Effect of Neurotoxin Exposure on Blood Biomarkers of Neurodegeneration and Alzheimer Disease.

AIM: To determine whether exposure to neurotoxins in midlife is associated with changes in blood-based biomarkers of neurodegeneration and Alzheimer disease pathology. METHODS: Blood cadmium, lead, neurofilament light (NfL) chain, total tau (TTau), and amyloid beta (Aß) 40 and Aß42 concentrations were measured in 1516 participants in the Beaver Dam Offspring Study. Linear mixed-effect models were used to determine associations between baseline cadmium and lead levels and baseline NfL, TTau, and Aß42/Aß40, and 10-year change in concentrations using repeated measures of these biomarkers as the outcome. RESULTS: In women, higher cadmium and lead levels were associated with higher baseline TTau concentrations. A higher baseline cadmium level was associated with lower baseline Aß42/Aß40 in both men and women. In age-sex-adjusted models, a doubling in baseline cadmium level was associated with a 0.2% (95% CI: 0.0, 0.3) higher increase per year in NfL concentrations. In men, a doubling of baseline lead level was associated with a 0.9% (95% CI: 0.1, 1.7) higher increase per year in TTau concentration. CONCLUSIONS: Participants with relatively higher levels of cadmium and lead had blood biomarker concentrations consistent with more neuronal damage and Alzheimer disease pathology. Environmental exposure to neurotoxins may contribute to neurodegeneration.

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.

The pupil constriction to light is associated with cognitive measures in middle-aged and older adults.

AIMS: The evidence relating the pupil light reflex (PLR) and cognition have been inconsistent. In this cross-sectional study, we evaluated the association between the PLR and cognition in community-dwelling middle-aged and older individuals. METHODS: Pupil reactivity was recorded in a subgroup of 403 participants (mean age 60.7 years, 57.3% females) in an epidemiologic study of aging. Ten pupil parameters were calculated to describe pupil constriction to light stimuli. A principal component analysis (PCA) score was used to calculate an overall performance over four cognitive testings. Linear regression was used to assess the association between pupil parameters and PCA scores, adjusting for age, sex, education, medications, health-related quality of life questionnaire, and systemic and ocular comorbidities. RESULTS: The PCA scores decreased by 0.039 [95% CI (- 0.050, - 0.028)] per year increase in age and were lower in males than females by 0.76 [95% CI (- 0.96, - 0.55)] (p < 0.001). Pupil constriction amplitude in millimeters and the duration from stimulus onset to maximal constriction velocity were significantly associated with cognition after adjusting for (1) age and sex and (2) age, sex, and multiple covariates (p < 0.05). CONCLUSIONS: In this study, we provided moderate evidence suggesting the association between PLR and neuropsychological cognitive measures. The findings suggest the potential of pupil reactivity to serve as a biomarker of brain aging and warrant further longitudinal study to assess if changes in the PLR can predict cognitive decline over time.

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.

Relationship Between Diet, Tinnitus, and Hearing Difficulties.

OBJECTIVES: Diet may affect susceptibility of the inner ear to noise and age-related effects that lead to tinnitus and hearing loss. This study used complementary single nutrient and dietary pattern analysis based on statistical grouping of usual dietary intake in a cross-sectional analysis of tinnitus and hearing difficulties in a large population study sample. DESIGN: The research was conducted using the UK Biobank resource. Tinnitus was based on report of ringing or buzzing in one or both ears that lasts more than five minutes at a time and is currently experienced at least some of the time. Identification of a hearing problem was based on self-reported difficulties with hearing. Usual dietary intake and dietary patterns (involving statistical grouping of intake to account for how foods are combined in real-life diets) were estimated based on between two and five administrations of the Oxford Web-Q 24-hour dietary recall questionnaire over the course of a year for 34,576 UK adult participants aged 40 to 69. RESULTS: In a multivariate model, higher intake of vitamin B12 was associated with reduced odds of tinnitus, while higher intakes of calcium, iron, and fat were associated with increased odds (B12, odds ratio [OR] 0.85, 95% confidence interval [CI] 0.75 to 0.97; Calcium, OR 1.20, 95% CI 1.08 to 1.34; Iron, OR 1.20, 95% CI 1.05 to 1.37; Fat, OR 1.33, 95% CI 1.09 to 1.62, respectively, for quintile 5 versus quintile 1). A dietary pattern characterised by high protein intake was associated with reduced odds of tinnitus (OR 0.90, 95% CI 0.82 to 0.99 for quintile 5 versus quintile 1). Higher vitamin D intake was associated with reduced odds of hearing difficulties (OR 0.90, 95% CI 0.81 to 1.00 for quintile 5 versus quintile 1), as were dietary patterns high in fruit and vegetables and meat and low in fat (Prudent diet: OR 0.89, 95% CI 0.83 to 0.96; High protein: OR 0.88, 95% CI 0.82 to 0.95; High fat: OR 1.16, 95% CI 1.08 to 1.24, respectively, for quintile 5 versus quintile 1). CONCLUSIONS: There were associations between both single nutrients and dietary patterns with tinnitus and hearing difficulties. Although the size of the associations was small, universal exposure for dietary factors indicates that there may be a substantial impact of diet on levels of tinnitus and hearing difficulties in the population. This study showed that dietary factors might be important for hearing health.

Oxidized Low-density Lipoprotein and the Incidence of Age-related Macular Degeneration.

PURPOSE: To examine the relationship between serum oxidized low-density lipoprotein (ox-LDL) cholesterol and the incidence of age-related macular degeneration (AMD) over a 25-year period in a sample of persons from the population-based Beaver Dam Eye Study (BDES). DESIGN: Observational prospective cohort study. PARTICIPANTS: A total of 4972 people from the BDES (aged 43-84 years and living in Beaver Dam, Wisconsin in 1988) seen during at least 1 of 6 examination phases at approximately 5-year intervals between 1988 and 2016. METHODS: A 50% random sample of participants (N = 2468) was selected for ox-LDL measurements. Stored frozen specimens from every examination phase were processed using an enzyme-linked immunosorbent assay from a single batch. All available intervals were included for a person, resulting in 6586 person-visits. MAIN OUTCOME MEASURES: Age-related macular degeneration was assessed using the Wisconsin Age-related Maculopathy Grading System, and severity was defined using a 5-step severity scale. The severity of the worse eye at each examination was used for analyses. A multi-state Markov (MSM) model was fit to simultaneously assess the ox-LDL relationship to all AMD transitions, including incidence of any AMD, incidence of late AMD, and worsening and improvement of AMD over the 25 years of the study. RESULTS: The mean (standard deviation) level of ox-LDL was 75.3 (23.1) U/L at the baseline examination. When adjusting for age, sex, ARMS2 and CFH risk alleles, and examination phase, the ox-LDL at the beginning of a period was not statistically significantly associated with the incidence of any AMD (hazard ratio per 10 U/L ox-LDL was 1.03, 95% confidence interval 0.98,1.09). Furthermore, ox-LDL was not associated with worsening anywhere along the AMD severity scale, nor with incidence of late AMD. The lack of relationships of ox-LDL to the incidence of any AMD or worsening of AMD remained after adjustment for history of statin use, smoking status, body mass index, and history of cardiovascular disease (data not shown). CONCLUSIONS: Our findings do not provide evidence for statistically significant relationships between ox-LDL and AMD disease development or worsening of AMD.

RISK FACTORS FOR HEARING IMPAIRMENT IN TYPE 1 DIABETES.

Objective: Studies have demonstrated that glycated hemoglobin (HbA1c) is a significant predictor of hearing impairment in type 1 diabetes. We identified additional factors associated with hearing impairment in participants with type 1 diabetes from the Diabetes Control and Complications Trial and its observational follow-up, the Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Methods: A total of 1,150 DCCT/EDIC participants were recruited for the Hearing Study. A medical history, physical measurements, and a self-administered hearing questionnaire were obtained. Audiometry was performed by study-certified personnel and assessed centrally. Logistic regression models assessed the association of risk factors and comorbidities with speech- and high-frequency hearing impairment. Results: Mean age was 55 ± 7 years, duration of diabetes 34 ± 5 years, and DCCT/EDIC HbA1c 7.9 ± 0.9% (63 mmol/mol). In multivariable models, higher odds of speech-frequency impairment were significantly associated with older age, higher HbA1c, history of noise exposure, male sex, and higher triglycerides. Higher odds of high-frequency impairment were associated with older age, male sex, history of noise exposure, higher skin intrinsic florescence (SIF) as a marker of tissue glycation, higher HbA1c, nonprofessional/nontechnical occupations, sedentary activity, and lower low-density-lipoprotein cholesterol. Among participants who previously completed computed tomography and carotid ultrasonography, coronary artery calcification (CAC) >0 and carotid intima-medial thickness were significantly associated with high-but not speech-frequency impairment. Conclusion: Consistent with previous reports, male sex, age, several metabolic factors, and noise exposure are independently associated with hearing impairment. The association with SIF further emphasizes the importance of glycemia-as a modifiable risk factor-over time. In addition, the macrovascular contribution of CAC is novel and important. Abbreviations: AER = albumin excretion rate; CAC = coronary artery calcification; CVD = cardiovascular disease; DCCT/EDIC = Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications; eGFR = estimated glomerular filtration rate; ETDRS = Early Treatment Diabetic Retinopathy Study; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; IMT = intima-media thickness; LDL = low-density lipoprotein; NHANES = National Health and Nutrition Examination Survey; OR = odds ratio; SIF = skin intrinsic fluorescence; T1D = type 1 diabetes.

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.

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.

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.

At the interface of sensory and motor dysfunctions and Alzheimer's disease.

Recent evidence indicates that sensory and motor changes may precede the cognitive symptoms of Alzheimer's disease (AD) by several years and may signify increased risk of developing AD. Traditionally, sensory and motor dysfunctions in aging and AD have been studied separately. To ascertain the evidence supporting the relationship between age-related changes in sensory and motor systems and the development of AD and to facilitate communication between several disciplines, the National Institute on Aging held an exploratory workshop titled "Sensory and Motor Dysfunctions in Aging and AD." The scientific sessions of the workshop focused on age-related and neuropathologic changes in the olfactory, visual, auditory, and motor systems, followed by extensive discussion and hypothesis generation related to the possible links among sensory, cognitive, and motor domains in aging and AD. Based on the data presented and discussed at this workshop, it is clear that sensory and motor regions of the central nervous system are affected by AD pathology and that interventions targeting amelioration of sensory-motor deficits in AD may enhance patient function as AD progresses.

Pulse wave velocity and cognitive function in older adults.

Arterial stiffness may be associated with cognitive function. In this study, pulse wave velocity (PWV) was measured from the carotid to femoral (CF-PWV) and from the carotid to radial (CR-PWV) with the Complior SP System. Cognitive function was measured by 6 tests of executive function, psychomotor speed, memory, and language fluency. A total of 1433 participants were included (mean age 75 y, 43% men). Adjusting for age, sex, education, pulse rate, hemoglobin A1C, high-density lipoprotein cholesterol, hypertension, cardiovascular disease history, smoking, drinking, and depression symptoms, a CF-PWV>12 m/s was associated with a lower Mini-Mental State Examination score (coefficient: -0.31, SE: 0.11, P=0.005), fewer words recalled on Auditory Verbal Learning Test (coefficient: -1.10, SE: 0.43, P=0.01), and lower score on the composite cognition score (coefficient: -0.10, SE: 0.05, P=0.04) and marginally significantly associated with longer time to complete Trail Making Test-part B (coefficient: 6.30, SE: 3.41, P=0.06), CF-PWV was not associated with Trail Making Test-part A, Digit Symbol Substation Test, or Verbal Fluency Test. No associations were found between CR-PWV and cognitive performance measures. Higher large artery stiffness was associated with worse cognitive function, and longitudinal studies are needed to confirm these associations.

Vision impairment and dual sensory problems in middle age.

PURPOSE: Vision and hearing impairments are known to increase in middle age. In this study we describe the prevalence of vision impairment and dual sensory impairment in UK adults aged 40-69 years in a very large and recently ascertained data set. The associations between vision impairment, age, sex, socioeconomic status, and ethnicity are reported. METHODS: This research was conducted using the UK Biobank Resource, with subsets of UK Biobank data analysed with respect to self-report of eye problems and glasses use. Better-eye visual acuity with habitually worn refractive correction was assessed with a logMAR chart (n = 116,682). Better-ear speech reception threshold was measured with an adaptive speech in noise test, the Digit Triplet Test (n = 164,770). Prevalence estimates were weighted with respect to UK 2001 Census data. RESULTS: Prevalence of mild visual impairment (VA >0.1 logMAR (6/7.5, 20/25) and ≥0.48 (6/18, 20/60)) and low vision (VA >0.48 (6/18, 20/60) and ≥1.3 (6/120, 20/400)) was estimated at 13.1% (95% CI 12.9-13.4) and 0.8% (95% CI 0.7-0.9), respectively. Use of glasses was 88.0% (95% CI 87.9-88.1). The prevalence of dual sensory impairment was 3.1% (95% CI 3.0-3.2) and there was a nine-fold increase in the prevalence of dual sensory problems between the youngest and oldest age groups. Older adults, those from low socioeconomic and ethnic minority backgrounds were most at risk for vision problems. CONCLUSIONS: Mild vision impairment is common in middle aged UK adults, despite widespread use of spectacles. Increased likelihood of vision impairment with older age and with ethnic minorities is of concern given ageing and more ethnically diverse populations. Possible barriers to optometric care for those from low socioeconomic and ethnic minority backgrounds may require attention. A higher than expected prevalence of dual impairment suggests that hearing and vision problems share common causes. Optometrists should consider screening for hearing problems, particularly among older adults.

The relationship of atherosclerosis to the 10-year cumulative incidence of age-related macular degeneration: the Beaver Dam studies.

OBJECTIVE: To describe the relationships of intima-media thickness (IMT), plaque in the carotid artery, angina, myocardial infarction (MI), and stroke to the 10-year cumulative incidence of early and late age-related macular degeneration (AMD) and progression of AMD. DESIGN: Cohort study. PARTICIPANTS: A total of 1700 persons aged 53 to 96 years who participated in both the Epidemiology of Hearing Loss Study and the Beaver Dam Eye Study in 1998-2000, with photographs gradable for AMD at 5-year (2003-2005) and 10-year (2008-2010) follow-up examinations. METHODS: The IMT and presence of plaque were assessed using B-mode ultrasonography of the carotid artery. Presence of angina, MI, and stroke were defined on the basis of a self-reported history of physician diagnosis. The presence and severity of AMD were determined by systematic grading of stereoscopic color fundus photographs. MAIN OUTCOME MEASURES: Age-related macular degeneration. RESULTS: The 10-year cumulative incidence of early AMD was 15.7%, and the 10-year cumulative incidence of late AMD was 4.0%. After adjusting for age, sex, body mass index, smoking status, age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) genotypes, and other factors, mean IMT was associated with the 10-year incidence of early AMD (odds ratio [OR] per 0.1 mm IMT, 1.11; 95% confidence interval [CI], 1.00-1.21; P = 0.03) and late AMD (OR per 0.1 mm IMT, 1.27; CI, 1.10-1.47; P = 0.001). Mean IMT was associated with the 10-year incidence of pure geographic atrophy (OR per 0.1 mm IMT, 1.31; CI, 1.05-1.64; P = 0.02) but not exudative AMD (OR per 0.1 mm IMT, 1.14; CI, 0.97-1.34; P = 0.11). Similar associations were found for maximum IMT. The number of sites with plaque was related to the incidence of late AMD (OR per 0.1 mm IMT, 2.79 for 4-6 sites vs. none; CI, 1.06-7.37; P = 0.04) but not to early AMD. A history of angina, MI, or stroke was not related to any incident AMD outcome. CONCLUSIONS: In these population-based data, carotid artery IMT and carotid plaques had a weak relationship to the incidence of late AMD that was independent of systemic and genetic risk factors. Angina, MI, and stroke were not related to AMD. It is unclear whether the carotid IMT is a risk indicator of processes affecting Bruch's membrane and the retinal pigment epithelium, or a measure of atherosclerosis affecting susceptibility to AMD. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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.