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RATIONALE: Studies have suggested heightened anxiety among adults with asthma; the mechanism of this association is not known. OBJECTIVES: To determine the association between post-traumatic stress disorder (PTSD) symptoms and asthma among adults, and to examine if this association is due to confounding by environmental and genetic factors. METHODS: Data were obtained from twins in the Vietnam Era Twin Registry, which includes male veteran twin pairs born between 1939 and 1956 who served during the Vietnam era (1965-1975). Measurements included a symptom scale for PTSD, history of a doctor diagnosis of asthma, and sociodemographic and health confounding factors. Co-twin control analytic methods used mixed-effects logistic regression to account for the paired structure of the twin data and to examine the association between PTSD symptoms and asthma in all twins. Separate analyses were conducted within twin pairs and according to zygosity. MEASUREMENTS AND MAIN RESULTS: PTSD symptoms were associated with a significantly increased likelihood of asthma (P(trend) < 0.001) even after adjustment for confounding factors. Among all twins, those in the highest quartile of PTSD symptoms were 2.3 times as likely (95% confidence interval, 1.4-3.7) to have asthma compared with those in the lowest quartile. These findings persist when examined within twin pairs and when stratified by zygosity. CONCLUSIONS: Symptoms of PTSD were associated with an elevated prevalence of asthma. Even after careful adjustment for familial/genetic factors and other potential confounding factors, an association between PTSD symptoms and asthma remains. Efforts to understand this comorbidity may be useful in identifying modifiable environmental risk factors contributing to this pattern and therefore in developing more effective prevention and intervention strategies. [ABSTRACT FROM AUTHOR]

This study's aim was to identify risk factors associated with sensorineural and neurocognitive function (brain aging) in older adults. In N  = 1,478 Epidemiology of Hearing Loss Study participants (aged 64-100 years, 59% women), we conducted sensorineural and cognitive tests, which were combined into a summary measure using Principal Component Analysis (PCA). Participants with a PCA score <-1 standard deviation (SD) were considered to have brain aging. Incident brain aging was defined as PCA score <-1 SD at 5-year follow-up among participants who had a PCA score ≥-1 SD at baseline. Logistic regression and Poisson models were used to estimate associations between baseline risk factors of lifestyle, vascular and metabolic health, and inflammation and prevalent or incident brain aging, respectively. In an age-sex adjusted multivariable model, not consuming alcohol (odds ratio(OR) = 1.77, 95% confidence Interval (CI) = 1.18,2.66), higher interleukin-6 levels (OR = 1.30, 95% CI = 1.03,1.64), and depressive symptoms (OR = 2.44, 95% CI = 1.63,3.67) were associated with a higher odds of having brain aging, while higher education had protective effects (OR = 0.55, 95% CI = 0.33,0.94). A history of stroke, arterial stiffness, and obesity were associated with an increased risk of developing brain aging during the five years of follow-up. Lifestyle, vascular, metabolic and inflammatory factors were associated with brain aging in older adults, which adds to the evidence of shared pathways for sensorineural and neurocognitive declines in aging. Targeting these shared central processing etiological factors with interventions may lead to retention of better neurological function, benefiting multiple systems, i.e., hearing, smell, and cognition, ultimately helping older adults retain independence and higher quality of life longer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Merten, Fischer, Pinto, Chappell and Schubert.)

ObjectivesDetermine associations of hearing loss (HL) and hearing aid (HA) use with cognition, health-related quality of life (HRQoL), and depressive symptoms. Methods: Participants were from the Epidemiology of Hearing Loss Study or Beaver Dam Offspring Study. HL was defined as pure-tone average (.5-4.0 kHz) > 25 dB. A principal component analysis of 5 cognitive tasks measured cognition. The SF-12 measured mental and physical HRQoL. The Centers for Epidemiological Studies Depression Scale measured depressive symptoms (score ≥ 16). Regression models returned beta (B) coefficients or odds ratios (OR) with 95% confidence intervals. Results: This study included 3574 participants. HL (vs. none) was associated with poorer cognition (B-.12 [-.18, -.06]), mental (B-.99 [-1.65, -.33]) and physical (B-.76 [-1.50, -.03]) HRQoL, and increased odds of depressive symptoms (OR 1.49 [1.16, 1.91]). HA users had better cognition than non-users. Discussion: HL likely impacts cognition and well-being. HA use may have cognitive benefits.

Background: Age-related declines in cognitive function may begin in midlife., Purpose: To determine whether blood-based biomarkers of inflammation, metabolic dysregulation and neurotoxins are associated with risk of cognitive decline and impairment., Methods: Baseline blood samples from the longitudinal Beaver Dam Offspring Study (2005-2008) were assayed for markers of inflammation, metabolic dysregulation, and environmental neurotoxins. Cognitive function was measured at baseline, 5-year (2010-2013) and 10-year (2015-2017) examinations. Participants without cognitive impairment at baseline and with cognitive data from at least one follow-up were included. Cox proportional hazards models were used to evaluate associations between baseline blood biomarkers and the 10-year cumulative incidence of cognitive impairment. Poisson models were used to estimate the relative risk (RR) of 5-year decline in cognitive function by baseline blood biomarkers. Models were adjusted for age, sex, education, and cardiovascular related risk factors., Results: Participants (N = 2421) were a mean age of 49 years and 55% were women. Soluble vascular cell adhesion molecule-1 (sVCAM-1 Tertile(T)3 vs T1-2 hazard ratio (HR) = 1.72, 95% confidence interval (CI) = 1.05,2.82) and hemoglobin A1C (HR = 1.75, 95% CI = 1.18,2.59, per 1% in women) were associated with the 10-year cumulative incidence of cognitive impairment. sVCAM-1 (RR T3 vs T1-2  = 1.45, 95% CI = 1.06,1.99) and white blood cell count (RR = 1.10, 95% CI = 1.02,1.19, per 10 3 /μL) were associated with 5-year cognitive decline., Conclusions: Biomarkers related to inflammation and metabolic dysregulation were associated with an increased risk of developing cognitive decline and impairment. These results extend previous research in cognitive aging to early markers of cognitive decline in midlife, a time when intervention methods may be more efficacious., (© 2022. Fondazione Società Italiana di Neurologia.)

Objectives: Psychological well-being (PWB) may be a potential modifiable risk factor of age-related diseases. We aimed to determine associations of PWB with sensorineural and cognitive function and neuronal health in middle-aged adults., Methods: This study included 2039 Beaver Dam Offspring Study participants. We assessed PWB, hearing, visual acuity, contrast sensitivity impairment, olfactory impairment, cognition, and retinal (macular ganglion cell inner-plexiform layer, mGCIPL) thickness. Age-sex-education-adjusted multivariable linear, logistic regression, and generalized estimating equation models were used and then further adjusted for health-related confounders., Results: Individuals with higher PWB had better hearing functions, visual acuity, and thicker mGCIPL and reduced odds for hearing, contrast sensitivity and olfactory impairment in age-sex-education-adjusted models. Effects on mGCIPL and visual and olfactory measures decreased with adjustment. Higher PWB was associated with better cognition, better combined sensorineural-cognitive function, and decreased cognitive impairment., Discussion: Psychological well-being was associated with sensorineural-cognitive health indicating a potential of PWB interventions for healthy aging.

Purpose: Hearing loss (HL) is common among middle-age and older adults, but hearing aid adoption is low. The purpose of this study was to measure the 10-year incidence of hearing aid adoption in a sample of primarily middle-age adults with high-frequency HL and identify factors associated with hearing aid adoption., Method: This study included 579 adults (ages 34-80 years) with high-frequency pure-tone average > 25 dB HL (3-8 kHz) enrolled in the Beaver Dam Offspring Study. Hearing aid adoption was measured at 5- and 10-year follow-up examinations. Cox discrete-time proportional hazards models were used to evaluate factors associated with hearing aid adoption (presented as hazards ratios [HRs] and 95% confidence intervals [95% CI])., Results: The 10-year cumulative incidence of hearing aid adoption was 14 per 1,000 person years. Factors significantly associated with adoption in a multivariable model were higher education (vs. 16+ years; 0-12: HR: 0.36, 95% CI [0.19, 0.69]; 13-15: HR: 0.52, 95% CI [0.27, 0.98]), worse high-frequency pure-tone average (per +1 dB; HR: 1.04, 95% CI [1.02, 1.06]), self-reported hearing handicap (screening versions of the Hearing Handicap Inventory score > 8; HR: 1.85, 95% CI [1.02, 3.38]), answering yes to "Do friends and relatives think you have a hearing problem?" (HR: 3.18, 95% CI [1.60, 6.33]) and using closed captions (HR: 2.86, 95% CI [1.08, 7.57]). Effects of age and sex were not significant., Conclusions: Hearing aid adoption rates were low. Hearing sensitivity, socioeconomic status, and measures of the impact of HL on daily life were associated with adoption. Provider awareness of associated factors can contribute to timely and appropriate intervention.

Objective: The purpose of this study was to (i) develop a model that predicts hearing aid (HA) use and (ii) determine if model fit is improved by adding factors not typically collected in audiological evaluations., Design: Two models were created and evaluated. The "clinical" model used factors typically collected during audiologic clinical evaluations. The "expanded" model considered additional clinical, health and lifestyle factors to determine if the model fit could be improved (compared to clinical model). Models were created with least absolute shrinkage and selection operator (LASSO) logistic regression with 10-fold cross validation. Predictive ability was evaluated via receiver operating characteristic curves and concordance statistics (c-statistics)., Study Sample: This study included 275 participants from the Beaver Dam Offspring Study, a prospective longitudinal cohort study of aging, with a treatable level of hearing loss and no HA use at baseline., Results: The clinical and expanded models report predictors important for HA use. The c-statistics of the clinical (0.80) and expanded (0.79) models were not significantly different ( p  = 0.41)., Conclusions: Similar predictive abilities of models suggest audiological evaluations perform well in predicting HA use.

Purpose The aim of this study was to determine the long-term associations of musical training with speech perception in adverse conditions and cognition in a longitudinal cohort study of middle-age to older adults. Method This study is based on Epidemiology of Hearing Loss Study participants. We asked participants at baseline (1993-1995) about their musical training. Speech perception (word recognition in competing message; Northwestern University Auditory Test Number 6), cognitive function (cognitive test battery), and impairment (self-report or surrogate report of Alzheimer's disease or dementia, and/or a Mini-Mental State Examination score ≤ 24) were assessed up to 5 times over the 20-year follow-up. We included 2,938 Epidemiology of Hearing Loss Study participants who had musical training data and at least one follow-up of speech perception and/or cognitive assessment. We used linear mixed-effects models to determine associations between musicianship and decline in speech perception and cognitive function over time and Cox regression models to evaluate associations of musical training with 20-year cumulative incidence of speech perception and cognitive impairment. Models were adjusted for age, sex, and occupation and repeated with additional adjustment for health-related confounders and education. Results Musicians showed less speech perception decline over time with stronger effects in women (0.16% difference, 95% confidence interval [CI] [0.05, 0.26]). Among men, musicians had, on average, better speech perception than nonmusicians (3.41% difference, 95% CI [0.62, 6.20]) and were less likely to develop a cognitive impairment than nonmusicians (hazard ratio = 0.58, 95% CI [0.37, 0.91]). Conclusions Musicians showed an advantage in speech perception abilities and cognition later in life and less decline over time with different magnitudes of effect sizes in men and women. Associations remained with further adjustment, indicating that some degree of the advantage of musical training is independent of socioeconomic or health differences. If confirmed, these findings could have implications for developing speech perception intervention and prevention strategies. Supplemental Material https://doi.org/10.23641/asha.14825454.

Purpose: To determine if incidence of contrast sensitivity (CS) impairment differs by generation and identify factors to explain these differences., Methods: The Beaver Dam Eye Study (BDES) and Beaver Dam Offspring Study (BOSS) are cohort studies of aging adults in Beaver Dam, Wisconsin. Baseline examinations occurred from 1993 to 1995 (BDES) and 2005-2008 (BOSS). Follow-up examinations occurred in five-year intervals. CS testing was conducted with Pelli-Robson letter sensitivity charts; Incident impairment was a log CS score <1.55 in either eye at follow-up. Associations of incidence with generation were investigated using estimated hazard ratios (HR) with 95% confidence intervals (CI)., Results: Participants (N = 3185) had a mean age of 51.9 years at baseline (standard deviation = 9.9) and 51.9% were female. Ten-year cumulative incidence of CS impairment was 40.1%, was higher among women (41.7%) than men (38.8%), and increased by age group. The risk of incident CS impairment decreased by 39% per generation. In multivariable models, the Baby Boom Generation (HR = 0.42, 95%CI = 0.31, 0.58) and Generation X (HR = 0.56, 95%CI = 0.34, 0.91) had a significantly decreased risk of CS impairment compared to the Greatest Generation. Results were similar in sensitivity analyses excluding those with cataract, age-related macular degeneration, or visual acuity impairment., Conclusion: The risk of incident CS impairment decreased by birth cohort, with the greatest reduction in the Baby Boom Generation. The difference in risk suggests that there are unknown modifiable risk factors that may help to further explain the etiology of CS impairment and provide potential pathways for prevention in the future.

Significance: The macular ganglion cell-inner plexiform layer (mGCIPL) may serve as a quick and easily obtained measure of generalized neurodegeneration. Investigating factors associated with this thickness could help to understand neurodegenerative processes., Purpose: This study aimed to characterize and identify associated factors of the mGCIPL thickness in a Beaver Dam Offspring Study cohort of middle-aged U.S. adults., Methods: Baseline examinations occurred from 2005 to 2008, with follow-up examinations every 5 years. Included participants had baseline data and measured mGCIPL at 10-year follow-up (N = 1848). The mGCIPL was measured using the Cirrus 5000 HD-OCT Macular Cube Scan. Associations between mean mGCIPL thickness and thin mGCIPL, defined as 1 standard deviation (SD) below the population mean, and baseline risk factors were investigated using generalized estimating equations., Results: Participants (mean [SD] baseline age, 48.9 [9.3] years; 54.4% women) had mean (SD) mGCIPL thicknesses of 78.4 (8.1) μm in the right eye and 78.1 (8.5) μm in the left (correlation coefficient = 0.76). In multivariable models, age (-1.07 μm per 5 years; 95% confidence interval [CI], -1.28 to -0.86 μm), high alcohol consumption (-1.44 μm; 95% CI, -2.72 to -0.16 μm), higher interleukin 6 levels (50% increase in level: -0.23 μm; 95% CI, -0.45 to 0.00 μm), myopia (-2.55 μm; 95% CI, -3.17 to -1.94 μm), and glaucoma (-1.74 μm; 95% CI, -2.77 to -0.70 μm) were associated with thinner mGCIPL. Age (per 5 years: odds ratio [OR], 1.38; 95% CI, 1.24 to 1.53), diabetes (OR, 1.89, 95% CI, 1.09 to 3.27), myopia (OR, 2.11; 95% CI, 1.63 to 2.73), and increasing and long-term high C-reactive protein (ORs, 1.46 [95% CI, 1.01 to 2.11] and 1.74 [95% CI, 1.14 to 2.65], respectively) were associated with increased odds of thin mGCIPL., Conclusions: Factors associated cross-sectionally with mGCIPL thickness, older age, high alcohol consumption, inflammation, diabetes, myopia, and glaucoma may be important to neural retina structure and health and neuronal health system-wide., Competing Interests: Conflict of Interest Disclosure: The authors have no conflicts of interest to declare. This work was supported by Award Number R01AG021917 from the National Institute on Aging (KJC) and an unrestricted grant from Research to Prevent Blindness to the Department of Ophthalmology and Visual Science at the University of Wisconsin School of Medicine and Public Health. The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis, as well as the decision to submit for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Aging or Research to Prevent Blindness., (Copyright © 2021 American Academy of Optometry.)

Importance: Age-adjusted prevalence of hearing impairment (HI) decreased across generations in the 20th century, suggesting that HI is partially preventable. It is not known whether HI incidence differs by generation., Objectives: To examine whether HI incidence and change in pure-tone average (PTA) differ by generation and identify factors underlying these differences., Design, Setting, and Participants: This cohort study used data from the Epidemiology of Hearing Loss Study (EHLS) and Beaver Dam Offspring Study (BOSS), a pair of studies of adults in Beaver Dam, Wisconsin. Baseline examinations occurred from 1993 to 1995 in the EHLS and 2005 to 2008 in BOSS, with two 5-year follow-up examinations in each cohort. This longitudinal cohort study assessed 3651 participants without HI at baseline who had follow-up data., Main Outcomes and Measures: The primary outcome was incident HI measured by pure-tone audiometry, defined as PTA greater than 25-dB hearing level (dB HL) in either ear. Associations of 5-year incidence were estimated by relative risks (RRs) and 10-year cumulative incidence with generation, as categorized by commonly used sociodemographic descriptors of year of birth, by hazard ratios (HRs). The 10-year change in PTA was investigated using a generation × time interaction term in generalized estimating equation models., Results: Among the 3651 participants (mean [SD] age at baseline 53.1 [10.6] years; 2255 [61.8%] female; and 3567 [97.7%] non-Hispanic White), the 5-year HI incidence was 14.1% (95% CI, 13.0%-15.3%) and the 10-year cumulative incidence was 26.0% (95% CI, 24.6%-27.6%). The incidence increased with age. The risk of 5-year incident HI decreased by generation (RR, 0.80; 95% CI, 0.66-0.97) when adjusting for multiple covariates. The decreased risk was similar in the 10-year period (HR, 0.86; 95% CI, 0.73-1.01). The PTA change rate (per 5 years of follow-up) decreased by generation, with the Greatest Generation (born 1901-1924) experiencing the highest rate (7.03 dB HL). The rates were all significantly lower for the other generations (Silent Generation [born 1925-1945], 3.30 dB HL; Baby Boom Generation [born 1946-1964], 3.36 dB HL; and Generation X [born 1965-1984], 2.33 dB HL)., Conclusions and Relevance: This study suggests that the risk of HI and rate of PTA change is lower for the Silent Generation and Baby Boom Generation compared with the Greatest Generation. Part of this lower risk is likely associated with changes in modifiable factors. A potential continued benefit may exist for Generation X. Combined with the reduced risk of HI for the Silent Generation and Baby Boom Generation, this finding implies that the future HI burden may be lower than current estimates suggest.

Purpose The dichotic digits test (DDT) is commonly administered in clinical and research settings, but it is not well understood how performance changes in aging. The purpose of this study is to determine the 5-year change on the free recall task and right ear advantage (REA) in a population-based cohort and factors associated with change. Method Participants in the population-based Epidemiology of Hearing Loss Study, who completed the DDT during the fourth (2009-2010) and fifth (2013-2016) examination periods were included ( n = 865, M age = 72.8 years at baseline). Free recall DDT was administered using 25 sets of triple-digit pairs presented at 70 dB HL. The REA was calculated by subtracting the score in the left ear from the score in the right ear. Results In 5 years, most participants (62.4%) declined on free recall performance (mean decline = 3.0% [4.5 digits], p < .01). In age-sex-adjusted models, higher baseline scores, hearing impairment, and lower education were significantly associated with increased risk of decline. An REA at baseline (76.8%) and follow-up (77.9%) was common. Half of participants (50.6%) had a 5-year REA widening ( M = 1.9% [1.4 digits], p = .01). Older age, but not hearing impairment, was associated with increased risk of REA widening. Conclusions The 5-year decline on free recall recognition performance was not associated with age but was associated with hearing impairment, whereas the 5-year widening of REA was associated with age but not hearing impairment. These results indicate that the REA may be a more sensitive measure of aging of the central auditory system than free recall performance.

Background: Low central venous pressure (LCVP) anesthesia reduces blood loss during hepatic resection and historically has required a central venous catheter (CVC) for intra-operative monitoring. The aim of this study was to assess the effect of an evolution of practice to CVP monitoring without CVC on the perioperative outcomes after liver resection., Methods: A retrospective study of partial hepatectomy patients from 2007 to 2016 who were over 18 years of age was performed., Results: Of 3903 patients having partial hepatectomy, 2445 (62%) met inclusion criteria, and 404 (16%) had a CVC. Overall morbidity (33% non-CVC vs 38% CVC P = 0.076), major morbidity (16% vs 20% P = 0.067), and infective complications (superficial wound infection) 3% vs 4% P = 0.429; deep wound infection (5% vs 6% P = 0.720) did not differ between the two groups. In multivariate analysis, superficial wound infection, deep wound infection, and major complications were not associated with the presence of a CVC. All-cause mortality at 90 days was associated with CVC presence (OR 3.45, CI 1.74-6.85, P = 0.001) and age (OR 1.05, CI 1.02-1.08, P < 0.001)., Conclusion: Since the adoption of non-invasive CVP monitoring, there has been no increase in adverse peri-operative outcomes., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Neurodegenerative diseases are public health challenges in aging populations. Early identification of people at risk for neurodegeneration might improve targeted treatment. Noninvasive, inexpensive screening tools are lacking but are of great potential. Optical coherence tomography (OCT) measures the thickness of nerve cell layers in the retina, which is an anatomical extension of the brain and might be indicative of common underlying neurodegeneration. We aimed to determine the association of macular ganglion cell-inner plexiform layer (mGCIPL) thickness with cognitive and sensorineural function in midlife., Method: This cross-sectional study included 1,880 Beaver Dam Offspring Study participants (aged 27-93 years, mean 58) who participated in the 10-year follow-up examination. We assessed cognitive function and impairment, hearing sensitivity thresholds and impairment, central auditory processing, visual impairment, and olfactory impairment. We measured mGCIPL using the Cirrus 5000 HD-OCT Macular Cube Scan. Multivariable linear and logistic regression models adjusted for potential confounders were used to determine associations between mGCIPL thickness and cognitive and sensorineural functions, as well as for comparing participants with a thin mGCIPL (1 SD below average) to the remainder in those functions., Results: Thinner mGCIPL was associated with worse cognitive function, worse central auditory function, and visual impairment. We found an association of mGCIPL thickness with hearing sensitivity in women only and no association with impairment in hearing, olfaction, and cognition. Results on the thin group comparisons were consistent., Conclusions: mGCIPL thickness is associated with cognitive and sensorineural function and has the potential as a marker for neurodegeneration in middle-aged adults., (© 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.)

Objectives/hypothesis: To determine the 10-year incidence of hearing impairment (HI) and associated risk factors in the Beaver Dam Offspring Study (BOSS; 2004-present), a large middle-aged cohort followed for 10 years., Study Design: Prospective cohort study., Methods: Hearing thresholds were measured at baseline (2005-2008) and 5- (2010-2013) and 10-year (2015-2017) follow-up examinations. HI was defined as a pure-tone average >25 dB HL in either ear. BOSS participants free of HI at baseline with at least one follow-up examination (N = 2,065) were included. Potential risk factors evaluated included cardiovascular measures, health history, lifestyle factors, inflammatory markers, vitamins D and B12, lead, and cadmium., Results: Participants were 21 to 79 years (mean age = 47.9 years) at baseline. The 10-year cumulative HI incidence was 17.4% (95% confidence interval [CI]: 15.7-19.2) and was twice as likely in men (24.4%, 95% CI: 21.5-27.7) than in women (12.2%, 95% CI: 10.3-14.3). In a multivariable adjusted model, age (hazard ratio [HR] = 1.48, 95% CI: 1.38-1.59, per 5 years), male sex (HR = 2.47, 95% CI: 1.91-3.18), less than a college education (HR = 1.35, 95% CI: 1.02-1.79), body mass index (HR = 1.03, 95% CI: 1.01-1.05, per kg/m 2 ), and higher cadmium levels (HR = 1.42, 95% CI: 1.05-1.92, quintile 5 vs. quintiles 1-4) were associated with the 10-year cumulative incidence of HI. There was no association between high lead levels, vitamins D or B12, and 10-year incidence of HI., Conclusions: In addition to age and sex, obesity, education, and blood cadmium levels were associated with increased incidence of HI. These prospective results add to evidence that age-related HI is a multifactorial preventable disorder., Level of Evidence: 2b Laryngoscope, 130:1396-1401, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose Longitudinal population-based cohort data were used to develop a standardized classification system for age-related hearing impairment using thresholds for frequencies (0.5-8 kHz) typically measured in cohort studies. Method Audiometric testing data collected in the Epidemiology of Hearing Loss Study from participants ( n = 1,369) with four visits (1993-1995, 1998-2000, 2003-2005, and 2009-2010) were included (10,952 audiograms). Cluster analyses (Wald's method) were used to identify audiometric patterns. Maximum allowable threshold values were defined for each cluster to create an ordered scale. Progression was defined as a two-step change. Results An eight-step scale was developed to capture audiogram shape and severity of hearing impairment. Of the 1,094 participants classified as having normal hearing based on a pure-tone average, only 25% ( n = 277) were classified as Level 1 (all thresholds ≤ 20 dB HL) on the new scale, whereas 17% ( n = 182) were Levels 4-6. During the 16-year follow-up, 64.9% of those at Level 1 progressed. There was little regression using this scale. Conclusions This is the first scale developed from population-based longitudinal cohort data to capture audiogram shape across time. This simple, standardized scale is easy to apply, reduces misclassification of normal hearing, and may be a useful method for identifying risk factors for early, preclinical, age-related changes in hearing.

Background: Age-related hearing loss (impairment in hearing sensitivity and/or higher-order auditory processing) and cognitive decline are common co-occurring impairments in elderly adults. Their relation in the process of aging remains insufficiently understood. We aim to assess the temporal relations of decline in hearing sensitivity, higher-order auditory processing, and cognition in middle-aged adults., Methods: This study included 1,274 Beaver Dam Offspring Study participants who participated in three examinations (baseline, 5-year, and 10-year follow-up). We assessed hearing sensitivity through pure-tone audiometry (PTA, averaged thresholds of 0.5, 1, 2, 4 kHz of the better ear), higher-order auditory processing as word recognition in competing message (WRCM) using the Northwestern University 6 word list in the better ear, and cognition through trail-making test performance (TMT). Linear mixed-effects models and linear regression models were used to determine associations over time and to what extent these measures influence each other over time., Results: The longitudinal decline between all functions was associated with the strongest relationships between PTA and WRCM. The effect of baseline PTA on WRCM 10 years later (standardized ß = -.30) was almost twice as big as the effect of baseline WRCM on PTA 10 years later (standardized ß = -.18). The effect of baseline WRCM on TMT 10 years later and vice versa were small (standardized ß = -.05). No directional relationship between PTA and TMT was identified (standardized ß ≤ .02)., Conclusions: While hearing sensitivity might affect higher-order auditory processing, associations between hearing and cognition appear bidirectional and weak in midlife. We need to be cautious before inferring causal effects of hearing on cognition., (© The Author(s) 2019. 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.)

Background: Relationships between brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF-1), aldosterone, and cognition in aging were evaluated in the population-based Epidemiology of Hearing Loss Study (1993 to present)., Methods: Beginning in 1998 to 2000, cognitive impairment was assessed by report of physician diagnoses and the Mini-Mental State Examination. In 2009 to 2010 and 2013 to 2016, information was collected on diagnosis of mild cognitive impairment/dementia. Decline in cognitive function was assessed by principal component analysis from additional tests administered during 2009 to 2010 and 2013 to 2016. BDNF, IGF-1, and aldosterone were measured in serum collected in 1998 to 2000., Results: There were 1970 participants (mean age=66.9 y; 59.1% female) without cognitive impairment at baseline. Among women, low BDNF was associated with 16-year incident cognitive impairment [hazard ratio=1.76; 95% confidence interval (CI)=1.04, 2.98]. Among men, increasing IGF-1 was associated with decreased risk [per SD: relative risk (RR)=0.57; 95% CI=0.35, 0.92], whereas increasing aldosterone levels were associated with increased risk (per SD: RR=1.28; 95% CI=1.01, 1.62) for 5-year incident mild cognitive impairment/dementia. Overall, low BDNF was associated with increased risk (RR=1.52; 95% CI=1.02, 2.26) for 5-year cognitive decline., Conclusion: Low levels of serum BDNF and IGF-1 were associated with poorer cognition during aging. There may be differential biomarker effects by sex.

Background: Sensorineural impairments and cardiovascular risk factors (CVRF) and disease (CVD) in midlife may be important predictors of future cognitive health, but longitudinal studies that include multiple sensorineural measures in middle-aged adults are lacking., Methods: Hearing, vision, and olfaction, and CVRF and CVD were measured at the Beaver Dam Offspring Study baseline (2005-2008) examination. The Mini-Mental State Examination and Trail Making Tests A and B were administered at all phases and additional cognitive function measures were obtained at 5 (2010-2013) and 10 years (2015-2017). Cox proportional hazards models were used to evaluate associations between baseline sensorineural impairments, CVRF, CVD, and 10-year cumulative incidence of cognitive impairment and decline., Results: There were 2,556 participants (22-84 years) without cognitive impairment at baseline and data from at least one follow-up. In a multivariable model including age, sex, education, and head injury, visual impairment (hazard ratio = 2.59, 95% confidence interval = 1.34, 5.02), olfactory impairment (hazard ratio = 3.18, 95% confidence interval = 1.53, 6.59), CVD (hazard ratio = 2.37, 95% confidence interval = 1.24, 4.52), and not consuming alcohol in the past year (hazard ratio = 2.21, 95% confidence interval = 1.16, 4.19) were associated with the 10-year cumulative incidence of cognitive impairment. Current smoking and diabetes were associated with increased risk, and exercise with decreased risk, of 10-year decline in cognitive function., Conclusions: Visual and olfactory impairments, CVRF, and CVD were associated with the 10-year cumulative incidence of cognitive impairment and decline in middle-aged adults. Identifying modifiable factors associated with cognitive decline and impairment in midlife may provide opportunities for prevention or treatment and improve cognitive health later in life., (© The Author(s) 2019. 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.)

Objective: Hearing impairment (HI) is common in aging adults. Aldosterone, insulin-like growth factor (IGF1), and brain-derived neurotrophic factor (BDNF) have been identified as potentially protective of hearing. The present study aims to investigate these relationships., Methods: The Epidemiology of Hearing Loss Study is a longitudinal population-based study of aging in Beaver Dam, Wisconsin, that began in 1993. Baseline for the present investigation is the 1998 to 2000 phase. Follow-up exams occurred approximately every 5 years, with the most recent occurring from 2013 to 2016. Hearing was measured by pure-tone audiometry. HI was defined as a pure tone average (PTA) > 25 decibels hearing level in either ear. Change in PTA was the difference between follow-up examinations and baseline. Baseline serum samples were used to measure biomarkers in 2017. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated to assess the effect of biomarker levels in the lowest quintile (Q1) versus the highest (Q5) on incident HI and PTA change., Results: There were 1,088 participants (69.3% women) at risk of HI included in analyses. The mean baseline age was 63.8 years (standard deviation = 7.0). The 16-year incidence of HI was 54.9% and was higher in men (61.1%) than women (52.1%). In age- and sex-adjusted models, aldosterone (HR = 1.06, 95% CI = 0.82-1.37), IGF1 (HR = 0.92, 95% CI = 0.71-1.19), and BDNF (HR = 0.86, 95% CI = 0.66-1.12) levels were not associated with risk of HI. PTA change was similarly not affected by biomarker levels., Conclusion: Aldosterone, IGF1, and BDNF were not associated with decreased risk of age-related hearing loss in this study., Level of Evidence: 2b Laryngoscope, 129:2178-2183, 2019., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Middle age has been identified as a critical time period for health later in life. Identifying factors associated with worse brain function in middle-aged adults may help identify ways to preserve brain function with aging. Our objective was to evaluate factors associated with a novel measure of brain aging in middle-aged and older adults., Design: Longitudinal cohort study., Setting: Beaver Dam Offspring Study (BOSS) baseline (2005-2008), 5-year (2010-2013), and 10-year examinations (2015-2017)., Participants: A total of 2285 adults, 22 to 84 years of age, with complete sensorineural and neurocognitive data at the 5-year examination., Measurements: Principal component analysis (PCA) was performed combining 5-year sensorineural (hearing, vision, olfaction) and cognitive (Trail Making Test A and B, Digit Symbol Substitution Test, Verbal Fluency Test, Auditory Verbal Learning Test) test data. Participants with a standardized PCA score less than -1 were classified as having brain aging. Incident brain aging was defined as a PCA score less than -1 at 10 years among participants who had a PCA score of -1 or higher at 5 years. Logistic regression and Poisson models were used to estimate associations between baseline factors and prevalent or incident brain aging, respectively., Results: Older age, being male, current smoking, larger waist circumference, not consuming alcohol, cardiovascular disease, and interleukin-6 were associated with greater odds of prevalent brain aging, whereas more education and exercise were associated with decreased odds. In addition to age and sex, less than a college education, higher levels of soluble intercellular adhesion molecule-1, diabetes, depressive symptoms, and history of head injury were associated with an increased 5-year risk of incident brain aging., Conclusion: In the current study, vascular and inflammatory factors were associated with a new brain aging marker in middle-aged and older adults. Many of these factors are modifiable, highlighting the importance of addressing health and lifestyle factors in midlife to potentially preserve function for better brain health later in life. J Am Geriatr Soc 67:1610-1616, 2019., (© 2019 The American Geriatrics Society.)

Background: Associations between vascular health-related factors and hearing loss defined using audiometric pure-tone thresholds have been found. Studies have not focused on a potential relationship between vascular health-related factors and central auditory processing., Purpose: The aim of this study was to evaluate, on a population level, the relationship of vascular health-related factors with central auditory function., Research Design: A cross-sectional, population study., Study Sample: Subjects were participants in the Epidemiology of Hearing Loss Study (EHLS) or the Beaver Dam Offspring Study (BOSS)-prospective studies of aging and sensory loss. BOSS participants were the adult offspring of participants in the EHLS. Participants who completed the Dichotic Digits Test (DDT) during the fourth examination period of the EHLS (2008-2010) or the second examination period of the BOSS (2010-2013) were included (n = 3,655, mean age = 61.1 years)., Data Collection and Analysis: The DDT-free recall test was conducted using 25 sets of triple-digit pairs at a 70 dB HL presentation level. The total number of correctly repeated digits from the right and left ears was converted to a percentage correct and used as an outcome. The percentage correct in the left ear was subtracted from the percentage correct in the right ear and used as an outcome. Vascular health-related measures obtained during the examination included blood pressure, mean carotid intima-media thickness, femoral pulse wave velocity (PWV), hemoglobin A1C, and non-high-density lipoprotein (HDL) cholesterol, and, in the EHLS participants, C-reactive protein and interleukin-6. Information on vascular health-related history and behaviors was self-reported. General linear modeling produced estimates of the age- and sex-adjusted least squares means for each vascular factor, and multiple linear regression was used for multivariable modeling of each outcome., Results: After multivariable adjustment, participants with diabetes had a significantly lower (worse) mean DDT-free recall total score (-2.08 percentage points, p < 0.001) than those without diabetes. Participants who exercised at least once per week had a significantly higher (better) mean DDT-free recall total score (+1.07 percentage points, p < 0.01) than those who did not exercise at least once per week. Alcohol consumption was associated with a higher DDT-free recall total score (+0.15 percentage points per +25 g ethanol, p < 0.01). In multivariable modeling of the right-left ear difference in DDT-free recall scores, participants with a history of cardiovascular disease (CVD) or higher PWV demonstrated significantly larger differences (CVD: +3.11 percentage points, p = 0.02; PWV: +0.36 percentage points per 1 m/sec, p < 0.01). Higher levels of non-HDL cholesterol were associated with smaller right-left ear differences (-0.22 percentage points per 10 mg/dL, p = 0.01). Adjustment for handedness did not affect the results., Conclusions: Vascular health-related factors may play a role in central auditory function., (American Academy of Audiology.)

Importance: Hearing impairment (HI) is one of the most common conditions affecting older adults. Identification of factors associated with the development of HI may lead to ways to reduce the incidence of this condition., Objective: To investigate the association between cystatin C, both as an independent biomarker and as a marker of kidney function, and the 20-year incidence of HI., Design, Setting, and Participants: Data were obtained from the Epidemiology of Hearing Loss Study (EHLS), a longitudinal, population-based study in Beaver Dam, Wisconsin. Baseline examinations began in 1993 and continued through 1995, and participants were examined approximately every 5 years, with the most recent examination phase completed in 2015. The EHLS participants with serum cystatin C concentration data and without HI at the baseline examination were included in this study., Main Outcomes and Measures: Participants without HI were followed up for incident HI (pure-tone average of hearing thresholds at 0.5, 1, 2, and 4 kHz >25 dB hearing level in either ear) for 20 years. Cystatin C was analyzed as a biomarker (concentration) and used to determine estimated glomerular filtration rate (eGFRCysC). Discrete-time Cox proportional hazards regression models were used to analyze the association between cystatin C concentration and eGFRCysC and the 20-year cumulative incidence of HI., Results: There were 863 participants aged 48 to 86 years with cystatin C data and without HI at baseline. Of these, 599 (69.4%) were women. In models adjusted for age and sex, cystatin C was associated with an increased risk of developing HI (hazard ratio [HR], 1.20; 95% CI, 1.07-1.34 per 0.2-mg/L increase in cystatin C concentration), but the estimate was attenuated after further adjusting for educational level, current smoking, waist circumference, and glycated hemoglobin (HR, 1.11; 95% CI, 0.98-1.27 per 0.2-mg/L increase in cystatin C concentration). Low eGFRCysC was significantly associated with the 20-year cumulative incidence of HI in both the age- and sex-adjusted model (HR, 1.70; 95% CI, 1.16-2.48; <60 vs ≥60 mL/min/1.73 m2) and the multivariable-adjusted model (HR, 1.50; 95% CI, 1.02-2.22; <60 vs ≥60 mL/min/1.73 m2)., Conclusions and Relevance: Reduced kidney function as estimated using cystatin C, but not cystatin C alone, was associated with the 20-year cumulative incidence of HI, suggesting that some age-related HI may occur in conjunction with or as the result of reduced kidney function.

The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE), a phase 2/3 trial of investigational rVSV∆G-ZEBOV-GP vaccine, was conducted during an unprecedented Ebola epidemic. More than 8600 eligible healthcare and frontline response workers were individually randomized to immediate (within 7 days) or deferred (within 18-24 weeks) vaccination and followed for 6 months after vaccination for serious adverse events and Ebola virus infection. Key challenges included limited infrastructure to support trial activities, unreliable electricity, and staff with limited clinical trial experience. Study staff made substantial infrastructure investments, including renovation of enrollment sites, laboratories, and government cold chain facilities, and imported equipment to store and transport vaccine at ≤-60oC. STRIVE built capacity by providing didactic and practical research training to >350 staff, which was reinforced with daily review and feedback meetings. The operational challenges of safety follow-up were addressed by issuing mobile telephones to participants, making home visits, and establishing a nurse triage hotline. Before the Ebola outbreak, Sierra Leone had limited infrastructure and staff to conduct clinical trials. Without interfering with the outbreak response, STRIVE responded to an urgent need and helped build this capacity., Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Background: Hearing, visual, and olfactory impairments have been associated with cognitive impairment in older adults but less is known about associations with cognitive function in middle-aged adults., Methods: Sensory and cognitive functions were measured on participants in the baseline examination (2005-2008) of the Beaver Dam Offspring Study. Cognitive function was measured with the Trail Making tests A (TMTA) and B (TMTB) and the Grooved Peg Board test. Pure-tone audiometry, Pelli-Robson letter charts, and the San Diego Odor Identification test were used to measure hearing, contrast sensitivity, and olfaction, respectively., Results: There were 2,836 participants aged 21-84 years with measures of hearing, visual, olfactory, and cognitive function at the baseline examination. Nineteen percent of the cohort had one sensory impairment and 3% had multiple sensory impairments. In multivariable adjusted linear regression models that included all three sensory impairments, hearing impairment, visual impairment, and olfactory impairment were each independently associated with poorer performance on the TMTA, TMTB, and Grooved Peg Board (p < .05 for all sensory impairments in all models). Participants with a sensory impairment took on average from 2 to 10 seconds longer than participants without the corresponding sensory impairment to complete these tests. Results were similar in models that included adjustment for hearing aid use., Conclusion: Hearing, visual and olfactory impairment were associated with poorer performance on cognitive function tests independent of the other sensory impairments and factors associated with cognition. Sensory impairments in midlife are associated with subtle deficits in cognitive function which may be indicative of early brain aging., (© The Author 2017. 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.)

Objectives/hypothesis: To measure odor detection thresholds and associated nasal and behavioral factors in an older adult population., Study Design: Cross-sectional cohort study., Methods: Odor detection thresholds were obtained using an automated olfactometer on 832 participants, aged 68 to 99 (mean age = 77) years in the 21-year (2013-2016) follow-up visit of the Epidemiology of Hearing Loss Study., Results: The mean odor detection threshold (ODT) score was 8.2 (range = 1-13; standard deviation = 2.54), corresponding to an n-butanol concentration of slightly less than 0.03%. Older participants were significantly more likely to have lower (worse) ODT scores than younger participants (P < .001). There were no significant differences in mean ODT scores between men and women. Older age was significantly associated with worse performance in multivariable regression models, and exercising at least once per week was associated with reduced odds of having a low (≤5) ODT score. Cognitive impairment was also associated with poor performance, whereas a history of allergies or a deviated septum was associated with better performance., Conclusions: Odor detection threshold scores were worse in older age groups but similar between men and women in this large population of older adults. Regular exercise was associated with better odor detection thresholds, adding to the evidence that decline in olfactory function with age may be partly preventable., Level of Evidence: 3b. Laryngoscope, 127:1257-1262, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Sensory impairments increase with age and the majority of older people will experience a sensory impairment if they live long enough. However, the relationships of hearing, visual, and olfactory impairments with mortality are not well understood., Methods: Epidemiology of Hearing Loss Study participants (n = 2,418) aged 53-97 years (mean = 69 years) were examined in 1998-2000 and hearing, visual acuity, and olfaction were measured. Participants were followed for mortality for up to 17 years (mean = 12.8 years). Cox proportional hazards models were used to assess the association between prevalent sensory impairments and the 15-year cumulative incidence of death., Results: A total of 1,099 (45.4%) of participants died during the follow-up period. In age- and sex-adjusted Cox models, the risk of mortality was higher among participants with one (hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.19, 1.64) or two or more (HR = 2.12, 95% CI = 1.74, 2.58) sensory impairments than among participants with no sensory impairments. Olfactory impairment at baseline was significantly associated with mortality (HR = 1.28, 95% CI = 1.07, 1.52) after adjusting for age, sex, sensory comorbidities, cardiovascular risk factors and disease, cognitive impairment, frailty, subclinical atherosclerosis, and inflammatory marker levels (n = 1,745). Hearing and visual impairment were not associated with mortality after adjusting for subclinical atherosclerosis and inflammation., Conclusion: Olfactory impairment, but not hearing or visual impairment, was associated with an increased risk of mortality. These results suggest that olfactory impairment may be a marker of underlying physiologic processes or pathology that is associated with aging and reduced survival in older adults., (© The Author 2016. 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.)

Objectives: The Dichotic Digits test (DDT) has been widely used to assess central auditory processing but there is limited information on observed DDT performance in a general population. The purpose of the study was to determine factors related to DDT performance in a large cohort spanning the adult age range., Design: The study was cross-sectional and subjects were participants in the Epidemiology of Hearing Loss Study (EHLS), a population-based investigation of age-related hearing loss, or the Beaver Dam Offspring Study (BOSS), a study of aging in the adult offspring of the EHLS members. Subjects seen during the 4th EHLS (2008 to 2010) or the 2nd BOSS (2010 to 2013) examination were included (N = 3655 participants [1391 EHLS, 2264 BOSS]; mean age = 61.1 years, range = 21 to 100 years). The free and right ear-directed recall DDTs were administered using 25 sets of triple-digit pairs with a 70 dB HL presentation level. Pure-tone audiometric testing was conducted and the pure-tone threshold average (PTA) at 0.5, 1, 2, and 4 kHz was categorized using the worse ear: no loss = PTA ≤ 25 dB HL; mild loss = 25 < PTA ≤ 40 dB HL; moderate or marked loss = PTA > 40 dB HL. Cognitive impairment was defined as a Mini-Mental State Examination score < 24 (maximum = 30) or a self- or proxy-reported history of dementia or Alzheimer's disease. Demographic information was self-reported. General linear models were fit and multiple linear regression was performed., Results: The mean total free recall DDT score was 76.7% (range = 21.3 to 100%). Less than 10% of the participants had a total free recall score below 60% correct. The mean right ear-directed recall score was 98.4% with 69% of the participants scoring 100% and another 15.5% scoring 98.7% (1 incorrect digit). In multivariable modeling of the total free recall scores, the predicted mean free recall score was 1 percentage point lower for every 5-year increase in age, 2.3 percentage points lower in males than females, 8.7 percentage points lower in participants with less than a high school degree than in those with college degrees, 6.8 percentage points lower in participants with a moderate or marked hearing loss compared with no hearing loss, and 8.3 percentage points lower in participants with cognitive impairment compared with those without cognitive impairment. These 5 factors were independently and significantly related to performance and accounted for 22.7% of the total variability in free recall scores., Conclusions: Substantial variation in the total free recall DDT scores but very little variation in the right ear-directed recall DDT scores was observed. Age, sex, education, hearing loss severity, and cognitive impairment were found to be significantly related to DDT scores but explained less than 25% of the total variability in total free recall scores. The right ear-directed recall DDT by itself may not be of benefit in assessing central auditory processing in a general population because of its limited variability but further evaluation of factors potentially related to free recall DDT variability may prove useful.

Objective: The aim of this study is to examine, by a prospective randomized controlled trial, the influence of liberal (LIB) vs restricted (RES) perioperative fluid administration on morbidity following pancreatectomy., Summary of Background Data: Randomized controlled trials in patients undergoing major intra-abdominal surgery have challenged the historical use of LIB fluid administration, suggesting that a more restricted regimen may be associated with fewer postoperative complications., Methods: Patients scheduled to undergo pancreatic resection were consented for randomization to a LIB (n = 164) or RES (n = 166) perioperative fluid regimen. Sample size was designed with 80% power to decrease Grade 3 complications from 35% to 21%., Results: Between July 2009 and July 2015, we randomized 330 patients undergoing pancreaticoduodenectomy (PD, n = 218), central (n = 16), or distal pancreatectomy (DP, n = 96). Patients were equally distributed for all demographic and intraoperative characteristics. Intraoperatively, LIB patients received crystalloid 12 mL/kg/h and RES patients 6 mL/kg/h. Cumulative crystalloid given (median, range, mL) days 0 to 3 was LIB: 12,252 (6600 to 21,365), RES 7808 (2700 to 16,274) P < 0.0001. Sixty-day mortality was 2 of 330 (0.6%). Median operative time for PD was 227 minutes (105 to 462) and DP 150 (44 to 323). Grade 3 complications occurred in 20% of LIB and 27% of RES patients (P = 0.6). Median length of stay was 7 and 5 days for PD and DP, respectively, in both arms., Conclusions: In a high volume institution, major perioperative complications from pancreatic resection were not significantly influenced by fluid regimens that differed approximately 1.6-fold., Competing Interests: The authors declare no conflicts of interest.

Objectives: To evaluate the associations between sensory impairments and 10-year risk of cognitive impairment., Design: The Epidemiology of Hearing Loss Study (EHLS), a longitudinal, population-based study of aging in the Beaver Dam, Wisconsin community. Baseline examinations were conducted in 1993 and follow-up examinations have been conducted every 5 years., Setting: General community., Participants: EHLS members without cognitive impairment at EHLS-2 (1998-2000). There were 1,884 participants (mean age 66.7) with complete EHLS-2 sensory data and follow-up information., Measurements: Cognitive impairment was defined as a Mini-Mental State Examination score of <24 or history of dementia or Alzheimer's disease. Hearing impairment was a pure-tone average of hearing thresholds (0.5, 1, 2, 4 kHz) of >25 dB hearing level in either ear, visual impairment was a Pelli-Robson contrast sensitivity of <1.55 log units in the better eye, and olfactory impairment was a San Diego Odor Identification Test score of <6., Results: Hearing, visual, and olfactory impairment were independently associated with cognitive impairment risk (hearing: hazard ratio (HR) = 1.90, 95% confidence interval (CI) = 1.11-3.26; vision: HR = 2.05, 95% CI = 1.24-3.38; olfaction: HR = 3.92, 95% CI = 2.45-6.26)). Nevertheless, 85% of participants with hearing impairment, 81% with visual impairment, and 76% with olfactory impairment did not develop cognitive impairment during follow-up., Conclusion: The relationship between sensory impairment and cognitive impairment was not unique to one sensory system, suggesting that sensorineural health may be a marker of brain aging. The development of a combined sensorineurocognitive measure may be useful in uncovering mechanisms of healthy brain aging., Competing Interests: Disclosures: Elements of Financial/Personal Conflicts MEF KJC CRS AAP Yes No Yes No Yes No Yes No Employment or Affiliation X X X X Grants/Funds X X X X Honoraria X X X X Speaker Forum X X X X Consultant X X X X Stocks X X X X Royalties X X X X Expert Testimony X X X X Board Member X X X X Patents X X X X Personal Relationship X X X X Elements of Financial/Personal Conflicts CMC BEKK RK TST Yes No Yes No Yes No Yes No Employment or Affiliation X X X X Grants/Funds X X X X Honoraria X X X X Speaker Forum X X X X Consultant X X X X Stocks X X X X Royalties X X X X Expert Testimony X X X X Board Member X X X X Patents X X X X Personal Relationship X X X X output.txt Authors can be listed by abbreviations of their names. For “yes” x mark(s): give brief explanation below:, (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

Nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent dementia, but previous studies have yielded conflicting results. This study estimated the association of prior NSAID use with incident cognitive impairment in the population-based Epidemiology of Hearing Loss Study (EHLS, n=2422 without cognitive impairment in 1998-2000). Prospectively collected medication data from 1988-1990, 1993-1995, and 1998-2000 were used to categorize NSAID use history at the cognitive baseline (1998-2000). Aspirin use and nonaspirin NSAID use were separately examined. Cox regression models were used to estimate the associations between NSAID use history at baseline and incident cognitive impairment in 2003-2005 or 2009-2010. Logistic regression analyses were used to estimate associations with a second outcome, mild cognitive impairment/dementia, available in 2009-2010. Participants using aspirin at baseline but not 5 years prior were more likely to develop cognitive impairment (adjusted hazard ratio=1.77; 95% confidence interval=1.11, 2.82; model 2), with nonsignificant associations for longer term use. Nonaspirin NSAID use was not associated with incident cognitive impairment or mild cognitive impairment/dementia odds. These results provided no evidence to support a potential protective effect of NSAIDs against dementia.

Although a vaccine against hepatitis B virus (HBV) has been available since 1982, it is estimated that 600,000 people die every year due to HBV. An affordable oral vaccine could help alleviate the disease burden and to this end the hepatitis B surface antigen (HBsAg) was expressed in maize. Orally delivered maize material induced the strongest immune response in mice when lipid was extracted by CO2 supercritical fluid extraction (SFE), compared to full fat and hexane-extracted material. The present study provides a biochemical and biophysical basis for these immunological differences by comparing the active ingredient in the differently treated maize material. Purified maize-derived HBsAg underwent biophysical characterization by gel filtration, transmission electron microscopy (TEM), dynamic light scattering (DLS), UV-CD, and fluorescence. Gel filtration showed that HBsAg forms higher-order oligomers and TEM demonstrated virus-like particle (VLP) formation. The VLPs obtained from SFE were more regular in shape and size compared to hexane or full fat material. In addition, SFE-derived HBsAg showed the greatest extent of α-helical structure by far UV-CD spectrum. Fluorescence experiments also revealed differences in protein conformation. This work establishes SFE-treated maize material as a viable oral vaccine candidate and advances the development of the first oral subunit vaccine., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Clinicians encounter patients who report experiencing hearing difficulty (HD) even when audiometric thresholds fall within normal limits. When there is no evidence of audiometric hearing loss, it generates debate over possible biomedical and psychosocial etiologies. It is possible that self-reported HDs relate to variables within and/or outside the scope of audiology. The purpose of this study is to identify how often, on a population basis, people with normal audiometric thresholds self-report HD and to identify factors associated with such HDs., Design: This was a cross-sectional investigation of participants in the Beaver Dam Offspring Study. HD was defined as a self-reported HD on a four-item scale despite having pure-tone audiometric thresholds within normal limits (<20 dB HL0.5, 1, 2, 3, 4, 6, 8 kHz bilaterally, at each frequency). Distortion product otoacoustic emissions and word-recognition performance in quiet and with competing messages were also analyzed. In addition to hearing assessments, relevant factors such as sociodemographic and lifestyle factors, environmental exposures, medical history, health-related quality of life, and symptoms of neurological disorders were also examined as possible risk factors. The Center for Epidemiological Studies-Depression was used to probe symptoms associated with depression, and the Medical Outcomes Study Short-Form 36 mental score was used to quantify psychological stress and social and role disability due to emotional problems. The Visual Function Questionnaire-25 and contrast sensitivity test were used to query vision difficulties., Results: Of the 2783 participants, 686 participants had normal audiometric thresholds. An additional grouping variable was created based on the available scores of HD (four self-report questions), which reduced the total dataset to n = 682 (age range, 21-67 years). The percentage of individuals with normal audiometric thresholds who self-reported HD was 12.0% (82 of 682). The prevalence in the entire cohort was therefore 2.9% (82 of 2783). Performance on audiological tests (distortion product otoacoustic emissions and word-recognition tests) did not differ between the group self-reporting HD and the group reporting no HD. A multivariable model controlling for age and sex identified the following risk factors for HD: lower incomes (odds ratio [OR] $50,000+ = 0.55, 95% confidence interval [CI] = 0.30-1.00), noise exposure through loud hobbies (OR = 1.48, 95% CI = 1.15-1.90), or firearms (OR = 2.07, 95% CI = 1.04-4.16). People reporting HD were more likely to have seen a doctor for hearing loss (OR = 12.93, 95% CI = 3.86-43.33) and report symptoms associated with depression (Center for Epidemiological Studies-Depression [OR = 2.39, 95% CI = 1.03-5.54]), vision difficulties (Visual Function Questionnaire-25 [OR = 0.93, 95% CI = 0.89-0.97]), and neuropathy (e.g., numbness, tingling, and loss of sensation [OR = 1.98, 95% CI = 1.14-3.44])., Conclusions: The authors used a population approach to identify the prevalence and risk factors associated with self-reported HD among people who perform within normal limits on common clinical tests of auditory function. The percentage of individuals with normal audiometric thresholds who self-reported HD was 12.0%, resulting in an overall prevalence of 2.9%. Auditory and nonauditory risk factors were identified, therefore suggesting that future directions aimed at assessing, preventing, and managing these types of HDs might benefit from information outside the traditional scope of audiology.

Background: the incidence of olfactory impairment increases sharply in the eighth and ninth decades of life but the aetiology of age-related olfactory decline is not well understood. Inflammation and atherosclerosis are associated with many age-related conditions and atherosclerosis has been associated with olfactory decline in middle-aged adults., Objective: to determine if inflammatory markers and atherosclerosis are associated with the development of olfactory impairment in older adults., Design: longitudinal, population-based study., Setting/participants: a total of 1,611 participants, aged 53-97 years in the Epidemiology of Hearing Loss Study without olfactory impairment at the 1998-2000 examination and with follow-up at a subsequent examination 5 and/or 10 years later., Methods: the San Diego Odor Identification Test was used to measure olfaction. High sensitivity C-reactive protein, interleukin-6 and tumour necrosis factor-α were measured in serum and carotid ultrasound images were obtained for the measurement of carotid intima media thickness (IMT) and plaque assessment. Medical history, behavioural and lifestyle information were obtained by interview., Results: inflammatory markers, IMT and plaque were not associated with the 10-year cumulative incidence of olfactory impairment in adjusted Cox proportional hazard models. Among those <60 years, the mean IMT [hazard ratio (HR) = 4.35, 95% confidence interval (CI) = 1.69-11.21, tertile 3 versus tertile 1] and the number of sites with plaque (HR = 1.56, 95% CI = 1.17-2.08, per site) were associated with an increased risk of developing an olfactory impairment at follow-up., Conclusion: subclinical atherosclerosis at a younger age may be a risk factor for the development of olfactory impairment., (© The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

In 2004 the European Commission and Member States initiated activities towards a harmonized approach for Human Biomonitoring surveys throughout Europe. The main objective was to sustain environmental health policy by building a coherent and sustainable framework and by increasing the comparability of data across countries. A pilot study to test common guidelines for setting up surveys was considered a key step in this process. Through a bottom-up approach that included all stakeholders, a joint study protocol was elaborated. From September 2011 till February 2012, 17 European countries collected data from 1844 mother-child pairs in the frame of DEMOnstration of a study to COordinate and Perform Human Biomonitoring on a European Scale (DEMOCOPHES).(1) Mercury in hair and urinary cadmium and cotinine were selected as biomarkers of exposure covered by sufficient analytical experience. Phthalate metabolites and Bisphenol A in urine were added to take into account increasing public and political awareness for emerging types of contaminants and to test less advanced markers/markers covered by less analytical experience. Extensive efforts towards chemo-analytical comparability were included. The pilot study showed that common approaches can be found in a context of considerable differences with respect to experience and expertize, socio-cultural background, economic situation and national priorities. It also evidenced that comparable Human Biomonitoring results can be obtained in such context. A European network was built, exchanging information, expertize and experiences, and providing training on all aspects of a survey. A key challenge was finding the right balance between a rigid structure allowing maximal comparability and a flexible approach increasing feasibility and capacity building. Next steps in European harmonization in Human Biomonitoring surveys include the establishment of a joint process for prioritization of substances to cover and biomarkers to develop, linking biomonitoring surveys with health examination surveys and with research, and coping with the diverse implementations of EU regulations and international guidelines with respect to ethics and privacy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The potential of Human Biomonitoring (HBM) in exposure characterisation and risk assessment is well established in the scientific HBM community and regulatory arena by many publications. The European Environment and Health Strategy as well as the Environment and Health Action Plan 2004-2010 of the European Commission recognised the value of HBM and the relevance and importance of coordination of HBM programmes in Europe. Based on existing and planned HBM projects and programmes of work and capabilities in Europe the Seventh Framework Programme (FP 7) funded COPHES (COnsortium to Perform Human Biomonitoring on a European Scale) to advance and improve comparability of HBM data across Europe. The pilot study protocol was tested in 17 European countries in the DEMOCOPHES feasibility study (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale) cofunded (50%) under the LIFE+ programme of the European Commission. The potential of HBM in supporting and evaluating policy making (including e.g. REACH) and in awareness raising on environmental health, should significantly advance the process towards a fully operational, continuous, sustainable and scientifically based EU HBM programme. From a number of stakeholder activities during the past 10 years and the national engagement, a framework for sustainable HBM structure in Europe is recommended involving national institutions within environment, health and food as well as European institutions such as ECHA, EEA, and EFSA. An economic frame with shared cost implications for national and European institutions is suggested benefitting from the capacity building set up by COPHES/DEMOCOPHES., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In 2011 and 2012, the COPHES/DEMOCOPHES twin projects performed the first ever harmonized human biomonitoring survey in 17 European countries. In more than 1800 mother-child pairs, individual lifestyle data were collected and cadmium, cotinine and certain phthalate metabolites were measured in urine. Total mercury was determined in hair samples. While the main goal of the COPHES/DEMOCOPHES twin projects was to develop and test harmonized protocols and procedures, the goal of the current paper is to investigate whether the observed differences in biomarker values among the countries implementing DEMOCOPHES can be interpreted using information from external databases on environmental quality and lifestyle. In general, 13 countries having implemented DEMOCOPHES provided high-quality data from external sources that were relevant for interpretation purposes. However, some data were not available for reporting or were not in line with predefined specifications. Therefore, only part of the external information could be included in the statistical analyses. Nonetheless, there was a highly significant correlation between national levels of fish consumption and mercury in hair, the strength of antismoking legislation was significantly related to urinary cotinine levels, and we were able to show indications that also urinary cadmium levels were associated with environmental quality and food quality. These results again show the potential of biomonitoring data to provide added value for (the evaluation of) evidence-informed policy making., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Susceptibility to environmental stressors has been described for fetal and early childhood development. However, the possible susceptibility of the prepubertal period, characterized by the orchestration of the organism towards sexual maturation and adulthood has been poorly investigated and exposure data are scarce. In the current study levels of cadmium (Cd), cotinine and creatinine in urine were analyzed in a subsample 216 children from 12 European countries within the DEMOCOPHES project. The children were divided into six age-sex groups: boys (6-8 years, 9-10 years and 11 years old), and girls (6-7 years, 8-9 years, 10-11 years). The number of subjects per group was between 23 and 53. The cut off values were set at 0.1 µg/L for Cd, and 0.8 µg/L for cotinine defined according to the highest limit of quantification. The levels of Cd and cotinine were adjusted for creatinine level. In the total subsample group, the median level of Cd was 0.180 µg/L (range 0.10-0.69 µg/L), and for cotinine the median wet weight value was 1.50 µg/L (range 0.80-39.91 µg/L). There was no significant difference in creatinine and cotinine levels between genders and age groups. There was a significant correlation between levels of cadmium and creatinine in all children of both genders. This shows that even at such low levels the possible effect of cadmium on kidney function was present and measurable. An increase in Cd levels was evident with age. Cadmium levels were significantly different between 6-7 year old girls, 11 year old boys and 10-11 year old girls. As there was a balanced distribution in the number of subjects from countries included in the study, bias due to data clustering was not probable. The impact of low Cd levels on kidney function and gender differences in Cd levels needs further investigation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Within the European Environment and Health Action Plan an initiative to establish a coherent human biomonitoring approach in Europe was started. The project COPHES (COnsortium to Perform Human biomonitoring on a European Scale ) developed recommendations for a harmonized conduct of a human biomonitoring (HBM) survey which came into action as the pilot study DEMOCOPHES (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale). Seventeen European countries conducted a survey with harmonized instruments for, inter alia, recruitment, fieldwork and sampling, in autumn/winter 2011/2012. Based on the countries' experiences of conducting the pilot study, following lessons learnt were compiled: the harmonized fieldwork instruments (basic questionnaire, urine and hair sampling) turned out to be very valuable for future HBM surveys on the European scale. A school approach was favoured by most of the countries to recruit school-aged children according to the established guidelines and country specific experiences. To avoid a low participation rate, intensive communication with the involved institutions and possible participants proved to be necessary. The communication material should also include information on exclusion criteria and offered incentives. Telephone contact to the participants the day before fieldwork during the survey can prevent the forgetting of appointments and first morning urine samples. To achieve comparable results on the European scale, training of interviewers in all issues of recruitment, fieldwork and sampling through information material and training sessions is crucial. A survey involving many European countries needs time for preparation and conduct. Materials for quality control prepared for all steps of recruitment, fieldwork and sampling proved to be important to warrant reliable results., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Human biomonitoring (HBM) is an effective tool for assessing actual exposure to chemicals that takes into account all routes of intake. Although hair analysis is considered to be an optimal biomarker for assessing mercury exposure, the lack of harmonization as regards sampling and analytical procedures has often limited the comparison of data at national and international level. The European-funded projects COPHES and DEMOCOPHES developed and tested a harmonized European approach to Human Biomonitoring in response to the European Environment and Health Action Plan. Herein we describe the quality assurance program (QAP) for assessing mercury levels in hair samples from more than 1800 mother-child pairs recruited in 17 European countries. To ensure the comparability of the results, standard operating procedures (SOPs) for sampling and for mercury analysis were drafted and distributed to participating laboratories. Training sessions were organized for field workers and four external quality-assessment exercises (ICI/EQUAS), followed by the corresponding web conferences, were organized between March 2011 and February 2012. ICI/EQUAS used native hair samples at two mercury concentration ranges (0.20-0.71 and 0.80-1.63) per exercise. The results revealed relative standard deviations of 7.87-13.55% and 4.04-11.31% for the low and high mercury concentration ranges, respectively. A total of 16 out of 18 participating laboratories the QAP requirements and were allowed to analyze samples from the DEMOCOPHES pilot study. Web conferences after each ICI/EQUAS revealed this to be a new and effective tool for improving analytical performance and increasing capacity building. The procedure developed and tested in COPHES/DEMOCOPHES would be optimal for application on a global scale as regards implementation of the Minamata Convention on Mercury., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The toxicity of methylmercury (MeHg) in humans is well established and the main source of exposure is via the consumption of large marine fish and mammals. Of particular concern are the potential neurodevelopmental effects of early life exposure to low-levels of MeHg. Therefore, it is important that pregnant women, children and women of childbearing age are, as far as possible, protected from MeHg exposure. Within the European project DEMOCOPHES, we have analyzed mercury (Hg) in hair in 1799 mother-child pairs from 17 European countries using a strictly harmonized protocol for mercury analysis. Parallel, harmonized questionnaires on dietary habits provided information on consumption patterns of fish and marine products. After hierarchical cluster analysis of consumption habits of the mother-child pairs, the DEMOCOPHES cohort can be classified into two branches of approximately similar size: one with high fish consumption (H) and another with low consumption (L). All countries have representatives in both branches, but Belgium, Denmark, Spain, Portugal and Sweden have twice as many or more mother-child pairs in H than in L. For Switzerland, Czech Republic, Hungary, Poland, Romania, Slovenia and Slovakia the situation is the opposite, with more representatives in L than H. There is a strong correlation (r=0.72) in hair mercury concentration between the mother and child in the same family, which indicates that they have a similar exposure situation. The clustering of mother-child pairs on basis of their fish consumption revealed some interesting patterns. One is that for the same sea fish consumption, other food items of marine origin, like seafood products or shellfish, contribute significantly to the mercury levels in hair. We conclude that additional studies are needed to assess and quantify exposure to mercury from seafood products, in particular. The cluster analysis also showed that 95% of mothers who consume once per week fish only, and no other marine products, have mercury levels 0.55 μg/g. Thus, the 95th percentile of the distribution in this group is only around half the US-EPA recommended threshold of 1 μg/g mercury in hair. Consumption of freshwater fish played a minor role in contributing to mercury exposure in the studied cohort. The DEMOCOPHES data shows that there are significant differences in MeHg exposure across the EU and that exposure is highly correlated with consumption of fish and marine products. Fish and marine products are key components of a healthy human diet and are important both traditionally and culturally in many parts of Europe. Therefore, the communication of the potential risks of mercury exposure needs to be carefully balanced to take into account traditional and cultural values as well as the potential health benefits from fish consumption. European harmonized human biomonitoring programs provide an additional dimension to national HMB programs and can assist national authorities to tailor mitigation and adaptation strategies (dietary advice, risk communication, etc.) to their country's specific requirements., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

A communication strategy was developed by The Consortium to Perform Human Biomonitoring on a European Scale (COPHES), as part of its objectives to develop a framework and protocols to enable the collection of comparable human biomonitoring data throughout Europe. The framework and protocols were tested in the pilot study DEMOCOPHES (Demonstration of a study to Coordinate and Perform Human biomonitoring on a European Scale). The aims of the communication strategy were to raise awareness of human biomonitoring, encourage participation in the study and to communicate the study results and their public health significance. It identified the audiences and key messages, documented the procedure for dissemination of results and was updated as the project progressed. A communication plan listed the tools and materials such as press releases, flyers, recruitment letters and information leaflets required for each audience with a time frame for releasing them. Public insight research was used to evaluate the recruitment material, and the feedback was used to improve the documents. Dissemination of results was coordinated in a step by step approach by the participating countries within DEMOCOPHES, taking into account specific national messages according to the needs of each country. Participants received individual results, unless they refused to be informed, along with guidance on what the results meant. The aggregate results and policy recommendations were then communicated to the general public and stakeholders, followed by dissemination at European level. Several lessons were learnt that may assist other future human biomonitoring studies. Recruitment took longer than anticipated and so social scientists, to help with community engagement, should be part of the research team from the start. As a European study, involving multiple countries, additional considerations were needed for the numerous organisations, different languages, cultures, policies and priorities. Therefore, communication documents should be seen as templates with essential information clearly indicated and the option for each country to tailor the material to reflect these differences. Future studies should consider setting up multidisciplinary networks of medical professionals and communication experts, and holding training workshops to discuss the interpretation of results and risk communication. Publicity and wide dissemination of the results helped to raise awareness of human biomonitoring to the general public, policy makers and other key stakeholders. Effective and timely communication, at all stages of a study, is essential if the potential of human biomonitoring research to improve public health is to be realised., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

The metal cadmium (Cd) is a widespread environmental pollutant with documented adverse effects on the kidneys and bones from long-term environmental exposure, but with insufficiently elucidated public health consequences such as risk of cardiovascular disease, hormone-related cancer in adults and developmental effects in children. This study is the first pan-European human biomonitoring project that succeeded in performing harmonized measurements of Cd in urine in a comparable way in mother-child couples from 16 European countries. The aim of the study was to evaluate the overall Cd exposure and significant determinants of Cd exposure. A study population of 1632 women (24-52 years of age), and 1689 children (5-12 years of age), from 32 rural and urban areas, was examined within a core period of 6 months in 2011-2012. Women were stratified as smokers and non-smokers. As expected, smoking mothers had higher geometric mean (gm) urinary cadmium (UCd; 0.24 µg/g crea; n=360) than non-smoking mothers (gm 0.18 µg/g crea; n=1272; p<0.0001), and children had lower UCd (gm 0.065 µg/g crea; n=1689) than their mothers at the country level. Non-smoking women exposed to environmental tobacco smoke (ETS) at home had 14% (95% CI 1-28%) higher UCd than those who were not exposed to ETS at home (p=0.04). No influence of ETS at home or other places on UCd levels was detected in children. Smoking women with primary education as the highest educational level of the household had 48% (95% CI 18-86%) higher UCd than those with tertiary education (p=0.0008). The same observation was seen in non-smoking women and in children; however they were not statistically significant. In children, living in a rural area was associated with 7% (95% CI 1-13%) higher UCd (p=0.03) compared to living in an urban area. Children, 9-12 years had 7% (95% CI 1-13%) higher UCd (p=0.04) than children 5-8 years. About 1% of the mothers, and 0.06% of the children, exceeded the tolerable weekly intake (TWI) appointed by EFSA, corresponding to 1.0 µg Cd/g crea in urine. Poland had the highest UCd in comparison between the 16 countries, while Denmark had the lowest. Whether the differences between countries are related to differences in the degree of environmental Cd contamination or to differences in lifestyle, socioeconomic status or dietary patterns is not clear., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to determine if subclinical markers of atherosclerosis are associated with a decline in olfactory function., Methods: The San Diego Odor Identification Test was administered to 2,302 participants (age 21-84 years) at the baseline (2005-2008) and 5-year follow-up (2010-2013) examinations of the Beaver Dam Offspring Study. A decline in odor identification was defined as a decrease in San Diego Odor Identification Test score of 2 or more (range 0-8) from Beaver Dam Offspring Study 1 to Beaver Dam Offspring Study 2. Carotid intima media thickness and plaque, blood pressure, pulse wave velocity, and body mass index were measured and other risk factor data were obtained by interview., Results: Overall 3.2% of participants had a decline in San Diego Odor Identification Test score at 5 years. In age- and sex-adjusted models, mean intima media thickness (odds ratio = 1.17, 95% CI = 1.01, 1.34, per 0.1 mm) and number of sites (range 0-6) with carotid artery plaque (odds ratio = 1.35, 95% CI = 1.11, 1.65, per site) at baseline were associated with an increased risk for decline. Plaque score (odds ratio = 1.24, 95% CI = 1.01, 1.53) remained a significant independent predictor of olfactory decline in a model that included age, sex, hypertension, body mass index, alcohol, and smoking., Conclusions: Subclinical atherosclerosis was associated with an increased risk for olfactory decline indicating that atherosclerosis may be one of the risk factors for the decline in olfactory function seen with aging. Strategies to improve vascular health may also benefit olfactory health., (© The Author 2014. 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.)

Background: The hepatitis B surface antigen (HBsAg) has been administered over the last 20 years as a parenteral vaccine against the hepatitis B virus (HBV). Despite high seroconversion rates, chronic infection rates are still high worldwide. Orally delivered vaccines provide a practical alternative to injected vaccines, potentially helping poorly responding populations and providing a viable alternative for populations in remote locations. Anamnestic responses are vital to establishing the efficacy of a given vaccine and have been assessed in this study using a plant-based oral delivery platform expressing HBsAg., Methods: Long-term immunological memory was assessed in mice injected with a primary dose of Recombivax and boosted with orally-delivered HBsAg wafers, control wafers, or parenterally-delivered commercial vaccine (Recombivax)., Results: Mice boosted with HBsAg orally-administered wafers displayed sharp increases in mucosal IgA titers in fecal material and steep increases in serum IgA, whereas mice boosted with Recombivax showed no detectable levels of IgA in either fecal or serum samples following four boosting treatments. Long-term memory in the orally-treated mice was evidenced by sustained fecal IgA, and serum IgA, IgG, and mIU/mL over one year, while Recombivax-treated mice displayed sustained serum IgG and mIU/mL. Furthermore, sharp increases in these same antibodies were induced after re-boosting at 47 and 50 weeks post-primary injection., Conclusions: Orally-delivered vaccines can provide long-term immune responses mucosally and systemically. For sexually-transmitted diseases that can be acquired at mucosal surfaces, such as HBV, an oral delivery platform may provide added protection over a conventional parenterally administered vaccine., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: To determine associations between smoking, adiposity, diabetes mellitus, and other risk factors for cardiovascular disease (CVD) and the 15-year incidence of hearing impairment (HI)., Design: A longitudinal population-based cohort study (1993-95 to 2009-10), the Epidemiology of Hearing Loss Study (EHLS)., Setting: Beaver Dam, Wisconsin., Participants: Participants in the Beaver Dam Eye Study (1988-90; residents of Beaver Dam, WI, aged 43-84 in 1987-88) were eligible for the EHLS. There were 1,925 participants with normal hearing at baseline., Measurements: Fifteen-year cumulative incidence of HI (pure-tone average of hearing thresholds at 0.5, 1, 2, and 4 kHz greater than 25 decibels hearing level in either ear). Cigarette smoking, exercise, and other factors were ascertained according to questionnaire. Blood pressure, waist circumference, body mass index, and glycosylated hemoglobin were measured., Results: Follow-up examinations (≥1) were obtained from 87.2% (n=1,678; mean baseline age 61). The 15-year cumulative incidence of HI was 56.8%. Adjusting for age and sex, current smoking (hazard ratio (HR)=1.31, P=.048), education (<16 years; HR=1.35, P=.01), waist circumference (HR=1.08 per 10 cm, P=.02), and poorly controlled diabetes mellitus (HR=2.03, P=.048) were associated with greater risk of HI. Former smokers and people with better-controlled diabetes mellitus were not at greater risk., Conclusion: Smoking, central adiposity, and poorly controlled diabetes mellitus predicted incident HI. These well-known risk factors for CVD suggest that vascular changes may contribute to HI in aging. Interventions targeting reductions in smoking and adiposity and better glycemic control in people with diabetes mellitus may help prevent or delay the onset of HI., (© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.)

Background: For Europe as a whole, data on internal exposure to environmental chemicals do not yet exist. Characterization of the internal individual chemical environment is expected to enhance understanding of the environmental threats to health., Objectives: We developed and applied a harmonized protocol to collect comparable human biomonitoring data all over Europe., Methods: In 17 European countries, we measured mercury in hair and cotinine, phthalate metabolites, and cadmium in urine of 1,844 children (5-11 years of age) and their mothers. Specimens were collected over a 5-month period in 2011-2012. We obtained information on personal characteristics, environment, and lifestyle. We used the resulting database to compare concentrations of exposure biomarkers within Europe, to identify determinants of exposure, and to compare exposure biomarkers with health-based guidelines., Results: Biomarker concentrations showed a wide variability in the European population. However, levels in children and mothers were highly correlated. Most biomarker concentrations were below the health-based guidance values., Conclusions: We have taken the first steps to assess personal chemical exposures in Europe as a whole. Key success factors were the harmonized protocol development, intensive training and capacity building for field work, chemical analysis and communication, as well as stringent quality control programs for chemical and data analysis. Our project demonstrates the feasibility of a Europe-wide human biomonitoring framework to support the decision-making process of environmental measures to protect public health.