David W. Kern

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.

Racial Disparities in Olfactory Loss Among Older Adults in the United States

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.

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.

Global Sensory Impairment in Older Adults in the United States

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.

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 &agr;=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.

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.

Field Survey Measures of Olfaction The Olfactory Function Field Exam (OFFE)

Population-based field research on human olfaction has been limited by a lack of feasible assessment tools. Previous olfactory survey research has measured only odor identification, with no research being done on odor detection (i.e., a person’s sensitivity to detect a particular odor). Laboratory studies suggest that deficits in both aspects of olfactory function may be related to physical health, mental health and cognition, social function, including overall quality of life, and even mortality. However, field studies are needed to validate and extend these findings in large representative samples. Here we describe the olfactory function field exam, an instrument that can be deployed in field environments by lay interviewers to evaluate both odor identification and odor detection rapidly, practically, and accurately. Use of this new survey tool in future field-based population health studies will elucidate the impact of olfactory function on a myriad of health and social conditions.

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 smells role in physical, social, and mental health with aging.

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 androstadienones 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.

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.