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Objective: Olfactory dysfunction is a "canary in the coalmine" for aging conditions. We evaluated olfactory dysfunction as a biomarker of early frailty in older adults living in the United States., Study Design: Prospective, longitudinal, nationally representative study., Setting: National Social Life, Health and Aging Project (NSHAP)., Methods: We examined data from 1061 community-dwelling older US adults. Odor identification (5-item Sniffin' Stick) and frailty scores were measured at baseline and 5-year follow-up. Multivariate logistic regressions evaluated the association between olfactory dysfunction and frailty at baseline in cross-section and over time in the transition from robust to prefrail to frail, adjusting for confounding factors measured at baseline., Results: Older US adults who were anosmic at baseline were more likely to be frail 5 years later compared to normosmic peers (odds ratio [OR]: 3.83, 95% confidence interval [CI]: 1.10-13.31, P = .035). Examining changes in frailty stage over time, we found that anosmics were more likely to transition from prefrail to frail over 5 years (OR: 3.25, 95% CI: 1.31-8.08, P = .011). Interestingly, hyposmics did not show a similar trajectory toward frailty (P > .05). In contrast, olfactory dysfunction was not associated with frailty in cross-section (OR: 0.90, 95% CI: 0.43-1.89, P = .787, hyposmia; OR: 0.72, 95% CI: 0.15-3.35, P = .673, anosmia)., Conclusion: Older US adults with anosmia face higher odds of becoming frail over 5 years, especially those in the prefrail stage. Olfactory dysfunction may serve as a surrogate marker for early-stage neurodegenerative diseases, which are strong contributors to frailty., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: Sleep-disordered breathing (SDB) is a common, underdiagnosed condition in older adults with major health consequences, including disrupted central nervous system functioning. Whether SDB may affect sensory function is unclear. We sought to address this question by comparing 2 forms of olfactory testing which measure peripheral and central olfactory processing., Methods: We assessed SDB (survey-reported snoring frequency, nighttime apneic events, or diagnosis of sleep apnea) in the National Social Life, Health, and Aging Project, a nationally representative sample of older U.S. adults. Odor sensitivity (peripheral) and odor identification (central) were assessed with validated instruments. Logistic regression was used to test the relationship between SDB and olfaction, accounting for relevant covariates, including demographics, cognition, and comorbidity., Results: Twenty-nine percent of older U.S. adults reported symptoms of SDB (apneic events or nightly snoring). Of these, only 32% had been diagnosed with sleep apnea. Older adults with SDB (those who reported symptoms or have been diagnosed with sleep apnea) were significantly more likely to have impaired odor identification (odds ratio 2.13, 95% confidence interval 1.19-3.83, p = .012) in analyses that accounted for age, gender, race/ethnicity, education, cognition, comorbidities (including depression), and body mass index. Presence of SDB was not associated with impaired odor sensitivity (odds ratio 1.03, 95% confidence interval 0.75-1.43, p = .84)., Conclusion: SDB is highly prevalent but underdiagnosed in older U.S. adults and is associated with impaired odor identification but not odor sensitivity. These data support the concept that SDB affects pathways in the central nervous system which involve chemosensory processing., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Neuroanatomic connections link the olfactory and limbic systems potentially explaining an association between olfactory dysfunction and depression. Some previous studies have demonstrated that olfactory dysfunction is associated with increased depressive symptoms. However, these studies were cross-sectional and unable to establish which develops first. We used longitudinal data to determine if impaired odor identification increased subsequent depressive symptoms or vice versa. We assessed olfaction and depression in the National Social Life, Health, and Aging Project, a nationally representative, 15-year longitudinal study of older US adults. Olfaction was measured using a validated odor identification test (Sniffin' Sticks). Depressive symptoms were measured using a modified version of the validated Center for Epidemiological Studies Depression Scale. Multivariable logistic regression models examined the temporal relationships between developing olfactory dysfunction and depression while accounting for demographics, disease comorbidities, alcohol use, smoking, and cognition. Older adults with olfactory dysfunction had concurrent frequent depressive symptoms (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.00-1.43). Among healthy adults at baseline, those who had olfactory dysfunction were more likely to develop frequent depressive symptoms 5 or 10 years later (OR = 2.22, 95% CI = 1.13-4.37). Conversely, those with frequent depressive symptoms at baseline were not more likely to develop olfactory dysfunction 5 or 10 years later. We show for the first time that olfactory dysfunction predicts subsequent development of depression in older US adults. These data support screening for depression in older adults with chemosensory impairment and set the stage for disentangling the relationship between olfaction and depression., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Inflammation has been implicated in physical frailty, but its role in sensory impairment is unclear. Given that olfactory impairment predicts dementia and mortality, determining the role of the immune system in olfactory dysfunction would provide insights mechanisms of neurosensory decline. We analyzed data from the National Social Life, Health and Aging Project, a representative sample of home-dwelling older US adults. Plasma levels of 18 cytokines were measured using standard protocols (Luminex xMAP). Olfactory function was assessed with validated tools (n-butanol sensitivity and odor identification, each via Sniffin' Sticks). We tested the association between cytokine profiles and olfactory function using multivariate ordinal logistic regression, adjusting for age, gender, race/ethnicity, education level, cognitive function, smoking status, and comorbidity. Older adults with the IL-1Rahigh-IL-4low-IL-13low cytokine profile had worse n-butanol odor sensitivity (odds ratio [OR] = 1.61, 95% confidence interval [CI] 1.19-2.17) and worse odor identification (OR = 1.42, 95% CI 1.11-1.80). Proinflammatory, Th1, or Th2 cytokine profiles were not associated with olfactory function. Moreover, accounting for physical frailty did not alter the main findings. In conclusion, we identified a plasma cytokine signature-IL-1Rahigh-IL-4low-IL-13low-that is associated with olfactory dysfunction in older US adults. These data implicate systemic inflammation in age-related olfactory dysfunction and support a role for immune mechanisms in this process, a concept that warrants additional scrutiny., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Olfaction plays a critical role in health and function in older adults, and impaired sense of smell is a strong predictor of morbidity and mortality. Smoking cigarettes causes olfactory impairment, but the mechanism of damage and ability to recover after cessation are unknown. We investigated the relationship between time since quitting and olfactory dysfunction in order to elucidate the mechanism(s) by which smoking damages the olfactory system and to inform patient counseling., Methods: Using longitudinal data from the National Social Life Health and Aging Project (n = 3528 older adults, including 1526 former smokers), we analyzed the association between odor identification performance and time since smoking cessation using multivariate ordinal logistic regression, adjusting for cognition and demographic variables. To test whether vascular disease plays a role, we also assessed the relationship between olfactory decline and incidence of heart attack and heart disease., Results: Former smokers who quit ≤15 years before testing had significantly impaired olfaction compared to never smokers (p = 0.04), but those who quit >15 years prior did not. Olfactory decline over 5 years showed modest evidence toward predicting increased incidence of heart attack or heart disease (p = 0.08)., Conclusion: Olfactory impairment in smokers persists 15 years after quitting, which is consistent with a vascular mechanism of impairment. Indeed, olfactory decline is a predictor of the development of cardiovascular disease. Taken together, these data suggest that olfactory loss may be a useful sign of underlying vascular pathology. Further investigation of olfactory loss as an early biomarker for cardiovascular disease is warranted., (© 2019 ARS-AAOA, LLC.)

Objectives: To investigate the relationship between olfactory dysfunction and subsequent diagnosis of dementia., Design: Longitudinal study of a population representative of U.S. older adults., Setting: Home interviews (National Social Life, Health, and Aging Project)., Participants: Men and women aged 57 to 85 (N = 2,906)., Measurements: Objective odor identification ability was measured at baseline using a validated five-item test. Five years later, the respondent, or a proxy if the respondent was too sick to interview or had died, reported physician diagnosis of dementia. The association between baseline olfactory dysfunction and an interval dementia diagnosis was tested using multivariate logistic regression, controlling for age, sex, race and ethnicity, education, comorbidities (modified Charlson Comorbidity Index), and cognition at baseline (Short Portable Mental Status Questionnaire)., Results: Older adults with olfactory dysfunction had more than twice the odds of having developed dementia 5 years later (odds ratio = 2.13, 95% confidence interval = 1.32-3.43), controlling for the above covariates. Having more odor identification errors was associated with greater probability of an interval dementia diagnosis (P = .04, 1-degree of freedom linear-trend test)., Conclusion: We show for the first time in a nationally representative sample that home-dwelling older adults with normal cognition and difficulty identifying odors face higher odds of being diagnosed with dementia 5 years later, independent of other significant risk factors. This validated five-item odor identification test is an efficient, low-cost component of the physical examination that can provide useful information while assessing individuals' risk of dementia. Use of such testing may provide an opportunity for early interventions to reduce the attendant morbidity and public health burden of dementia., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

Objectives/hypothesis: A systematic review and meta-analysis of the literature was undertaken, examining the association between tobacco smoking and olfactory function in humans, utilizing PubMed and Web of Science (1970-2015) as data sources., Study Design: Systematic literature review and meta-analysis., Methods: This database review of studies of smoking and olfaction, with a focus on identifying high-quality studies (based on modified versions of the Newcastle-Ottawa Scale), used validated olfactory tests among the generally healthy population., Results: We identified 11 studies meeting inclusion criteria. Of 10 cross-sectional studies, two were excluded from meta-analysis because the cohorts they studied were included in another article in the review. In meta-analysis, current smokers had substantially higher odds of olfactory dysfunction compared to never smokers (odds ratio [OR] = 1.59, 95% confidence interval [CI] = 1.37-1.85). In contrast, former smokers were found to have no difference in risk of impaired olfaction compared to never smokers (OR = 1.05, 95% CI = 0.91-1.21). The single longitudinal study reviewed found a trend toward increased risk of olfactory decline over time in ever smokers; this trend was stronger in current as compared to former smokers., Conclusions: Current smoking, but not former smoking, is associated with significantly increased risk of olfactory dysfunction, suggesting that the effects of smoking on olfaction may be reversible. Future studies that prospectively evaluate the impact of smoking cessation on improvement in olfactory function are warranted., Level of Evidence: N/A. Laryngoscope, 127:1753-1761, 2017., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Self-reported olfactory function has poor sensitivity (i.e., people with measured olfactory dysfunction are unlikely to accurately report it). We aimed to identify factors associated with lack of awareness of smell dysfunction. Objective odor identification was evaluated using a validated 5-item test in respondents from the National Social Life, Health, and Aging Project, a representative sample of home-dwelling, US adults ages 57-85 (n = 1468). Self-reported olfaction was assessed with a 5-point Likert scale. Using multivariate logistic regression, we tested factors that might influence inaccuracy of self-reported olfaction, including age, gender, race/ethnicity, education, marital status, cognition, comorbidity, smoking, depression, anxiety, self-rated mental and physical health, and social activity. Among older US adults, 12.4% reported their sense of smell as fair or poor, while 22.0% had objective olfactory dysfunction (≤3 items correct out of 5). Among those with measured olfactory dysfunction, 74.2% did not recognize it; these individuals were more likely to be older, Black, never married, and to have worse cognitive function compared to individuals who recognized their dysfunction (P < 0.05, all). Individuals who lacked awareness of their olfactory dysfunction had the greatest cognitive impairment at 5-year follow-up, followed by individuals aware of their dysfunction and finally normosmics (P < 0.001). Older Americans with measured olfactory dysfunction are unlikely to report it, and those who lack awareness of this dysfunction have distinct demographic, social, and cognitive characteristics. Therefore, clinicians should objectively test patients. Individuals who lack awareness of their olfactory dysfunction have poor cognitive outcomes and should receive additional clinical scrutiny., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Olfactory dysfunction has profound effects on quality of life, physical and social function, and mortality itself. Nitrogen dioxide (NO 2 ) is a pervasive air pollutant that is associated with respiratory diseases. Given the olfactory nerve's anatomic exposure to airborne pollutants, we investigated the relationship between NO 2 exposure and olfactory dysfunction., Methods: The ability to identify odors was evaluated using a validated test in respondents from the National Social Life, Health, and Aging Project (NSHAP), a representative probability sample of home-dwelling, older U.S. adults age 57 to 85 years. Exposure to NO 2 pollution was assessed using measurements obtained from the U.S. Environmental Protection Agency (EPA) Aerometric Information Retrieval System (AIRS) ambient monitoring site closest to each respondent's home. We tested the association between NO 2 exposure and olfactory dysfunction using multivariate logistic regression., Results: Among older adults in the United States, 22.6% had impaired olfactory function, defined as ≤3 correct (out of 5) on the odor identification test. Median NO 2 exposure during the 365 days prior to the interview date was 14.7 ppb (interquartile range [IQR], 10.8 to 19.7 ppb). An IQR increase in NO 2 exposure was associated with increased odds of olfactory dysfunction (OR, 1.35; 95% CI, 1.07 to 1.72), adjusting for age, gender, race/ethnicity, education, cognition, comorbidity, smoking, and season of the home interview (n = 1823)., Conclusion: We show for the first time that NO 2 exposure is associated with olfactory dysfunction in older U.S. adults. These results suggest an important role for NO 2 exposure on olfactory dysfunction, and, potentially, nasal disease more broadly., (© 2016 ARS-AAOA, LLC.)

Objectives: The olfactory nerve is anatomically susceptible to injury from pollution in inspired air, but there are no large-scale epidemiologic studies investigating this relationship., Methods: Cross-sectional study using data from the National Social Life, Health, and Aging Project, a representative sample of home-dwelling US adults age 57-85 years. Olfactory function was tested using a validated 5-item odor identification test (Sniffin' Sticks). Exposure to fine particulate matter (PM 2.5 ) at each respondent's home was estimated as 1-12 month moving averages prior to olfactory assessment using validated spatio-temporal models., Results: Olfactory dysfunction was significantly associated with PM 2.5 exposures averaged over 3-12 months in urban-dwelling respondents. The strongest effect was for 6 month average exposure (per 1-IQR increase in PM 2.5 : OR 1.28, 95% CI 1.05, 1.55) adjusting for age, gender, race/ethnicity, education, cognition, comorbidity, smoking, and the season. Interestingly, the most deleterious effects were observed among the youngest respondents, 57-64 years old, and those living in the northeast and south., Conclusions: We show for the first time that air pollution exposure is associated with poor olfaction among urban-living, older US adults., (Copyright © 2016. Published by Elsevier Inc.)

Olfactory dysfunction is a common complaint among physician visits. Olfactory loss affects quality of life and impairs function and activities of daily living. The purpose of our study was to assess the degree of odor identification associated with mental health. Olfactory function was measured using the brief smell identification test. Depressive symptoms were measured by the Center for Epidemiologic Studies Depression scale. Loneliness was assessed by the de Jong-Gierveld Loneliness Scale. Cognition was measured by a battery of 19 cognitive tests. The frequency of olfactory dysfunction in our study was ~40%. Older subjects had worse olfactory performance, as previously found. More loneliness was associated with worse odor identification. Similarly, symptoms of depression were associated with worse olfaction (among men). Although better global cognitive function was strongly associated with better odor identification, after controlling for multiple factors, the associations with depression and loneliness were unchanged. Clinicians should assess these mental health conditions when treating older patients who present with olfactory deficits., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Age-related olfactory loss (presbyosmia) is a prevalent sensory impairment with a large public health impact. In cross-sectional analyses, we found striking health disparities in olfactory function among older U.S. adults. Here, we report a 5-year follow-up to determine the magnitude of within-person olfactory decline., Methods: The National Social Life, Health, and Aging Project (NSHAP) interviewed a probability sample of home-dwelling older U.S. adults (57-85 years) in 2005-2006 (Wave 1) and reinterviewed them in 2010-2011 (Wave 2), assessing demographics, social life, and health, including olfaction. Odor identification was measured with a 5-item version of the Sniffin' Sticks (0-5 correct). Fourteen hundred and thirty-six respondents provided olfaction data in both waves. Multivariate linear and logistic regression were used to model the association between change in olfactory performance and demographic, health, and psychosocial factors., Results: Odor identification declined most rapidly among older individuals (0.25 additional errors per 5 years for each decade of age, p < .001) and in men (0.17 additional errors per 5 years compared to women, p = .005). Among those with perfect scores in Wave 1, African Americans declined more rapidly than Whites (p = .04). Neither socioeconomic status, health conditions, cognition, mental health, alcohol use nor smoking was associated with change in olfaction (p > .05, all)., Conclusions: The rate of olfactory decline increases with age and is greater among men than women despite adjusting for differences in psychosocial and health conditions, indicating physiologic factors as drivers. African Americans are more likely to experience initial olfactory decline, consistent with an earlier onset of aging among this subgroup., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Prediction of mortality has focused on disease and frailty, although antecedent biomarkers may herald broad physiological decline. Olfaction, an ancestral chemical system, is a strong candidate biomarker because it is linked to diverse physiological processes. We sought to determine if olfactory dysfunction is a harbinger of 5-year mortality in the National Social Life, Health and Aging Project [NSHAP], a nationally representative sample of older U.S. adults. 3,005 community-dwelling adults aged 57-85 were studied in 2005-6 (Wave 1) and their mortality determined in 2010-11 (Wave 2). Olfactory dysfunction, determined objectively at Wave 1, was used to estimate the odds of 5-year, all cause mortality via logistic regression, controlling for demographics and health factors. Mortality for anosmic older adults was four times that of normosmic individuals while hyposmic individuals had intermediate mortality (p<0.001), a "dose-dependent" effect present across the age range. In a comprehensive model that included potential confounding factors, anosmic older adults had over three times the odds of death compared to normosmic individuals (OR, 3.37 [95%CI 2.04, 5.57]), higher than and independent of known leading causes of death, and did not result from the following mechanisms: nutrition, cognitive function, mental health, smoking and alcohol abuse or frailty. Olfactory function is thus one of the strongest predictors of 5-year mortality and may serve as a bellwether for slowed cellular regeneration or as a marker of cumulative toxic environmental exposures. This finding provides clues for pinpointing an underlying mechanism related to a fundamental component of the aging process.

Background: Age-related olfactory loss (presbyosmia) substantially decreases quality of life, presages neurodegenerative disease, impairs nutrition, and predicts mortality. We sought to determine how race is associated with olfactory loss in older American adults in order to inform both health care and policy., Methods: The National Social Life, Health and Aging Project interviewed a cross-sectional nationally representative probability sample of older adults in the United States. African Americans and Hispanics were oversampled, providing power to detect disparities for these subgroups. As part of an omnibus survey of demographic, social, psychological, and biological measures, National Social Life, Health and Aging Project assessed the ability to verbally identify odors by presenting five odor pens. Multivariate ordinal logistic regression quantified racial differences in odor identification, and then tested potential confounders., Results: African Americans and Hispanics had markedly worse olfactory function (controlling for gender and age) compared with whites (p < .001), twice the magnitude of gender differences, and comparable to aging 9 years. Cognition, household assets, and education accounted for the disparity found among Hispanics but not among African Americans. Moreover, other potential confounders, such as physical or mental health, including tobacco and alcohol use, did not account for the African American health disparity, which remained significant (p = .001) after including these factors., Conclusions: African Americans are more likely to suffer from presbyosmia, a health disparity not explained by gender, education, cognition, physical or mental health, and health behaviors. This novel health disparity may result from lifetime environmental exposures, diet, or genetic susceptibility. Dissecting the interactions among these putative mechanisms will provide insight into ameliorating this decline in critical human sensory function.