Evaluation of the Neuroanatomical Basis of Olfactory Dysfunction in the General Population

Lu, Ran; Aziz, N. Ahmad; Reuter, Martin; Stöcker, Tony; Breteler, Monique M.B.

doi:10.1001/jamaoto.2021.2026

Cited by 14 publications

(16 citation statements)

References 41 publications

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“…Indeed, we observed a decrease in OBV and VGLUT2 staining as a function of age. OBV correlates with olfactory performance independent of confounding factors such as gender, nasal congestion, and smoking status (Lu et al, 2021 (Maresh et al, 2008;Mobley et al, 2014;Richard et al, 2010). The divergence of our results from published data (Maresh et al, 2008) may reflect: differences in 1) the sample size; seven samples as compared to 39 from 23 subjects in our study, 2) the analytic approach; two subgroups (over 50 and under 50 years) and performed an unpaired t test, whereas we chose the linear regression model to look for a correlation between age and amount of glomeruli, and 3) the measurement approach; manual count of individual glomeruli, while we found it difficult to identify and count distinct glomeruli and instead used the overall VGLUT2 staining to better identify glomerular synapses.…”

Section: Discussionmentioning

confidence: 96%

“…Indeed, we observed a decrease in OBV and VGLUT2 staining as a function of age. OBV correlates with olfactory performance independent of confounding factors such as gender, nasal congestion, and smoking status (Lu et al., 2021). Accordingly, decreasing OBV with age may represent a histopathological correlate for age‐related smell loss.…”

Section: Discussionmentioning

confidence: 99%

“…Even though human as well as rodent OE is capable of lifelong regeneration, thanks to the persistence of stem and progenitor cells within the basal cell population (Brann et al., 2015; Durante et al., 2020; Schwob, 2002), a decline in smell function with age is well known in humans (Doty et al., 1984; Lu et al., 2021; Vennemann et al., 2008; Zhang & Wang, 2017). Deterioration in olfaction among the elderly likely depends to some degree on the extent of pathological alterations in the area, structure, and composition of the OE.…”

Section: Introductionmentioning

confidence: 99%

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Integrated age‐related immunohistological changes occur in human olfactory epithelium and olfactory bulb

Fitzek

Patel

Solomon

et al. 2022

J of Comparative Neurology

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Olfactory epithelium (OE) is capable of lifelong regeneration due to presence of basal progenitor cells that respond to injury or neuronal loss with increased activity. However, this capability diminishes with advancing age and a decrease in odor perception in older individuals is well established. To characterize changes associated with age in the peripheral olfactory system, an in-depth analysis of the OE and its neuronal projections onto the olfactory bulb (OB) as a function of age was performed. Human olfactory tissue autopsy samples from 36 subjects with an average age of 74.1 years were analyzed.Established cell type-specific antibodies were used to identify OE component cells in whole mucosal sheets and epithelial sections as well as glomeruli and periglomerular structures in OB sections. With age, a reduction in OE area occurs across the mucosa progressing in a posterior-dorsal direction. Deterioration of the olfactory system is accompanied with diminution of neuron-containing OE, mature olfactory sensory neurons (OSNs) and OB innervation. On an individual level, the neuronal density within the epithelium appears to predict synapse density within the OB. The innervation of the OB is uneven with higher density at the ventral half that decreases with age as opposed to stable innervation at the dorsal half. Respiratory metaplasia, submucosal cysts, and neuromata, were commonly identified in aged OE. The finding of respiratory metaplasia and aneuronal epithelium with reduction in global basal cells suggests a progression of stem cell quiescence as an underlying pathophysiology of age-related smell loss in humans.

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Section: Discussionmentioning

confidence: 96%

“…Indeed, we observed a decrease in OBV and VGLUT2 staining as a function of age. OBV correlates with olfactory performance independent of confounding factors such as gender, nasal congestion, and smoking status (Lu et al., 2021). Accordingly, decreasing OBV with age may represent a histopathological correlate for age‐related smell loss.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Integrated age‐related immunohistological changes occur in human olfactory epithelium and olfactory bulb

Fitzek

Patel

Solomon

et al. 2022

J of Comparative Neurology

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“…While the association between olfactory function and olfactory bulb (OB) volume has been well described in previous studies [15], information on different bulb configurations is sparse [16]. In a recent study, Lu et al [17] report an association between olfactory function and volumes of central olfactory structures in older age groups, primarily mediated through OB volume. Even though these morphological differences have recently been proposed to provide diagnostic information on different aetiologies of olfactory dysfunction [18], no overview of bulb variations or classification system currently exists.…”

Section: Introductionmentioning

confidence: 99%

Cortical Atrophy, White Matter Lesions, and Bulb Configuration in Patients with Idiopathic Olfactory Loss and Other Causes of Olfactory Loss

Fjældstad

Ovesen

Dalby

2021

ORL

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Introduction: While magnetic resonance imaging (MRI) is not included in the current guidelines for diagnosing olfactory disorders in the most recent position paper on olfactory dysfunction, both 1.5T and 3T MRI are commonly used in the diagnostic workup of many patients with olfactory loss. Often, MRI is used to rule out intracranial tumours, but other useful information may be obtained from MRI scans in these patients. The potential of MRI in olfactory loss depends on sufficient knowledge of structural changes in different aetiologies of olfactory loss. We present common clinical MRI findings in olfactory loss and evaluate the usefulness of structural integrity scores in differentiating between aetiologies. Methods: In this study, we investigated if white matter hyperintensities (WMHs, measured by Fazekas score), global cortical atrophy (GCA), and medial temporal lobe atrophy (MTA) are more common in patients with idiopathic olfactory loss than in patients with acquired olfactory loss due to other aetiologies. Furthermore, we compared olfactory bulb (OB) configurations in different olfactory loss aetiologies. Results: In 88 patients with olfactory loss, WMHs, GCA, and MTA were not more significant findings on MRI in idiopathic olfactory loss (n = 51) compared with other causes of acquired olfactory loss (Fazekas score p = 0.2977; GCA score p = 0.6748; MTA score p = 0.7851). Bulb configurations differed in patients suffering from post-traumatic olfactory loss and may aid in identifying the underlying aetiology in patients where trauma is among the suspected causes of olfactory loss. Conclusion: We recommend that structural MRI with an OB sequence is included in the diagnostic evaluation of olfactory loss with suspected congenital and post-traumatic aetiology and should be considered in idiopathic olfactory loss with suspected central aetiology (e.g., tumour).

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“…age and was worse in men than in women. 2 Olfactory function was inversely associated with self-reported nasal patency. A strong magnitude of association was found between olfactory bulb volume (OBV) and odor identification test performance.…”

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confidence: 98%

Olfactory Bulb Volume—A Novel Preclinical Biomarker for Smell Loss and Neurodegenerative Disease

Das

2021

JAMA Otolaryngol Head Neck Surg

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Neurodegenerative disorders, such as Alzheimer dementia and Parkinson disease, are disabling diseases that present a burden on society that rivals the costs of cancer and heart disease. Although current therapies are often unsuccessful at reversing the progression of these diseases, early detection in patients who are at risk of neurodegenerative disease could allow for timely interventions to delay and minimize the loss of brain function over time.Olfactory impairment has been shown to be a preclinical marker for Alzheimer dementia, which may predate the onset of dementia by many years. 1 However, the screening for olfactory impairment is extremely limited in current clinical practice, and the need exists for better biomarkers that can identify at-risk patients and demonstrate real-time response to therapies. Clinical biomarkers from studies that were performed in the workup of patients with neurodegenerative diseases, such as magnetic resonance imaging (MRI) scans, are ideal for identifying sensitive and specific changes that occur in advance of symptomatic disease.In this issue of JAMA Otolaryngology-Head & Neck Surgery, Lu et al 2 report their analysis of initial data from the Rhineland Study to glean insights into the neuroanatomical correlates of smell loss. The Rhineland Study is an ongoing prospective cohort study funded by the German Center for Neurodegenerative Diseases that began in 2016. 3 By its completion, the study will have included up to 30 000 participants from Bonn, Germany, and assessed their physical and mental health over their lifespan. The main aims of the study are to investigate the modifiable and nonmodifiable causes of neurodegenerative diseases and to find biomarkers that identify individuals who are at risk for such diseases. Participants in the study undergo extensive data collection (by responding to questionnaires), clinical sample testing, and highresolution 3-T MRI scans. 3 In their cross-sectional study, Lu et al 2 investigated whether a neuroanatomical correlate for olfactory dysfunction could be found. They examined the volumes in several regions of the brain that have a role in processing olfactory information, including the olfactory bulbs, entorhinal cortex, amygdala, parahippocampal cortex, hippocampus, insular cortex, and lateral and medial orbitofrontal cortex and correlated these measurements with odor identification function. These data were collected from 541 participants in the Rhineland Study, which is an impressive number of participants to have prospectively collected high-resolution MRI findings and odor identification test scores. The authors' analyses confirmed that olfactory function decreased with increasing

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Evaluation of the Neuroanatomical Basis of Olfactory Dysfunction in the General Population

Cited by 14 publications

References 41 publications

Integrated age‐related immunohistological changes occur in human olfactory epithelium and olfactory bulb

Integrated age‐related immunohistological changes occur in human olfactory epithelium and olfactory bulb

Cortical Atrophy, White Matter Lesions, and Bulb Configuration in Patients with Idiopathic Olfactory Loss and Other Causes of Olfactory Loss

Olfactory Bulb Volume—A Novel Preclinical Biomarker for Smell Loss and Neurodegenerative Disease

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