xRead - Olfactory Disorders (September 2023)

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INTERNATIONAL CONSENSUS ON OLFACTION

13.9% to 50% of individuals > 65 years and up to 80% in those > 80years. 114,122,125,133,522–524 Longitudinal studies have sup ported the findings of cross-sectional studies with one cit ing an overall 5-year incidence of developing OD in 12.5% of previously normosmic older adults, ranging from 4.1% in those aged 53 to 59 years and up to 47.1% in those aged 80 to 97 years. 521 Specific risk factors appear to be involved in decreased olfaction, including male sex, con current sinonasal disorders, smoking, alcohol abuse, obe sity, low socioeconomic status, minority status, and care giver dependency, while other factors appear protective, such as regular exercise. 521,525–528 Initial improvement in olfactory ability through child hood is followed by deterioration in later adulthood, possibly because odor identification requires both detec tion and cognitive processing with associated discrimi nation, recognition, and name retrieval. Odor identifica tion in children < 10 years is worse than teenagers and adults, likely related to either underdeveloped cognitive processing or difficulty in testing methodology in this age group, and improves through the second decade of life. 529,530 While some studies have suggested that odor detection thresholds and overall olfactory ability remain relatively stable from childhood through late adulthood, partly as a result of increased odor familiarity over time, most research has identified age as the most consis tently proven risk factor for smell loss, with optimal olfactory performance in the third to fourth decade of life followed by slow steady deterioration that acceler ates after age 60 years and becomes particularly severe after age 70 to 80 years. 125,128,130,134,33,333,524,529–535 Notably, 5-year mortality rates in these hyposmic elderly individu als has been found to be as much as 36% higher compared with their normosmic counterparts, highlighting clinical significance. 73,122,522 Several underlying pathophysiologic mechanisms have been proposed to explain the association between age and olfaction. Odor identification requires both peripheral sensory perception as well as central cognitive processing, and insults at any point along the pathway may compro mise olfaction. Possible mechanisms associated with the olfactory neuroepithelium include age-related atrophy; cumulative exposure to pollution, toxins, and bacteria; decrease in mucosal blood flow; chronic inflammation; impaired mucociliary function; decreased regenera tive capacity; replacement with respiratory epithelium; decrease in the number and specificity of ORs; reduction in the size and number of patent foramina in the cribriform plate; impairment of immunologic and enzymatic defense mechanisms; and cellular accumulation of amyloid and tau filaments. 522,525,536–538 The OB may demonstrate atrophy, loss of neuronal elements, and decreased laminae and glomeruli with age, as well as accumulation of tau and α -synuclein. 522,525,539,540 At higher-level processing

centers, olfactory loss may be associated with age-related cortical degeneration, specifically reduction in the volume or function of the hippocampus, amygdala, piriform cortex, OFC, anterior olfactory sulcus, and cholinergic system. 522,525,527,541 Some studies suggest a decline in the trigeminal contribution to olfaction may play a role, although this is unconfirmed. 527 Genetic predispositions exist for age-related hyposmia, including the val66met polymorphism of brain-derived neurotrophic factor and the ε 4-allele of human apolipoprotein E gene. 522 Despite the contribution of genetics, which has been shown to influence the intensity and perception of olfaction, twin studies suggest that environmental factors likely contribute to a greater degree than genetic factors with increased age. 538,542 While broad age-related trends are well-established, significant heterogeneity exists between study findings because of variation in study populations, olfactory instruments, and classification of dysfunction. Studies sometimes designate dysfunction based on normative age-specific cutoffs rather than ideal levels, limiting comparison. 134 Subjective self-assessment yields a much lower prevalence than objective testing, indicating a signif icant lack of sensitivity in relying on patient report alone, with up to 75% of patients not recognizing their own smell loss. 11,33,122,125,128,522,527,543 Sensitivity can be improved by querying specifically about age-related changes in smell function. 121 Given the risks associated with smell loss and the wide prevalence despite lack of recognition, consideration may be given for brief testing to screen for severe dysfunc tion in aging individuals. Consensus in standardized objec tive olfactory instruments and definitions of dysfunction should be sought to more effectively compare outcomes and share knowledge of this common and important problem. Increasing age after the fourth decade is associated with decreasing OF. Aggregate grade of evidence : B (Level 1: two studies; Level 2: 27 studies). J Related to neurodegenerative disease Over the past decade, multiple studies have demonstrated that OD may be the earliest sign of neurodegeneration, affecting those with subjective cognitive decline, mild cog nitive impairment (MCI), AD, and Parkinson disease (PD). In preclinical AD, patients can experience sub jective cognitive decline that causes them concern, although classic neuropsychological tests are not able to detect any change in cognition at this time. 13,132,406–416, 418,419,421–426,429–431,544–850 A meta-analysis of five studies