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      Age-Related Olfactory Dysfunction: Epidemiology, Pathophysiology, and Clinical Management

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          Abstract

          Like other sensory systems, olfactory function deteriorates with age. Epidemiological studies have revealed that the incidence of olfactory dysfunction increases at the age of 60 and older and males are more affected than females. Moreover, smoking, heavy alcohol use, sinonasal diseases, and Down’s syndrome are associated with an increased incidence of olfactory dysfunction. Although the pathophysiology of olfactory dysfunction in humans remains largely unknown, studies in laboratory animals have demonstrated that both the peripheral and central olfactory nervous systems are affected by aging. Aged olfactory neuroepithelium in the nasal cavity shows the loss of mature olfactory neurons, replacement of olfactory neuroepithelium by respiratory epithelium, and a decrease in basal cell proliferation both in the normal state and after injury. In the central olfactory pathway, a decrease in the turnover of interneurons in the olfactory bulb (OB) and reduced activity in the olfactory cortex under olfactory stimulation is observed. Recently, the association between olfactory impairment and neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), has gained attention. Evidence-based pharmacotherapy to suppress or improve age-related olfactory dysfunction has not yet been established, but preliminary results suggest that olfactory training using odorants may be useful to improve some aspects of age-related olfactory impairment.

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          Stages in the development of Parkinson's disease-related pathology.

          The synucleinopathy, idiopathic Parkinson's disease, is a multisystem disorder that involves only a few predisposed nerve cell types in specific regions of the human nervous system. The intracerebral formation of abnormal proteinaceous Lewy bodies and Lewy neurites begins at defined induction sites and advances in a topographically predictable sequence. As the disease progresses, components of the autonomic, limbic, and somatomotor systems become particularly badly damaged. During presymptomatic stages 1-2, inclusion body pathology is confined to the medulla oblongata/pontine tegmentum and olfactory bulb/anterior olfactory nucleus. In stages 3-4, the substantia nigra and other nuclear grays of the midbrain and forebrain become the focus of initially slight and, then, severe pathological changes. At this point, most individuals probably cross the threshold to the symptomatic phase of the illness. In the end-stages 5-6, the process enters the mature neocortex, and the disease manifests itself in all of its clinical dimensions.
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            Association of olfactory dysfunction with risk for future Parkinson's disease.

            Although olfactory dysfunction is commonly associated with Parkinson's disease (PD), it is not known whether such dysfunction can predate the onset of clinical PD in a community-based population. This study examines the association of olfactory dysfunction with future development of PD in Honolulu-Asia Aging Study cohort members Olfaction was assessed from 1991 to 1996 in 2,267 men in the Honolulu-Asia Aging Study aged 71 to 95 years who were free of clinical PD and dementia at the time of olfaction testing. Participants were followed for up to 8 years for incident PD RESULTS: In the course of follow-up, 35 men were diagnosed with PD (24.6/10,000 person-years). The average age at the time of diagnosis was 82.9 +/- 3.8 (range, 76-93) years, and the average time to a diagnosis was 4.0 +/- 1.9 (range, 1-8) years. During the first 4 years of follow-up, age-adjusted incidence of PD declined from 54.5/10,000 person-years in the lowest quartile of odor identification to 26.6, 8.2, and 8.4/10,000 person-years in the second, third, and fourth quartiles, respectively (p < 0.001 for trend). After adjustment for age and other potential confounders, the odds ratios for PD in the lowest quartile was 5.2 (95% confidence interval, 1.5-25.6) compared with the top two quartiles. This relation was not evident beyond 4 years of follow-up. Impaired olfaction can predate clinical PD in men by at least 4 years and may be a useful screening tool to detect those at high risk for development of PD in later life.
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              The influences of age on olfaction: a review

              Decreased olfactory function is very common in the older population, being present in over half of those between the ages of 65 and 80 years and in over three quarters of those over the age of 80 years. Such dysfunction significantly influences physical well-being and quality of life, nutrition, the enjoyment of food, as well as everyday safety. Indeed a disproportionate number of the elderly die in accident gas poisonings each year. As described in this review, multiple factors contribute to such age-related loss, including altered nasal engorgement, increased propensity for nasal disease, cumulative damage to the olfactory epithelium from viral and other environmental insults, decrements in mucosal metabolizing enzymes, ossification of cribriform plate foramina, loss of selectivity of receptor cells to odorants, changes in neurotransmitter and neuromodulator systems, and neuronal expression of aberrant proteins associated with neurodegenerative disease. It is now well established that decreased smell loss can be an early sign of such neurodegenerative diseases as Alzheimer's disease and sporadic Parkinson's disease. In this review we provide an overview of the anatomy and physiology of the aging olfactory system, how this system is clinically evaluated, and the multiple pathophysiological factors that are associated with its dysfunction.
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                Author and article information

                Contributors
                Journal
                Front Aging Neurosci
                Front Aging Neurosci
                Front. Aging Neurosci.
                Frontiers in Aging Neuroscience
                Frontiers Media S.A.
                1663-4365
                07 July 2020
                2020
                : 12
                : 208
                Affiliations
                Department of Otolaryngology—Head and Neck Surgery, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo , Tokyo, Japan
                Author notes

                Edited by: Atsushi Takeda, Sendai Nishitaga National Hospital, Japan

                Reviewed by: Mutsumi Iijima, Tokyo Women’s Medical University, Japan; Philipp Mahlknecht, Innsbruck Medical University, Austria

                *Correspondence: Kenji Kondo kondok-tky@ 123456umin.ac.jp
                Article
                10.3389/fnagi.2020.00208
                7358644
                32733233
                c177a4aa-d022-4ba9-aa5d-a4078b4ee406
                Copyright © 2020 Kondo, Kikuta, Ueha, Suzukawa and Yamasoba.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 April 2020
                : 12 June 2020
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 214, Pages: 16, Words: 14488
                Funding
                Funded by: Ministry of Education, Culture, Sports, Science and Technology 10.13039/501100001700
                Categories
                Neuroscience
                Review

                Neurosciences
                aging,olfactory receptor neurons,basal cells,regeneration,olfactory bulb,olfactory cortex,neurodegenerative diseases

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