrated olfactory bulb signal abnormalities (88% and 94%) and olfactory mucosa abnormalities (2% and 0%). Descriptive analysis found that 55.6% and 43.5% of patients with COVID-19 infection and OD had morphological abnormalities of the olfactory bulb and olfactory nerve, respectively, while 60.0% had abnormal olfactory bulb volumes.
CONCLUSION
Our findings implicate a conductive mechanism of OD, localized to the olfactory cleft, in approximately half of the affected COVID-19 patients. Laryngoscope, 132:1260-1274, 2022.
Topics: Adolescent; Adult; COVID-19; Humans; Olfaction Disorders; Olfactory Bulb; Olfactory Mucosa; Smell
PubMed: 35318656
DOI: 10.1002/lary.30078 -
Journal of Neurology Nov 2023Coronavirus disease 2019 (COVID-19) has been associated with nervous system involvement, with more than one-third of COVID-19 patients experiencing neurological... (Review)
Review
BACKGROUND
Coronavirus disease 2019 (COVID-19) has been associated with nervous system involvement, with more than one-third of COVID-19 patients experiencing neurological manifestations. Utilizing a systematic review, this study aims to summarize brain MRI findings in COVID-19 patients presenting with neurological symptoms.
METHODS
Systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) checklist. The electronic databases of PubMed/MEDLINE, Embase, Scopus, and Web of Science were systematically searched for literature addressing brain MRI findings in COVID-19 patients with neurological symptoms.
RESULTS
25 publications containing a total number of 3118 COVID-19 patients with neurological symptoms who underwent MRI were included. The most common MRI findings and the respective pooled incidences in decreasing order were acute/subacute infarct (22%), olfactory bulb abnormalities (22%), white matter abnormalities (20%), cerebral microbleeds (17%), grey matter abnormalities (12%), leptomeningeal enhancement (10%), ADEM (Acute Disseminated Encephalomyelitis) or ADEM-like lesions (10%), non-traumatic ICH (10%), cranial neuropathy (8%), cortical gray matter signal changes compatible with encephalitis (8%), basal ganglia abnormalities (5%), PRES (Posterior Reversible Encephalopathy Syndrome) (3%), hypoxic-ischemic lesions (4%), venous thrombosis (2%), and cytotoxic lesions of the corpus callosum (2%).
CONCLUSION
The present study revealed that a considerable proportion of patients with COVID-19 might harbor neurological abnormalities detectable by MRI. Among various findings, the most common MRI alterations are acute/subacute infarction, olfactory bulb abnormalities, white matter abnormalities, and cerebral microbleeds.
PubMed: 37535100
DOI: 10.1007/s00415-023-11914-9 -
Brain Sciences Jul 2021Olfactory decline is an early symptom of Alzheimer's disease (AD) and is a predictor of conversion from mild cognitive impairment (MCI) to AD. Olfactory decline could... (Review)
Review
Olfactory decline is an early symptom of Alzheimer's disease (AD) and is a predictor of conversion from mild cognitive impairment (MCI) to AD. Olfactory decline could reflect AD-related atrophy of structures related to the sense of smell. The aim of this study was to verify whether the presence of a clinical diagnosis of AD or MCI is associated with a volumetric decrease in the olfactory bulbs (OB) and the primary olfactory cortex (POC). We conducted two systematic reviews, one for each region and a meta-analysis. We collected articles from PsychNet, PubMed, Ebsco, and ProQuest databases. Results showed large and heterogeneous effects indicating smaller OB volumes in patients with AD (k = 6, = -1.21, 95% CI [-2.19, -0.44]) and in patients with MCI compared to controls. There is also a trend for smaller POC in patients with AD or MCI compared to controls. Neuroanatomical structures involved in olfactory processing are smaller in AD and these volumetric reductions could be measured as early as the MCI stage.
PubMed: 34439629
DOI: 10.3390/brainsci11081010 -
Chinese Medical Sciences Journal =... Mar 2022Background Anosmia is one of the symptoms in individuals with SARS-CoV-2 infection. In anosmic patients, SARS-CoV-2 temporarily alters the signaling process in olfactory...
Background Anosmia is one of the symptoms in individuals with SARS-CoV-2 infection. In anosmic patients, SARS-CoV-2 temporarily alters the signaling process in olfactory nerve cells and olfactory bulb (OB), which eventually damages the structure of the olfactory epithelium, leading to a permanent disorder in the olfactory pathway that this damaged structure is showed in MRI imaging Methods Two investigators independently searched four databases consisting of PubMed, ProQuest, Scopus, and Web of Science for relevant records as of November 11, 2020 with no time, space, and language restrictions. Google Scholar was also searched for the related resources within the time limit of 2020. All the found articles were reviewed based on the PRISMA flow diagram. Qualitative studies, case reports, editorials, letters, and other non-original studies were excluded from this systematic analysis. Results Initial search yielded 434 records. After reviewing the titles and abstracts, we selected 74 articles; finally, 8 articles were depicted to be investigated and read in full text. The obtained results showed an increase in the width and volume of the olfactory cleft (OC), complete or partial destruction of OC, and complete occlusion of OC in COVID-19 patients. Deformation and degeneration as well as a subtle asymmetry were evident in the OBs. Computed tomography (CT), meganetic resonance imaging (MRI), and positron emission tomography (PET) were used to detect the outcomes of anosmia in these studies. Conclusions The changes in OC are greater than those in OB in patients with COVID-19, mainly due to the inflammatory and immune responses in OC. However, fewer changes in OB are due to neurological or vascular disorders. Topical steroid therapy and topical saline can be helpful.
PubMed: 35256044
DOI: 10.24920/003982 -
Brain Structure & Function Jan 2022Brain structural features of healthy individuals are associated with olfactory functions. However, due to the pathophysiological differences, congenital and acquired...
Brain structural features of healthy individuals are associated with olfactory functions. However, due to the pathophysiological differences, congenital and acquired anosmia may exhibit different structural characteristics. A systematic review was undertaken to compare brain structural features between patients with congenital and acquired anosmia. A systematic search was conducted using PubMed/MEDLINE and Scopus electronic databases to identify eligible reports on anosmia and structural changes and reported according to PRISMA guidelines. Reports were extracted for information on demographics, psychophysical evaluation, and structural changes. Then, the report was systematically reviewed based on various aetiologies of anosmia in relation to (1) olfactory bulb, (2) olfactory sulcus, (3) grey matter (GM), and white matter (WM) changes. Twenty-eight published studies were identified. All studies reported consistent findings with strong associations between olfactory bulb volume and olfactory function across etiologies. However, the association of olfactory function with olfactory sulcus depth was inconsistent. The present study observed morphological variations in GM and WM volume in congenital and acquired anosmia. In acquired anosmia, reduced olfactory function is associated with reduced volumes and thickness involving the gyrus rectus, medial orbitofrontal cortex, anterior cingulate cortex, and cerebellum. These findings contrast to those observed in congenital anosmia, where a reduced olfactory function is associated with a larger volume and higher thickness in parts of the olfactory network, including the piriform cortex, orbitofrontal cortex, and insula. The present review proposes that the structural characteristics in congenital and acquired anosmia are altered differently. The mechanisms behind these changes are likely to be multifactorial and involve the interaction with the environment.
Topics: Anosmia; Brain; Gray Matter; Humans; Magnetic Resonance Imaging; Olfaction Disorders
PubMed: 34635958
DOI: 10.1007/s00429-021-02397-3 -
Molecular Neurobiology Oct 2022Neural regeneration has troubled investigators worldwide in the past decades. Currently, cell transplantation emerged as a breakthrough targeted therapy for spinal cord... (Review)
Review
Neural regeneration has troubled investigators worldwide in the past decades. Currently, cell transplantation emerged as a breakthrough targeted therapy for spinal cord injury (SCI) in the neurotrauma field, which provides a promising strategy in neural regeneration. Olfactory ensheathing cells (OECs), a specialized type of glial cells, is considered as the excellent candidate due to its unique variable and intrinsic regeneration-supportive properties. In fact, OECs could support olfactory receptor neuron turnover and axonal extension, which is essential to maintain the function of olfactory nervous system. Hitherto, an increasing number of literatures demonstrate that transplantation of OECs exerts vital roles in neural regeneration and functional recovery after neural injury, including central and peripheral nervous system. It is common knowledge that the deteriorating microenvironment (ischemia, hypoxia, scar, acute and chronic inflammation, etc.) resulting from injured nervous system is adverse for neural regeneration. Interestingly, recent studies indicated that OECs could promote neural repair through improvement of the disastrous microenvironments, especially to the overwhelmed inflammatory responses. Although OECs possess unusual advantages over other cells for neural repair, particularly in SCI, the mechanisms of OEC-mediated neural repair are still controversial with regard to anti-inflammation. Therefore, it is significant to summarize the anti-inflammation property of OECs, which is helpful to understand the biological characteristics of OECs and drive future studies. Here, we mainly focus on the anti-inflammatory role of OECs to make systematic review and discuss OEC-based therapy for CNS injury.
Topics: Anti-Inflammatory Agents; Cell Transplantation; Humans; Nerve Regeneration; Neuroglia; Olfactory Bulb; Spinal Cord; Spinal Cord Injuries
PubMed: 35962300
DOI: 10.1007/s12035-022-02983-4