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.

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.

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.

Cognitive Function and its Risk Factors Among Older US Adults Living at Home.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) has not been administered to a representative national sample, precluding comparison of patient scores to the general population and for risk factor identification. METHODS: A validated survey-based adaptation of the MoCA (MoCA-SA) was administered to a probability sample of home-dwelling US adults aged 62 to 90, using the National Social Life, Health, and Aging Project (n=3129), yielding estimates of prevalence in the United States. The association between MoCA-SA scores and sociodemographic and health-related risk factors were determined. RESULTS: MoCA-SA scores decreased with age, and there were substantial differences among sex, education, and race/ethnicity groups. Poor physical health, functional status, and depression were also associated with lower cognitive performance; current health behaviors were not. Using the recommended MoCA cut-point score for Mild Cognitive Impairment (MoCA score <26; MoCA-SA score <17), 72% (95% confidence interval, 69% to 74%) of older US adults would be classified as having some degree of cognitive impairment. CONCLUSIONS: Our results provide an important national estimate for interpreting MoCA scores from individual patients, and establish wide variability in cognition among older home-dwelling US adults. Care should be taken in applying previously-established MoCA cut-points to the general population, especially when evaluating individuals from educationally and ethnically diverse groups.

Olfactory Dysfunction Predicts Subsequent Dementia in Older U.S. Adults.

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.

Global Sensory Impairment Predicts Morbidity and Mortality in Older U.S. Adults.

OBJECTIVES: To evaluate global sensory impairment (GSI, an integrated measure of sensory dysfunction) as a predictor of physical function, cognition, overall health, and mortality. DESIGN: Prospective study. SETTING: The National Social Life, Health, and Aging Project. PARTICIPANTS: A national probability sample of 3,005 home-dwelling older U.S. adults assessed at baseline (2005-06) and 5-year follow-up (2010-11). MEASUREMENTS: Gait speed, activity, disability, cognition, overall health, 5-year mortality. RESULTS: At baseline, older adults with worse GSI were slower (Timed Up and Go times: odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.17-1.50) and had more activity of daily living deficits (≥2: OR = 1.26, 95% CI = 1.10-1.46). Five years later, they were still slower (timed walk: OR = 1.22, 95% CI = 1.05-1.42), had more disabilities (≥2 instrumental activities of daily living; OR = 1.45, 95% CI = 1.23-1.70), were less active (daytime activity according to accelerometry: ß = -2.7, 95% CI = -5.2 to -0.2), had worse cognitive function (Montreal Cognitive Assessment; ß = -0.64, 95% CI = -0.84 to -0.44), more likely to have poorer overall health (OR = 1.16, 95% CI = 1.03-1.31) and lose weight (>10%: OR = 1.31, 95% CI = 1.04-1.64), and have died (OR = 1.45, 95% CI = 1.19-1.76). All analyses were adjusted for relevant confounders at baseline, including age, sex, race and ethnicity, education, smoking, problem drinking, body mass index, comorbidities, and cognitive function. CONCLUSION: GSI predicts impaired physical function, cognitive dysfunction, significant weight loss, and mortality 5 years later in older U.S. adults. Multisensory evaluation may identify vulnerable individuals, offering the opportunity for early intervention to mitigate adverse outcomes.

A human chemosignal modulates frontolimbic activity and connectivity in response to emotional stimuli.

Evidence suggests the putative human pheromone Δ4,16-androstadien-3-one (androstadienone), a natural component of human sweat, increases attention to emotional information when passively inhaled, even in minute amounts. However, the neural mechanisms underlying androstadienone's impact on the perception of emotional stimuli have not been clarified. To characterize how the compound modifies neural circuitry while attending to emotional information, 22 subjects (11 women) underwent two fMRI scanning sessions, one with an androstadienone solution and one with a carrier control solution alone on their upper lip. During each session, participants viewed blocks of emotionally positive, negative, or neutral images. The BOLD response to emotional images (relative to neutral images) was greater during exposure to androstadienone in right orbitofrontal and lateral prefrontal cortex, particularly during positive image blocks. Androstadienone did not impact the response to social images, compared to nonsocial images, and results were not related to participant sex or olfactory sensitivity. To examine how androstadienone influences effective connectivity of this network, a dynamic causal model was employed with primary visual cortex (V1), amygdala, prefrontal cortex, and orbitofrontal cortex on each side. These models indicated that emotional images increased the drive from V1 to the amygdala during the control session. With androstadienone present, this drive to amygdala was decreased specifically for positive images, which drove downstream increases in orbitofrontal and prefrontal activity. This evidence suggests that androstadienone may act as a chemical signal to increase attention to positively valenced information via modifications to amygdala connectivity.

Factors Associated with Inaccurate Self-Reporting of Olfactory Dysfunction in Older US Adults.

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.

Fine particulate matter exposure and olfactory dysfunction among urban-dwelling older US adults.

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 (PM2.5) 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 PM2.5 exposures averaged over 3-12 months in urban-dwelling respondents. The strongest effect was for 6 month average exposure (per 1-IQR increase in PM2.5: 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.

Nitrogen dioxide pollution exposure is associated with olfactory dysfunction in older U.S. adults.

BACKGROUND: Olfactory dysfunction has profound effects on quality of life, physical and social function, and mortality itself. Nitrogen dioxide (NO2 ) 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 NO2 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 NO2 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 NO2 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 NO2 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 NO2 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 NO2 exposure is associated with olfactory dysfunction in older U.S. adults. These results suggest an important role for NO2 exposure on olfactory dysfunction, and, potentially, nasal disease more broadly.

Global Sensory Impairment in Older Adults in the United States.

OBJECTIVES: To determine whether there may be a common mechanism resulting in global sensory impairment of the five classical senses (vision, smell, hearing, touch, and taste) in older adults. DESIGN: Representative, population-based study. SETTING: National Social Life, Health, and Aging Project. PARTICIPANTS: Community-dwelling U.S. adults aged 57 to 85. MEASUREMENTS: The frequency with which impairment co-occurred across the five senses was estimated as an integrated measure of sensory aging. It was hypothesized that multisensory deficits would be common and reflect global sensory impairment that would largely explain the effects of age, sex, and race on sensory dysfunction. RESULTS: Two-thirds of subjects had two or more sensory deficits, 27% had just one, and 6% had none. Seventy-four percent had impairment in taste, 70% in touch, 22% in smell, 20% in corrected vision, and 18% in corrected hearing. Older adults, men, African Americans, and Hispanics had greater multisensory impairment (all P < .01). Global sensory impairment largely accounted for the effects of age, sex, and race on the likelihood of impairment in each of the five senses. CONCLUSION: Multisensory impairment is prevalent in older U.S. adults. These data support the concept of a common process that underlies sensory aging across the five senses. Clinicians assessing individuals with a sensory deficit should consider further evaluation for additional co-occurring sensory deficits.

The Rate of Age-Related Olfactory Decline Among the General Population of Older U.S. Adults.

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.

Olfactory thresholds of the U.S. Population of home-dwelling older adults: development and validation of a short, reliable measure.

Current methods of olfactory sensitivity testing are logistically challenging and therefore infeasible for use in in-home surveys and other field settings. We developed a fast, easy and reliable method of assessing olfactory thresholds, and used it in the first study of olfactory sensitivity in a nationally representative sample of U.S. home-dwelling older adults. We validated our method via computer simulation together with a model estimated from 590 normosmics. Simulated subjects were assigned n-butanol thresholds drawn from the estimated normosmic distribution and based on these and the model, we simulated administration of both the staircase and constant stimuli methods. Our results replicate both the correlation between the two methods and their reliability as previously reported by studies using human subjects. Further simulations evaluated the reliability of different constant stimuli protocols, varying both the range of dilutions and number of stimuli (6-16). Six appropriately chosen dilutions were sufficient for good reliability (0.67) in normosmic subjects. Finally, we applied our method to design a 5-minute, in-home assessment of older adults (National Social Life, Health and Aging Project, or NSHAP), which had comparable reliability (0.56), despite many subjects having estimated thresholds above the strongest dilution. Thus, testing with a fast, 6-item constant stimuli protocol is informative, and permits olfactory testing in previously inaccessible research settings.

Evaluation of a Brief Survey Instrument for Assessing Subtle Differences in Cognitive Function Among Older Adults.

Most measures of cognitive function used in large-scale surveys of older adults have limited ability to detect subtle differences across cognitive domains, and standard clinical instruments are impractical to administer in general surveys. The Montreal Cognitive Assessment (MoCA) can address this need, but has limitations in a survey context. Therefore, we developed a survey adaptation of the MoCA, called the MoCA-SA, and describe its psychometric properties in a large national survey. Using a pretest sample of older adults (n=120), we reduced MoCA administration time by 26%, developed a model to accurately estimate full MoCA scores from the MoCA-SA, and tested the model in an independent clinical sample (n=93). The validated 18-item MoCA-SA was then administered to community-dwelling adults aged 62 to 91 as part of the National Social life Health and Aging Project Wave 2 sample (n=3196). In National Social life Health and Aging Project Wave 2, the MoCA-SA had good internal reliability (Cronbach α=0.76). Using item-response models, survey-adapted items captured a broad range of cognitive abilities and functioned similarly across sex, education, and ethnic groups. Results demonstrate that the MoCA-SA can be administered reliably in a survey setting while preserving sensitivity to a broad range of cognitive abilities and similar performance across demographic subgroups.

Olfactory function in Wave 2 of the National Social Life, Health, and Aging Project.

OBJECTIVE: To investigate the sense of smell, including sensitivity and odor identification, and characterize the U.S. national prevalence of olfactory dysfunction in older adults, thereby facilitating further investigation of the substantial risks for older adults associated with this basic sensory ability. METHOD: The sense of smell was evaluated using the Olfactory Function Field Exam (OFFE), a measure designed specifically for field research, which assesses 3 components of olfaction: sensitivity to n-butanol (a standard testing odorant) and androstadienone (AND, a key social odor produced by humans), as well as the ability to identify odors. Respondents were randomly selected from the National Social Life, Health, and Aging Project Wave 2 sample to receive the OFFE (n = 2,304), and 2,212 consented to participate. RESULTS: In the U.S. population aged 62-90, n-butanol detection ability was significantly worse at older ages (ordinal logistic regression, p < .001); however, there was no difference in detection ability between genders (p = .60). AND detection ability was also significantly worse at older ages (p = .003), but in contrast to n-butanol, women outperformed men (p = .001). As expected, odor identification ability was worse in older people than in younger (p < .001), and women were more accurate than men (p = .001). DISCUSSION: We report for the first time 3 facets of olfactory function and its association with age and gender in a representative sample of U.S. older adults. Future analyses of these data are needed to elucidate the sense of smell's role in physical, social, and mental health with aging.

Sensory function: insights from Wave 2 of the National Social Life, Health, and Aging Project.

OBJECTIVES: Sensory function, a critical component of quality of life, generally declines with age and influences health, physical activity, and social function. Sensory measures collected in Wave 2 of the National Social Life, Health, and Aging Project (NSHAP) survey focused on the personal impact of sensory function in the home environment and included: subjective assessment of vision, hearing, and touch, information on relevant home conditions and social sequelae as well as an improved objective assessment of odor detection. METHOD: Summary data were generated for each sensory category, stratified by age (62-90 years of age) and gender, with a focus on function in the home setting and the social consequences of sensory decrements in each modality. RESULTS: Among both men and women, older age was associated with self-reported impairment of vision, hearing, and pleasantness of light touch. Compared with women, men reported significantly worse hearing and found light touch less appealing. There were no gender differences for vision. Overall, hearing loss seemed to have a greater impact on social function than did visual impairment. DISCUSSION: Sensory function declines across age groups, with notable gender differences for hearing and light touch. Further analysis of sensory measures from NSHAP Wave 2 may provide important information on how sensory declines are related to health, social function, quality of life, morbidity, and mortality in this nationally representative sample of older adults.

Measuring cognition: the Chicago Cognitive Function Measure in the National Social Life, Health and Aging Project, Wave 2.

OBJECTIVES: To describe the development of a multidimensional test of cognition for the National Social life, Health and Aging Project (NSHAP), the Chicago Cognitive Function Measure (CCFM). METHOD: CCFM development included 3 steps: (a) A pilot test of the Montreal Cognitive Assessment (MoCA) to create a standard protocol, choose specific items, reorder items, and improve clarity; (b) integration into a CAPI-based format; and (c) evaluation of the performance of the CCFM in the field. The CCFM was subsequently incorporated into NSHAP, Wave 2 (n = 3,377). RESULTS: The pre-test (n = 120) mean age was 71.35 (SD 8.40); 53% were female, 69% white, and 70% with college or greater education. The MoCA took an average of 15.6min; the time for the CCFM was 12.0 min. CCFM scores (0-20) can be used as a continuous outcome or to adjust for cognition in a multivariable analysis. CCFM scores were highly correlated with MoCA scores (r = .973). Modeling projects MoCA scores from CCFM scores using the equation: MoCA = (1.14 × CCFM) + 6.83. In Wave 2, the overall weighted mean CCFM score was 13.9 (SE 0.13). DISCUSSION: A survey-based adaptation of the MoCA was successfully integrated into a nationally representative sample of older adults, NSHAP Wave 2.

Survey field methods for expanded biospecimen and biomeasure collection in NSHAP Wave 2.

OBJECTIVES: The National Social Life, Health, and Aging Project is a nationally representative, longitudinal survey of older adults. A main component is the collection of biomeasures to objectively assess physiological status relevant to psychosocial variables, aging conditions, and disease. Wave 2 added novel biomeasures, refined those collected in Wave 1, and provides a reference for the collection protocols and strategy common to the biomeasures. The effects of aging, gender, and their interaction are presented in the specific biomeasure papers included in this Special Issue. METHOD: A transdisciplinary working group expanded the biomeasures collected to include physiological, genetic, anthropometric, functional, neuropsychological, and sensory measures, yielding 37 more than in Wave 1. All were designed for collection in respondents' homes by nonmedically trained field interviewers. RESULTS: Both repeated and novel biomeasures were successful. Those in Wave 1 were refined to improve quality, and ensure consistency for longitudinal analysis. Four new biospecimens yielded 27 novel measures. During the interview, 19 biomeasures were recorded covering anthropometric, functional, neuropsychological, and sensory measures and actigraphy provided data on activity and sleep. DISCUSSION: Improved field methods included in-home collection, temperature control, establishment of a central survey biomeasure laboratory, and shipping, all of which were crucial for successful collection by the field interviewers and accurate laboratory assay of the biomeasures (92.1% average co-operation rate and 97.3% average assay success rate). Developed for home interviews, these biomeasures are readily applicable to other surveys.

Olfactory dysfunction predicts 5-year mortality in older adults.

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.

Quantitative Validation of the n-Butanol Sniffin' Sticks Threshold Pens.

Odorant pens are used by medical practitioners and researchers to assess olfactory dysfunction. Despite their routine use, there are currently no data on the gas-phase odorant concentrations released from the pen tips or whether these concentrations scale linearly with the aqueous-phase concentrations inside the pens. The commercially available Sniffin' Sticks odor threshold test containing n-butanol was chosen for evaluation. The gas-phase concentration of n-butanol at the tip of each pen was measured directly in a new set of pens via proton-transfer-reaction mass spectrometry (PTR-MS). Measurements were additionally made on the same pens after 6 months and two older pen sets, namely a 3-year-old (used) and 4-year-old (new) set. Furthermore, application-related tests were made to determine the performance of the pens during routine use and under stress. These data demonstrate that the gas-phase n-butanol concentrations of the threshold pens are linear over the entire set, both for brand-new pens and 6 months later; this reflects the expected performance that was previously only assumed. Furthermore, the application-simulation tests demonstrated a good performance of the pens when used according to their intended protocol. Measurements of the older pen sets suggest that storage conditions are more critical than usage for pen stability. The present findings confirm that the n-butanol odorant pens are an appropriate tool for threshold testing, provided they are stored and handled correctly. Figureᅟ