Prediabetes Progression and Reversion: Social Factors and Racial/Ethnic Differences.

OBJECTIVE: Racial and ethnic minorities are disproportionately affected by diabetes. Social characteristics, such as family structure, social support, and loneliness, may contribute to these health disparities. In a nationally representative sample of diverse older adults, we evaluated longitudinal rates of both progression from prediabetes to diabetes and reversion from prediabetes to normoglycemia. RESEARCH DESIGN AND METHODS: Using the longitudinal Health and Retirement Study (2006-2014), our sample included 2625 follow-up intervals with a prediabetes baseline (provided by 2229 individuals). We analyzed 4-year progression and reversion rates using HbA1c and reported presence or absence of physician-diagnosed diabetes. We utilized chi-square and logistic regression models to determine how race/ethnicity and social variables influenced progression or reversion controlling for comorbidities and demographics. RESULTS: Overall, progression to diabetes was less common than reversion (17% vs. 36%). Compared to Whites, Hispanic/Latino respondents had higher odds of progression to diabetes from prediabetes while Black respondents had lower odds of reversion, adjusting for physical health and demographics. For social variables, Hispanics/Latinos had the highest reliance on and openness with family and the lowest rates of loneliness. The inclusion of social variables in regression models reduced the odds of progression for Hispanics/Latinos but did not alter Black's lower rate of reversion. CONCLUSIONS: Hispanic/Latinos and Blacks not only had different transition pathways leading to diabetes, but also had different social profiles, affecting Hispanic/Latino progression, but not Black reversion. These differences in the influence of social variables on diabetes risk may inform the design of culturally-specific efforts to reduce disparities in diabetes burden.

Examining the Longitudinal Relationship Between Olfactory Dysfunction and Frailty in Community-Dwelling, older US Adults.

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.

Air pollution exposure is associated with rhinitis in older US adults via specific immune mechanisms.

BACKGROUND: Pathophysiology of rhinitis in older adults is largely unknown. We tested whether air pollution is associated with this condition and how immune mechanisms may play a role in this relationship. METHODS: We analyzed cross-sectional data from the National Social Life, Health, and Aging Project, a nationally representative study of older adults born between 1920 and 1947. Particulate matter ≤2.5 µm (PM2.5 ) air pollution exposure estimates were generated using validated spatiotemporal models. Presence of rhinitis was defined based on medication use (≥1: intranasal medications: steroids, antihistamines, lubricants, and/or decongestants, and/or oral medications: antihistamines and/or decongestants). K-means cluster analysis (Jaccard method) was used to group 13 peripheral blood cytokines into 3 clusters to facilitate functional determination. We fitted multivariate logistic regressions to correlate PM2.5 exposure with presence of rhinitis, controlling for confounders, and then determined the role of cytokines in this relationship. RESULTS: Long- (but not short-) term exposure to PM2.5 was associated with presence of rhinitis: 3-year exposure window, odds ratio (OR) = 1.32, 95% confidence interval (CI): 0.98, 1.80, per 1 standard deviation (SD) PM2.5 increase. Inclusion of cytokine cluster in the model led to a modestly stronger effect of PM2.5 exposure on rhinitis (OR = 1.37; 95% CI: 1.00, 1.87; 3-year exposure window). The particular immune profile responsible for this result was composed of elevated IL-3, IL-12, and IFN-γ (OR = 4.86, 95% CI: 1.10, 21.58, immune profile-PM2.5 exposure interaction term). CONCLUSION: We show for the first time that IL-3, IL-12, and IFN-γ explain in part the relationship between PM2.5 exposure and rhinitis in older US adults. If confirmed, these immune pathways may be used as therapeutic targets.

Moderation of associations between weight discrimination and diabetes status by psychosocial factors.

Weight discrimination has adverse effects on health that include increasing the risk factors for developing type 2 diabetes. Preliminary evidence suggests a positive association between weight discrimination and diagnosed diabetes; however, it is unknown whether psychosocial resources may buffer this association. In logistic regressions stratified by gender, we examined links between weight discrimination and diabetes among a nationally representative sample of U.S. adults (the National Social Life, Health, and Aging Project; N = 2,794 adults age 50 and older in 2015-16). We also tested the extent to which trait-resilience and social support from a spouse/partner, family, and friends buffered any observed association. We adjusted for known predictors of diabetes (age, race/ethnicity, Body Mass Index) and conducted sensitivity analyses restricted to men and women with obesity. Net of covariates, in the overall sample, weight discrimination was associated with significantly greater odds of having ever had diabetes among women (OR = 2.00, 95% CI [1.15, 3.47]), but not men. Among women with obesity, weight discrimination was only significantly associated with greater odds of diabetes for those with low resilience (OR = 1.84, 95% CI [1.01, 3.35]). Among men overall, weight discrimination was associated with lower odds of diabetes for those with high family support (OR = 0.03, 95% CI [0.003, 0.25]) as well as those with high friend support (OR = 0.34, 95% CI [0.13, 0.91]); similar effects were observed in men with obesity. These novel findings evince a role for psychosocial resources in buffering associations between weight discrimination and diabetes.

Olfactory decline develops in parallel with frailty in older US adults with obstructive lung diseases.

BACKGROUND: Frailty is prevalent among older adults with asthma or chronic obstructive pulmonary disease (obstructive lung diseases [OLDs]). Frailty and OLD's co-occurrence is associated with increased hospitalization/mortality. Chemosensory dysfunction is closely connected to both OLD and frailty. We evaluated the utility of olfactory decline as a biomarker of frailty in the setting of OLD. METHODS: We performed a prospective, longitudinal, nationally representative study of community-dwelling older US adults in the National Social Life, Health and Aging Project, an omnibus in-home survey. Respondents reported a physician's diagnosis of OLD. Decline in odor identification and sensitivity over 5 years and frailty (adapted fried frailty phenotype criteria) were measured using standard tools. Multivariate logistic regressions evaluated the association between OLD status, olfactory decline, and frailty. RESULTS: We compared individuals with OLD (n = 98; mean age 71.2 years, 59.2% women) and those without OLD (n = 1036; mean age 69.5 years, 58.9% women). Olfactory identification decline was associated with developing frailty over the 5-year follow-up period in individuals with OLD (odds ratio [OR] = 9.1, 95% confidence interval [CI] = 2.1-38.6, p = 0.003). Olfactory decline predicted incidence of frailty in individuals with OLD (identification: OR = 4.8, 95% CI = 1.3-17.5, P = 0.018; sensitivity: OR = 6.1, 95%CI = 1.2-31.0, p = 0.030) but not in those without OLD adjusting for demographics, heavy alcohol use, current smoking, and comorbidity. Results were robust to different thresholds for olfactory decline and frailty development. CONCLUSIONS: Older adults with OLD who experience olfactory decline face higher odds of developing frailty. Use of olfactory decline as a biomarker to identify frailty could allow earlier intervention and decrease adverse outcomes for high-risk older adults with OLD.

Association of APOE ε4 Status With Long-term Declines in Odor Sensitivity, Odor Identification, and Cognition in Older US Adults.

BACKGROUND AND OBJECTIVES: The APOE ε4 allele confers susceptibility to faster decline in odor identification and subsequently to Alzheimer disease (AD). Odor identification requires recognizing and naming odors and detecting them (odor sensitivity). Whether APOE ε4 is associated with decline of odor sensitivity and whether such decline serves as a harbinger of cognitive decline and AD remains unclear. We determined whether and when APOE ε4 affects decline in odor sensitivity, odor identification, and cognition in the National Social Life Health and Aging Project (NSHAP). METHODS: We used data from NSHAP, a nationally representative survey study of home-dwelling US older adults. Olfaction was measured over time (odor identification in 2005, 2010, and 2015; odor sensitivity in 2010 and 2015; both using validated tests). Cognition was measured with a modified version of the Montreal Cognitive Assessment in 2010 and 2015. Genotyping was performed using DNA samples collected in 2010. Odor sensitivity and identification were compared among APOE ε4 carriers and noncarriers stratified by age. Relationships between APOE ε4, odor sensitivity, odor identification, and cognition were analyzed in cross-section using ordinal logistic regression and longitudinally using mixed-effects models adjusted for confounders. RESULTS: Odor sensitivity was measured in 865 respondents, odor identification in 1,156 respondents, and cognition in 864 respondents; all these respondents had genetic data available. Odor sensitivity deficits in APOE ε4 carriers were apparent at ages 65-69 years, whereas odor identification deficits did not appear until ages 75-79 years. Subsequently, odor sensitivity did not decline more rapidly with aging in APOE ε4 carriers compared with that in noncarriers (carrier status and aging interaction: odds ratio [OR] 1.44, 95% CI 0.94-2.19, p = 0.092), whereas odor identification declined more rapidly in carriers (aging 10 years interaction: OR 0.26, 95% CI 0.13-0.52, p < 0.001). As expected, and in parallel to odor identification, cognition declined more rapidly in APOE ε4 carriers (interaction: OR 0.55, 95% CI 0.34-0.89, p = 0.015). DISCUSSION: APOE ε4 affects decline of odor sensitivity earlier than odor identification or cognition. Thus, testing odor sensitivity may be useful to predict future impaired cognitive function. Identifying the mechanism underlying these relationships will elucidate the key role of olfaction in neurodegeneration during aging.

Assessing how Age, Sex, Race, and Education Affect the Relationships Between Cognitive Domains and Odor Identification.

BACKGROUND: The associations between cognitive domains and odor identification are well established, but how sociodemographic variables affect these relationships is less clear. PURPOSE: Using the survey-adapted Montreal Cognitive Assessment instrument (MoCA-SA), we assess how age, sex, race, and education shape these relationships. METHODS: We first used cluster analysis and multidimensional scaling to empirically derive distinct cognitive domains from the MoCA-SA as it is unclear whether the MoCA-SA can be disaggregated into cognitive domains. We then used ordinal logistic regression to test whether these empirically derived cognitive domains were associated with odor identification and how sociodemographic variables modified these relationships. STUDY POPULATION: Nationally representative sample of community-dwelling US older adults. RESULTS: We identified 5 out of the 6 theoretical cognitive domains, with the language domain unable to be identified. Odor identification was associated with episodic memory, visuospatial ability, and executive function. Stratified analyses by sociodemographic variables reveal that the associations between some of the cognitive domains and odor identification varied by age, sex, or race, but not by education. CONCLUSIONS: These results suggest that (1) the MoCA-SA can be used to identify cognitive domains in survey research and (2) the performance of smell tests as a screener for cognitive decline may potentially be weaker in certain subpopulations.

Androstadienone sensitivity is associated with attention to emotions, social interactions, and sexual behavior in older U.S. adults.

Δ 4,16-androstadien-3-one (androstadienone) is a putative human pheromone often linked to sexual attraction in young adults, although specific associations with sexual behavior are not yet established. Androstadienone also serves a broader social-emotional function beyond the sexual domain, specifically tuning the brain to efficiently process emotional information. Whether these effects persist throughout the lifespan into post-reproductive life is unknown. In a laboratory study of older adults, those with greater androstadienone odor sensitivity paid greater attention to subliminal emotional information, specifically, angry faces (p = 0.05), with a similar relationship to happy faces. In contrast, the physical odor n-butanol (a control) did not affect emotional attention (p = 0.49). We then extended this laboratory research and determined whether sensitivity to androstadienone affects the everyday lives of older adults by measuring their social and sexual behavior. In this second study, we surveyed in a nationally representative sample of US older adults living in their homes (National Social Life and Aging Project, 62-90 years; n = 2,086), along with their sensitivity to androstadienone, general olfactory function, health and demographics. Greater sensitivity to androstadienone was associated with richer social lives: having more friends, increased communication with close friends and family, and more participation in organized social events and volunteer activities (all p's ≤ 0.05, generalized linear models, adjusted for age and gender). It was also associated with more recent sexual activity, more frequent sexual thoughts, and viewing sex as an important part of life (all p's ≤ 0.05). General olfactory function did not explain these associations, supporting a specialized function for this pheromone during everyday life, and expanding its role to social life as well as sexual behavior, likely mediated by enhanced attention to emotional information.

Can Digital Communication Protect Against Depression for Older Adults With Hearing and Vision Impairment During COVID-19?

OBJECTIVES: During social isolation imposed by the coronavirus disease 2019 (COVID-19) pandemic, older adults with impaired hearing and vision potentially experienced more communication challenges, increasing their risk for poor mental health. Digital communication (e.g., video calls, e-mail/text/social media) may alleviate in-person isolation and protect against depression. We addressed this question using data from the National Social Life, Health, and Aging Project, a nationally representative panel study of community-dwelling older adults. METHOD: Two thousand five hundred fifty-eight adults aged 55 and older comprised the analytic sample. Interviewer rating at baseline (2015-2016) classified those with vision impairment (VI) or hearing impairment (HI). Olfactory impairment (OI) was measured by objective testing. During COVID-19 (2020-2021), respondents reported how often they contacted nonhousehold family or friends and whether this was by phone, e-mail/text/social media, video, or in-person. They also quantified the frequency of depressive feelings. RESULTS: Older adults with VI or HI but not OI at baseline were significantly less likely to report regular use of video calling and e-mail/text/social media during the pandemic compared to those without impairment. Sensory impairments did not affect the frequency of phone or in-person communication. Adults with VI or HI were more likely to experience frequent depressive feelings during COVID-19. Video calls mitigated this negative effect of VI- and HI-associated depressive feelings in a dose-dependent manner. DISCUSSION: Among communication modalities, video calling had a protective effect against depressive feelings for people with sensory impairment during social isolation. Improving access to and usability of video communication for older adults with sensory impairment could be a strategy to improve their mental health.

Rapid olfactory decline during aging predicts dementia and GMV loss in AD brain regions.

INTRODUCTION: Longitudinal multivariable analyses are needed to determine if the rate of olfactory decline during normal cognition predicts subsequent Alzheimer's disease (AD) diagnoses and brain dysmorphology. METHODS: Older adults (n = 515) were assessed annually for odor identification, cognitive function and dementia clinical diagnosis (max follow-up 18 years). Regional gray matter volumes (GMV) were quantified (3T MRI) in a cross-sectional subsample (n = 121). Regression models were adjusted for APOE-ε4 genotype, dementia risk factors and demographics. RESULTS: Faster olfactory decline during periods of normal cognition predicted higher incidence of subsequent MCI or dementia (OR 1.89, 95% CI: 1.26, 2.90, p < 0.01; comparable to carrying an APOE-ε4 allele) and smaller GMV in AD and olfactory regions (ß = -0.11, 95% CI -0.21, -0.00). DISCUSSION: Rapid olfactory decline during normal cognition, using repeated olfactory measurement, predicted subsequent cognitive impairment, dementia, and smaller GMVs, highlighting its potential as a simple biomarker for early AD detection. HIGHLIGHTS: Rate of olfactory decline was calculated from olfactory testing over ≥3 time points. Rapid olfactory decline predicted impaired cognition and higher risk of dementia. Neurodegeneration on 3T magnetic resonance imaging was identical in those with olfactory decline and Alzheimer's disease.

Beyond the Lung: Geriatric Conditions Afflict Community-Dwelling Older Adults With Self-Reported Chronic Obstructive Pulmonary Disease.

RATIONALE: Chronic obstructive pulmonary disease (COPD) predominantly affects older adults. However, the co-morbid occurrence of geriatric conditions has been understudied. OBJECTIVE: Characterize the prevalence of geriatric conditions among community-dwelling U.S. older adults with self-reported COPD. METHODS: We conducted a nationally representative, cross-sectional study of 3,005 U.S. community-dwelling older adults (ages 57-85 years) from the National Social Life, Health, and Aging Project (NSHAP). We evaluated the prevalence of select geriatric conditions (multimorbidity, functional disability, impaired physical function, low physical activity, modified frailty assessment, falls, polypharmacy, and urinary incontinence) and psychosocial measures (frequency of socializing, sexual activity in the last year, loneliness, cognitive impairment, and depressive symptoms) among individuals with self-reported COPD as compared to those without. Using multivariate logistic and linear regressions, we investigated the relationships between COPD and these geriatric physical and psychosocial conditions. MAIN RESULTS: Self-reported COPD prevalence was 10.7%, similar to previous epidemiological studies. Individuals with COPD had more multimorbidity [modified Charlson score 2.6 (SD 1.9) vs. 1.6 (SD 1.6)], more functional disability (58.1 vs. 29.6%; adjusted OR 3.1, 95% CI 2.3, 4.3), falls in the last year (28.4 vs. 20.8%; adjusted OR 1.4, 95% CI 1.01, 2.0), impaired physical function (75.8 vs. 56.6%; adjusted OR 2.1, 95% CI 1.1, 3.7), more frequently reported extreme low physical activity (18.7 vs. 8.1%; adjusted OR 2.3, 95% CI 1.5, 3.5) and higher frailty prevalence (16.0 vs. 2.7%; adjusted OR 6.3, 95% CI 3.0,13.0) than those without COPD. They experienced more severe polypharmacy (≥10 medications, 37.5 vs. 16.1%; adjusted OR 2.9, 95% CI 2.0, 4.2). They more frequently reported extreme social disengagement and were lonelier, but the association with social measures was eliminated when relationship status was accounted for, as those with COPD were less frequently partnered. They more frequently endorsed depressive symptoms (32.0 vs. 18.9%, adjusted OR 1.9, 95% CI 1.4, 2.7). There was no noted difference in cognitive impairment between the two populations. CONCLUSIONS: Geriatric conditions are common among community-dwelling older adults with self-reported COPD. A "beyond the lung" approach to COPD care should center on active management of geriatric conditions, potentially leading to improved COPD management, and quality of life.

Exploring Shared Effects of Multisensory Impairment, Physical Dysfunction, and Cognitive Impairment on Physical Activity: An Observational Study in a National Sample.

Multisensory, physical, and cognitive dysfunction share age-related physiologic disturbances and may have common health effects. We determined whether the effect of multisensory impairment on physical activity (PA) is explained by physical (timed up and go) or cognitive (Short Portable Mental Status Questionnaire) dysfunction. A National Social Life, Health, and Aging Project participant subset (n = 507) underwent objective sensory testing in 2005-2006 and wrist accelerometry in 2010-2011. We related multisensory impairment to PA using multivariate mixed-effects linear regression and compared the effect magnitude after adjusting for physical then cognitive dysfunction. Worse multisensory impairment predicted lower PA across three scales (Global Sensory Impairment: ß = -0.04, 95% confidence interval [-0.07, -0.02]; Total Sensory Burden: ß = -0.01, 95% confidence interval [-0.03, -0.003]; and Number of Impaired Senses: ß = -0.02, 95% confidence interval [-0.04, -0.004]). Effects were similar after accounting for physical and cognitive dysfunction. Findings suggest that sensory, physical, and cognitive dysfunction have unique mechanisms underlying their PA effects.

Olfaction Is Associated With Sexual Motivation and Satisfaction in Older Men and Women.

BACKGROUND: Sensory function declines with age and may impact sexual function in older adults. Indeed, the sense of smell plays a uniquely strong role in sexual motivation. Therefore, olfactory dysfunction in older adults may be intimately linked to changes in sexual desire and satisfaction. AIM: To test whether impaired olfactory function is associated with decreased sexual activity and motivation in older adults. METHODS: Cross-sectional analysis of a nationally representative sample of community-dwelling older U.S. adults from the National Social Life, Health, and Aging Project. OUTCOMES: 2 modalities of olfactory function were measured (sensitivity to n-butanol and odor identification) via validated methods (Sniffin' Sticks). Respondents answered survey questions about frequency of sexual thoughts (motivation) and sexual activity, and satisfaction with their most recent sexual relationship. A wide range of demographic, health, and social information were also collected. RESULTS: Decreased olfactory function in older U.S. adults was associated with decreased sexual motivation (odds ratio 0.93, P = .03) and less emotional satisfaction with sex (odds ratio 0.89, P = .04), but not decreased frequency of sexual activity or physical pleasure, in analyses that were adjusted for age, gender, race, education, cognition, comorbidities, and depression. CLINICAL IMPLICATIONS: Olfactory dysfunction may affect sexuality in older adults. Potentially treatable causes of sensory loss should be addressed by clinicians to improve quality of life. STRENGTHS & LIMITATIONS: These results rely on validated olfactory testing, detailed measures of sexual attitudes and behaviors, and extensive demographic, health, and social history in a nationally representative sample of older U.S. adults. Owing to the cross-sectional nature of these analyses, we cannot determine causality. CONCLUSIONS: Olfactory dysfunction in older U.S. adults is associated with decreased sexual motivation and emotional satisfaction, potentially due to evolutionarily-conserved neurological links between olfaction and sexuality. Siegel JK, Kung SY, Wroblewski KE, et al. Olfaction Is Associated With Sexual Motivation and Satisfaction in Older Men and Women. J Sex Med 2021;18:295-302.

Sleep-Disordered Breathing Is Associated With Impaired Odor Identification in Older U.S. Adults.

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.

Olfactory Dysfunction Predicts the Development of Depression in Older US Adults.

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.

IL-1Rahigh-IL-4low-IL-13low: A Novel Plasma Cytokine Signature Associated with Olfactory Dysfunction in Older US Adults.

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.

Odor Sensitivity Versus Odor Identification in Older US Adults: Associations With Cognition, Age, Gender, and Race.

The ability to identify odors predicts morbidity, mortality, and quality of life. It varies by age, gender, and race and is used in the vast majority of survey and clinical literature. However, odor identification relies heavily on cognition. Other facets of olfaction, such as odor sensitivity, have a smaller cognitive component. Whether odor sensitivity also varies by these factors has not been definitively answered. We analyzed data from the National Social Life, Health, and Aging Project, a nationally representative study of older US adults (n = 2081). Odor identification was measured using 5 validated odors presented with Sniffin' Stick pens as was odor sensitivity in a 6-dilution n-butanol constant stimuli detection test. Multivariate ordinal logistic regression modeled relationships between olfaction and age, gender, race, cognition, education, socioeconomic status, social network characteristics, and physical and mental health. Odor sensitivity was worse in older adults (P < 0.01), without gender (P = 0.56) or race (P = 0.79) differences. Odor identification was also worse in older adults, particularly men (both P ≤ 0.01), without differences by race. Decreased cognitive function was associated with worse odor identification (P ≤ 0.01) but this relationship was weaker for odor sensitivity (P = 0.02) in analyses that adjusted for other covariates. Odor sensitivity was less strongly correlated with cognitive ability than odor identification, confirming that it may be a more specific measure of peripheral olfactory processing. Investigators interested in associations between olfaction and health should consider both odor sensitivity and identification when attempting to understand underlying neurosensory mechanisms.

Olfactory dysfunction persists after smoking cessation and signals increased cardiovascular risk.

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.

Psychosocial Stress Exposure Disrupts Mammary Gland Development.

Exposure to psychosocial stressors and ensuing stress physiology have been associated with spontaneous invasive mammary tumors in the Sprague-Dawley rat model of human breast cancer. Mammary gland (MG) development is a time when physiologic and environmental exposures influence breast cancer risk. However, the effect of psychosocial stress exposure on MG development remains unknown. Here, in the first comprehensive longitudinal study of MG development in nulliparous female rats (from puberty through young adulthood; 8-25 wks of age), we quantify the spatial gradient of differentiation within the MG of socially stressed (isolated) and control (grouped) rats. We then demonstrate that social isolation increased stress reactivity to everyday stressors, resulting in downregulation of glucocorticoid receptor (GR) expression in the MG epithelium. Surprisingly, given that chemical carcinogens increase MG cancer risk by preventing normal terminal end bud (TEB) differentiation, chronic isolation stress did not alter TEBs. Instead, isolation blunted MG growth and alveolobular differentiation and reduced epithelial cell proliferation in these structures. Social isolation also enhanced corpora luteal progesterone at all ages but reduced estrogenization only in early adulthood, a pattern that precludes modulated ovarian function as a sufficient mechanism for the effects of isolation on MG development. This longitudinal study of natural variation provides an integrated view of MG development and the importance of increased GR activation in nulliparous ductal growth and alveolobular differentiation. Thus, social isolation and its physiological sequelae disrupt MG growth and differentiation and suggest a contribution of stress exposure during puberty and young adulthood to the previously observed increase in invasive MG cancer observed in chronically socially-isolated adult Sprague-Dawley rats.