Inflammation, metabolic dysregulation and environmental neurotoxins and risk of cognitive decline and impairment in midlife.

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-1Tertile(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 (RRT3 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 103/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.

Factors Associated with the Macular Ganglion Cell-Inner Plexiform Layer Thickness in a Cohort of Middle-aged U.S. Adults.

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.

Predicting hearing aid use in adults: the Beaver Dam Offspring Study.

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.

Neuroprotective Biomarkers and Cognitive Function in a Long-Term Prospective Population-based Study of Aging US Adults.

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.

Invasive central venous monitoring during hepatic resection: unnecessary for most patients.

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.

Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci.

Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ~50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.

Dichotic Digits Test Performance Across the Ages: Results From Two Large Epidemiologic Cohort Studies.

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.

Prospective Randomized Controlled Trial of Liberal Vs Restricted Perioperative Fluid Management in Patients Undergoing Pancreatectomy.

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.

NSAID Use and Incident Cognitive Impairment in a Population-based Cohort.

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.

Loci influencing blood pressure identified using a cardiovascular gene-centric array.

Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped ∼50 000 single-nucleotide polymorphisms (SNPs) that capture variation in ∼2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P < 2.4 × 10(-6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.

Self-Reported Hearing Difficulties Among Adults With Normal Audiograms: The Beaver Dam Offspring Study.

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.

Inflammatory and vascular markers and olfactory impairment in older adults.

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.

Hearing-aid use and long-term health outcomes: Hearing handicap, mental health, social engagement, cognitive function, physical health, and mortality.

OBJECTIVE: To clarify the impact of hearing aids on mental health, social engagement, cognitive function, and physical health outcomes in older adults with hearing impairment. DESIGN: We assessed hearing handicap (hearing handicap inventory for the elderly; HHIE-S), cognition (mini mental state exam, trail making, auditory verbal learning, digit-symbol substitution, verbal fluency, incidence of cognitive impairment), physical health (SF-12 physical component, basic and instrumental activities of daily living, mortality), social engagement (hours per week spent in solitary activities), and mental health (SF-12 mental component) at baseline, five years prior to baseline, and five and 11 years after baseline. STUDY SAMPLE: Community-dwelling older adults with hearing impairment (N = 666) from the epidemiology of hearing loss study cohort. RESULTS: There were no significant differences between hearing-aid users and non-users in cognitive, social engagement, or mental health outcomes at any time point. Aided HHIE-S was significantly better than unaided HHIE-S. At 11 years hearing-aid users had significantly better SF-12 physical health scores (46.2 versus 41.2; p = 0.03). There was no difference in incidence of cognitive impairment or mortality. CONCLUSION: There was no evidence that hearing aids promote cognitive function, mental health, or social engagement. Hearing aids may reduce hearing handicap and promote better physical health.

Factors related to fungiform papillae density: the beaver dam offspring study.

The distribution of fungiform papillae density and associated factors were examined in the Beaver Dam Offspring Study. Data were from 2371 participants (mean age = 48.8 years, range = 21-84 years) with 1108 males and 1263 females. Fungiform papillae were highlighted with blue food coloring and the number of fungiform papillae within a standard 6-mm circle was counted. Whole mouth suprathreshold taste intensity was measured. The mean fungiform papillae density was 103.5 papillae/cm(2) (range = 0-212.2 papillae/cm(2)). For each 5-year increase in age, the mean fungiform papillae density was 2.8 papillae/cm(2) lower and the mean density for males was 10.2 papillae/cm(2) lower than for females. Smokers had significantly lower mean densities (former smokers: -5.1 papillae/cm(2); current smokers: -9.3 papillae/cm(2)) than nonsmokers, and heavy alcohol drinkers had a mean density that was 4.7 papillae/cm(2) lower than nonheavy drinkers. Solvent exposure was related to a significantly higher density (+6.8 papillae/cm(2)). The heritability estimate for fungiform papillae density was 40.2%. Propylthiouracil taster status, TAS2R38 haplotype, and perceived taste intensity were not related to density. In summary, wide variability in fungiform papillae density was observed and a number of related factors were found including the modifiable factors of smoking and alcohol consumption.

Changes in environmental tobacco smoke exposure: the Beaver Dam experience.

OBJECTIVES: Environmental tobacco smoke (ETS) exposure has been associated with adverse health outcomes. Our goal was to determine if ETS exposure changed between 1998-2000 and 2003-2005 among participants in the population-based Epidemiology of Hearing Loss Study. METHODS: ETS exposure was ascertained using a cotinine-validated questionnaire at the 5-year (1998-2000) and 10-year follow-up examinations (2003-2005). Non-smoking participants with data from both visits were included (n=1898; ages 53-96 years at 5-yr follow-up). McNemar's test was used to test differences in ETS exposure overall and in 3 settings: home, work, and social settings. Generalized estimating equations (GEE) were used for multivariate logistic regression models of exposure. RESULTS: The proportion of nonsmokers with no or little ETS exposure increased from 80% to 88% (P< 0.0001). The percent living in a home with no indoor smokers increased from 94% to 97% (P<0.0001). The percent reporting no exposure at work increased from 91% to 95% (P<0.0001). The percent reporting the lowest frequency of social exposure increased from 65% to 77% (P<0.0001). In the GEE model, age was inversely associated with overall ETS exposure (Odds Ratio [OR] per 5 yr= 0.87, 95% CI= 0.81, 0.94), as was education (OR for college vs < high school=0.25, 95% CI=0.16, 0.37), female gender (ORI= 0.41, 95% CI= 0.33, 0.51), and later examination period (OR =0.62, 95% CI= 0.53, 0.73); current employment was positively associated with exposure (OR=1.44, 95% CI=1.14, 1.83). CONCLUSIONS: Between the late 1990s and the mid-2000s, ETS exposure in older adults decreased. Decreasing exposures suggest there may be future declines in ETS-related adverse health outcomes.

Lifestyle and factors of vascular and metabolic health and inflammation are associated with sensorineural-neurocognitive aging in older adults.

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.

Associations of Hearing Loss and Hearing Aid Use With Cognition, Health-Related Quality of Life, and Depressive Symptoms.

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.

Olfactory impairment in an adult population: the Beaver Dam Offspring Study.

The objective of this study was to determine the prevalence of olfactory impairment and associated risk factors and the effects of olfactory impairment on dietary choices and quality of life. Odor identification was measured in 2838 participants aged 21-84 years (mean 49 years) in the Beaver Dam Offspring Study. The overall prevalence of olfactory impairment was 3.8%, increased with age (from 0.6% in those<35 years to 13.9% among those≥65 years) and was more common in men than women. In a multivariate model age (odds ratio [OR]=1.48, 95% confidence interval [CI]=1.33, 1.64 for every 5-year increase), nasal polyps or deviated septum (OR=2.69, 95% CI=1.62, 4.48), ankle-brachial index<0.9 (OR=3.62, 95% CI=1.45, 9.01), and smoking (women only) (OR=2.43, 95% CI=1.19, 4.98 ever smoked vs. never) were associated with an increased odds of olfactory impairment, whereas higher household income, ≥$50,000 versus <$50,000 per year, was associated with a decreased odds of olfactory impairment (OR=0.48, 95% CI=0.31, 0.73). Participants with olfactory impairment were less likely to report that food tasted as good as it used to, or that they experienced food flavors the same. There was no association between olfactory impairment and general health-related quality of life, depressive symptoms, or dietary choices. The prevalence of olfactory impairment was low in this largely middle-aged cohort, and some factors associated with olfactory impairment are potentially modifiable.

The Association of Psychological Well-Being With Sensory and Cognitive Function and Neuronal Health in Aging Adults.

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.

Determinants of hearing aid acquisition in older adults.

OBJECTIVES: We determined factors associated with hearing aid acquisition in older adults. METHODS: We conducted a population-based, prospective study that used information from 3 examinations performed on study participants as part of the Epidemiology of Hearing Loss Study (1993-2005). We included participants (n = 718; mean age = 70.5 years) who exhibited hearing loss at baseline or the first follow-up and had no prior history of hearing aid use. We defined hearing loss as a pure tone threshold average (PTA) at 0.5, 1, 2, and 4 kilohertz in the better ear of greater than 25 decibels Hearing Level. RESULTS: The 10-year cumulative incidence of hearing aid acquisition was 35.7%. Associated factors included education (college graduate vs all others: hazard ratio [HR] = 2.5; 95% confidence interval [CI] = 1.5, 4.1), self-perception of hearing (poor vs good or better: HR = 2.5; 95% CI = 1.3, 5.0), score on a perceived hearing handicap inventory (+1 difference: HR = 1.1; 95% CI = 1.0, 1.1), and PTA (+ 5 dB difference: HR = 1.4; 95% CI = 1.2, 1.6). CONCLUSIONS: The low rate of hearing aid ownership among older adults is a problem that still needs to be addressed.