Dual Sensory Impairment in Older Adults Increases the Risk of Mortality: A Population-Based Study

Although concurrent vision and hearing loss are common in older adults, population-based data on their relationship with mortality is limited. This cohort study investigated the association between objectively measured dual sensory impairment (DSI) with mortality risk over 10 years. 2812 Blue Mountains Eye Study participants aged 55 years and older at baseline were included for analyses. Visual impairment was defined as visual acuity less than 20/40 (better eye), and hearing impairment as average pure-tone air conduction threshold greater than 25 dB HL (500–4000 Hz, better ear). Ten-year all-cause mortality was confirmed using the Australian National Death Index. After ten years, 64% and 11% of participants with DSI and no sensory loss, respectively, had died. After multivariable adjustment, participants with DSI (presenting visual impairment and hearing impairment) compared to those with no sensory impairment at baseline, had 62% increased risk of all-cause mortality, hazard ratio, HR, 1.62 (95% confidence intervals, CI, 1.16–2.26). This association was more marked in those with both moderate-severe hearing loss (>40 dB HL) and presenting visual impairment, HR 1.84 (95% CI 1.19–2.86). Participants with either presenting visual impairment only or hearing impairment only, did not have an increased risk of mortality, HR 1.05 (95% CI 0.61–1.80) and HR 1.24 (95% CI 0.99–1.54), respectively. Concurrent best-corrected visual impairment and moderate-severe hearing loss was more strongly associated with mortality 10 years later, HR 2.19 (95% CI 1.20–4.03). Objectively measured DSI was an independent predictor of total mortality in older adults. DSI was associated with a risk of death greater than that of either vision loss only or hearing loss alone.     

Visual Impairment,Hearing Loss and Cognitive Function in an Older Population: Longitudinal Findings from the Blue Mountains Eye Study

The presence of visual impairment (VI) and hearing loss (HL) with may be a marker for subsequent cognitive decline over time in older people. A prospective, longitudinal population-based study of the 3654 participants of the Blue Mountains Eye Study were assessed for the associations between VI and HL and a decline in mini-mental state examination (MMSE) scores over a duration of 10 years from the 5-year (baseline of this report) to the 15-year follow-up visits. MMSE was assessed at the 5-, 10- and 15-year follow-up visits. A decline ≥3 scores from 5-year to 10- or 15-year visits indicated possible cognitive decline. VI was defined as best-corrected visual acuity <6/12 in the worse-eye, HL was defined as pure-tone average >40 decibels in the worse-ear and dual sensory impairment (DSI) was defined by the co-presence of VI and HL, detected at 5-year follow-up (baseline of this report). Participants with no VI and HL over the same 5- or 10-year corresponding period were controls. Associations of VI, HL and DSI with possible cognitive decline were assessed using logistic regression models adjusting for age and sex after excluding subjects with a stroke history. The presence of VI, HL or DSI was not associated with possible cognitive decline over 5 years (odds ratio (OR) 0.84, 95% confidence-intervals (CI) 0.40–1.79, OR 1.02, 95% CI 0.61–1.70 and 1.41, 95% CI 0.54–3.72, respectively) or 10 years (OR 1.09, 95% CI 0.52–2.30, OR 1.09, 95% CI 0.65–1.82 and 1.15, 95% CI 0.28–4.73, respectively). There were no changes to these findings after adjustment for other potential confounders. Age was significantly associated with possible cognitive decline (OR 1.07, 95% CI 1.04–1.10 for both periods). Neither visual impairment, hearing loss nor dual sensory impairment was independently associated with subsequent decline in cognition.     

Association of Hearing Loss and Tinnitus with Health-Related Quality of Life: The Korea National Health and Nutrition Examination Survey

Background

Hearing loss and tinnitus are global public health concerns. There have been some studies suggesting a relationship between hearing loss and tinnitus and impaired health-related quality of life (HRQoL), but there have been no large cross-sectional epidemiologic studies of a representative sample of the entire country population investigating this possible association.

Objective

The aim of this study was to investigate the relationship between hearing loss and tinnitus and HRQoL in South Korea using data from the Korea National Health and Nutrition Examination Surveys during 2010–2012.

Methods

Cross-sectional data of 11,266 adults who completed the Korea National Health and Nutrition Examination Surveys were analyzed. Subjects were divided into four groups as follows: normal hearing without tinnitus, normal hearing with tinnitus, hearing loss without tinnitus, and hearing loss with tinnitus.

Results

Among the population that was ≥19 years of age, the prevalence of unilateral hearing loss was 9.69% and that of tinnitus in the prior 12 months was 32.76%. The hearing loss with tinnitus group had the highest percentage of subjects who responded “some or extreme problems” in all five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) of HRQoL. After adjustment for age, gender, body mass index, smoking status, alcohol intake, regular exercise, house income, education level, diabetes, hypertension, and stress level, the HRQoL odds ratios (OR) were 1.47 (95% confidence interval [CI], 1.07–2.02) for mobility, 1.59 (95% CI, 1.07–2.37) for usual activity, and 1.84 (95% CI, 1.25–2.70) for anxiety/depression in the hearing loss with tinnitus group, compared with the normal hearing without tinnitus group. The ORs for the normal hearing with tinnitus group compared with the hearing loss without tinnitus group was increased in all five dimensions of HRQoL after adjustment for confounders.

Conclusion

Hearing loss with tinnitus has a considerable impact on HRQoL in the Korean population. In our study, the hearing loss without tinnitus group showed better a HRQoL than the normal hearing with tinnitus group.     

Association of GRM7 Variants with Different Phenotype Patterns of Age-Related Hearing Impairment in an Elderly Male Han Chinese Population

Several single nucleotide polymorphisms (SNPs) of the Glutamate metabotrophic receptor 7 gene (GRM7) have recently been identified by the genome-wide association study (GWAS) as potentially playing a role in susceptibility to age-related hearing impairment (ARHI), however this has not been validated in the Han Chinese population. The aim of this study was to determine if these SNPs are also associated with ARHI in an elderly male Han Chinese population. In this case-control candidate genes association study, a total of 982 men with ARHI and 324 normal-hearing controls subjects were studied. Using K-means cluster analysis, four audiogram shape subtypes of ARHI were identified in the case group: ‘‘flat shape (FL)’’, ‘‘sloping shape (SL)’’, ‘‘2-4 kHz abrupt loss (AL) shape’’ and ‘‘8 kHz dip (8D) shape’’. Results suggested that the SNP rs11928865 (A>T) of GRM7 was significantly associated with ARHI after adjusting for non-genetic factors (p= 0.000472, OR= 1.599, 95%CI= 1.229~2.081). Furthermore, frequency of TT genotype (rs11928865) were significant higher in the SL subgroup and AL subgroup with compared to controls group (p= 9.41E-05, OR= 1.945, 95%CI= 1.393~2.715; p= 0.000109, OR= 1.915, 95%CI= 1.378~2.661 adjusted, respectively) after Bonferroni correction. However, there wasn’t significant difference in the frequency of the TT genotype between cases in the FL subgroup or the 8D subgroup with when compared with controls. Results of the current study suggest that, in an elderly male Han Chinese population, GRM7 SNP rs11928865 (TT) occurs more frequently in ARHI patients with SL and AL phenotype patterns.     

Components of Metabolic Syndrome as Risk Factors for Hearing Threshold Shifts

Background

Hearing loss was a common, chronically disabling condition in the general population and had been associated with several inflammatory diseases. Metabolic syndrome, which was associated with insulin resistance and visceral obesity, was considered a chronic inflammatory disease. To date, few attempts had been made to establish a direct relationship between hearing loss and metabolic syndrome. The aim of the present study was to investigate the relationship between metabolic syndrome and hearing loss by analyzing the data in the reports of the National Health and Nutrition Examination Survey 1999–2004.

Methods

This study included 2100 participants aged ≤ 65 years who enrolled in the National Health and Nutrition Examination Survey (1999–2004). We examined the relationship between the presence of different features of metabolic syndrome in the participants and their pure-tone air-conduction hearing thresholds, including low-frequency and high-frequency thresholds.

Results

After adjusting for potential confounders, such as age, medical conditions, and smoking status, the participants with more components of metabolic syndrome were found to have higher hearing thresholds than those with fewer components of metabolic syndrome (p < 0.05 for a trend). The low-frequency hearing threshold was associated with individual components of metabolic syndrome, such as abdominal obesity, high blood pressure, elevated triglycerides, and a low level of high-density lipoprotein cholesterol (HDL-C) (p < 0.05 for all parameters).

Conclusions

The results indicated that the presence of a greater number of components of metabolic syndrome was significantly associated with the hearing threshold in the US adult population. Among the components of metabolic syndrome, the most apparent association was observed between low HDL and hearing loss.     

Age- and Gender-Related Mean Hearing Threshold in a Highly-Screened Population: The Korean National Health and Nutrition Examination Survey 2010–2012

Background

In evaluating hearing disability in medicolegal work, the apportionment of age- and gender-related sensorineural hearing loss should be considered as a prior factor, especially for the elderly. However, in the literature written in the English language no studies have reported on the age- and gender-related mean hearing threshold for the South Korean population.

Objective

This study aimed to identify the mean hearing thresholds in the South Korean population to establish reference data and to identify the age- and gender-related characteristics.

Methods

This study is based on the Korea National Health and Nutrition Examination Survey (KNHANES) 2010–2012, which was conducted by the Korean government, the data of which was disclosed to the public. A total of 15,606 participants (unweighted) representing 33,011,778 Koreans (weighted) with normal tympanic membrane and no history of regular or occupational noise exposure were selected and analyzed in this study. The relationship between the hearing threshold level and frequency, age, and gender was investigated and analyzed in a highly-screened population by considering the sample weights of a complex survey design.

Results

A gender ratio difference was found between the unweighted and the weighted designs: male:female, 41.0%: 59.0% (unweighted, participants) vs. 47.2%:52.8% (weighted, representing population). As age increased, the hearing threshold increased for all frequencies. Hearing thresholds of 3 kHz, 4 kHz, and 6 kHz showed a statistical difference between both genders for people older than 30, with the 4 kHz frequency showing the largest difference. This paper presents details about the mean hearing threshold based on age and gender.

Conclusions

The data from KNHANES 2010–2012 showed gender differences at hearing thresholds of 3 kHz, 4 kHz, and 6 kHz in a highly-screened population. The most significant gender difference in relation to hearing threshold was observed at 4 kHz. The hearing thresholds at all of the tested frequencies worsened with increasing age. The mean hearing thresholds suggested in this study will be useful for the formulation of healthcare-related hearing policies and used as reference data for disability ratings for hearing loss due to various causes.     

A systematic review of studies measuring and reporting hearing aid usage in older adults since 1999: a descriptive summary of measurement tools

Objective

A systematic review was conducted to identify and quality assess how studies published since 1999 have measured and reported the usage of hearing aids in older adults. The relationship between usage and other dimensions of hearing aid outcome, age and hearing loss are summarised.

Data sources

Articles were identified through systematic searches in PubMed/MEDLINE, The University of Nottingham Online Catalogue, Web of Science and through reference checking. Study eligibility criteria: (1) participants aged fifty years or over with sensori-neural hearing loss, (2) provision of an air conduction hearing aid, (3) inclusion of hearing aid usage measure(s) and (4) published between 1999 and 2011.

Results

Of the initial 1933 papers obtained from the searches, a total of 64 were found eligible for review and were quality assessed on six dimensions: study design, choice of outcome instruments, level of reporting (usage, age, and audiometry) and cross validation of usage measures. Five papers were rated as being of high quality (scoring 10–12), 35 papers were rated as being of moderate quality (scoring 7–9), 22 as low quality (scoring 4–6) and two as very low quality (scoring 0–2). Fifteen different methods were identified for assessing the usage of hearing aids.

Conclusions

Generally, the usage data reviewed was not well specified. There was a lack of consistency and robustness in the way that usage of hearing aids was assessed and categorised. There is a need for more standardised level of reporting of hearing aid usage data to further understand the relationship between usage and hearing aid outcomes.     

Relation of Pulse Pressure to Long-Distance Gait Speed in Community-Dwelling Older Adults: Findings from the LIFE-P Study

Background

Reduced gait speed is associated with falls, late-life disability, hospitalization/institutionalization and cardiovascular morbidity and mortality. Aging is also accompanied by a widening of pulse pressure (PP) that contributes to ventricular-vascular uncoupling. The purpose of this study was to test the hypothesis that PP is associated with long-distance gait speed in community-dwelling older adults in the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study.

Methods

Brachial blood pressure and 400-meter gait speed (average speed maintained over a 400-meter walk at “usual” pace) were assessed in 424 older adults between the ages of 70–89 yrs at risk for mobility disability (mean age = 77 yrs; 31% male). PP was calculated as systolic blood pressure (BP) – diastolic BP.

Results

Patients with a history of heart failure and stroke (n = 42) were excluded leaving 382 participants for final analysis. When categorized into tertiles of PP, participants within the highest PP tertile had significantly slower gait speed than those within the lowest PP tertile (p<0.05). Following stepwise multiple regression, PP was significantly and inversely associated with 400-meter gait speed (p<0.05). Other significant predictors of gait speed included: handgrip strength, body weight, age and history of diabetes mellitus (p<0.05). Mean arterial pressure, systolic BP and diastolic BP were not predictors of gait speed.

Conclusions

Pulse pressure is associated long-distance gait speed in community-dwelling older adults. Vascular senescence and altered ventricular-vascular coupling may be associated with the deterioration of mobility and physical function in older adults.     

Light Intensity Physical Activity and Sedentary Behavior in Relation to Body Mass Index and Grip Strength in Older Adults: Cross-Sectional Findings from the Lifestyle Interventions and Independence for Elders (LIFE) Study

BackgroundIdentifying modifiable determinants of fat mass and muscle strength in older adults is important given their impact on physical functioning and health. Light intensity physical activity and sedentary behavior are potential determinants, but their relations to these outcomes are poorly understood. We evaluated associations of light intensity physical activity and sedentary time—assessed both objectively and by self-report—with body mass index (BMI) and grip strength in a large sample of older adults.MethodsWe used cross-sectional baseline data from 1130 participants of the Lifestyle Interventions and Independence for Elders (LIFE) study, a community-dwelling sample of relatively sedentary older adults (70-89 years) at heightened risk of mobility disability. Time spent sedentary and in light intensity activity were assessed using an accelerometer worn for 3–7 days (Actigraph GT3X) and by self-report. Associations between these exposures and measured BMI and grip strength were evaluated using linear regression.ResultsGreater time spent in light intensity activity and lower sedentary times were both associated with lower BMI. This was evident using objective measures of lower-light intensity, and both objective and self-reported measures of higher-light intensity activity. Time spent watching television was positively associated with BMI, while reading and computer use were not. Greater time spent in higher but not lower intensities of light activity (assessed objectively) was associated with greater grip strength in men but not women, while neither objectively assessed nor self-reported sedentary time was associated with grip strength.ConclusionsIn this cross-sectional study, greater time spent in light intensity activity and lower sedentary times were associated with lower BMI. These results are consistent with the hypothesis that replacing sedentary activities with light intensity activities could lead to lower BMI levels and obesity prevalence among the population of older adults. However, longitudinal and experimental studies are needed to strengthen causal inferences.     

Association between Frailty,Osteoporosis, Falls and Hip Fractures among Community-Dwelling People Aged 50 Years and Older in Taiwan: Results from I-Lan Longitudinal Aging Study

Background

Association of frailty with adverse clinical outcomes has been reported in Western countries, but data from the Asian population are scarce. This study aimed to evaluate the epidemiology of frailty among community-dwelling middle-aged and elderly population and to explore its association with musculoskeletal health in Taiwan.

Methods

I-Lan Longitudinal Aging Study (ILAS) data were retrieved for this study. Frailty was defined by the Fried’s criteria; a comparison of demographic characteristics, physical performance, and body composition, including skeletal muscle mass and bone mineral density (BMD), as well as recent falls, history of hip fractures and the functional status of subjects with different frailty statuses were accomplished.

Results

Overall, the data of 1,839 participants (mean age: 63.9±9.3 years, male 47.5%) were obtained for analysis. The prevalence of pre-frailty was 42.3% in men and 38.8% in women, whereas the prevalence of frailty was 6.9% and 6.7% in men and women, respectively. Frailty was significantly associated with older age, the male gender, larger waist circumference, lower skeletal muscle index, lower hip BMD, poorer physical function, poorer nutritional status, and poorer cognitive function. Also, frailty was significantly associated with osteoporosis (OR: 7.73, 95% CI: 5.01–11.90, p<0.001), history of hip fractures (OR: 8.66, 95% CI: 2.47–30.40, p = 0.001), and recent falls (O.R: 2.53, 95% CI: 1.35–4.76, p = 0.004).

Conclusions

Frailty and pre-frailty, in Taiwan, was closely associated with recent falls, history of hip fractures and osteoporosis among community-dwelling people 50 years of age and older. Furthermore, frailty intervention programs should take an integrated approach towards strengthening both and muscle mass, as well as prevention of falls.     

Polymorphisms in the Mitochondrial DNA Control Region and Frailty in Older Adults

Background

Mitochondria contribute to the dynamics of cellular metabolism, the production of reactive oxygen species, and apoptotic pathways. Consequently, mitochondrial function has been hypothesized to influence functional decline and vulnerability to disease in later life. Mitochondrial genetic variation may contribute to altered susceptibility to the frailty syndrome in older adults.

Methodology/Principal Findings

To assess potential mitochondrial genetic contributions to the likelihood of frailty, mitochondrial DNA (mtDNA) variation was compared in frail and non-frail older adults. Associations of selected SNPs with a muscle strength phenotype were also explored. Participants were selected from the Cardiovascular Health Study (CHS), a population-based observational study (1989–1990, 1992–1993). At baseline, frailty was identified as the presence of three or more of five indicators (weakness, slowness, shrinking, low physical activity, and exhaustion). mtDNA variation was assessed in a pilot study, including 315 individuals selected as extremes of the frailty phenotype, using an oligonucleotide sequencing microarray based on the Revised Cambridge Reference Sequence. Three mtDNA SNPs were statistically significantly associated with frailty across all pilot participants or in sex-stratified comparisons: mt146, mt204, and mt228. In addition to pilot participants, 4,459 additional men and women with frailty classifications, and an overlapping subset of 4,453 individuals with grip strength measurements, were included in the study population genotyped at mt204 and mt228. In the study population, the mt204 C allele was associated with greater likelihood of frailty (adjusted odds ratio = 2.04, 95% CI = 1.07–3.60, p = 0.020) and lower grip strength (adjusted coefficient = −2.04, 95% CI = −3.33– −0.74, p = 0.002).

Conclusions

This study supports a role for mitochondrial genetic variation in the frailty syndrome and later life muscle strength, demonstrating the importance of the mitochondrial genome in complex geriatric phenotypes.     

Angiotensin 1–7 prevents the excessive force loss resulting from 14- and 28-day denervation in mouse EDL and soleus muscle

Denervation leads to muscle atrophy, which is described as muscle mass and force loss, the latter exceeding expectation from mass loss. The objective of this study was to determine the efficiency of angiotensin (Ang) 1–7 at reducing muscle atrophy in mouse extensor digitorum longus (EDL) and soleus following 14- and 28-d denervation periods. Some denervated mice were treated with Ang 1–7 or diminazene aceturate (DIZE), an ACE2 activator, to increase Ang 1–7 levels. Ang 1–7/DIZE treatment had little effect on muscle mass loss and fiber cross-sectional area reduction. Ang 1–7 and DIZE fully prevented the loss of tetanic force normalized to cross-sectional area and accentuated the increase in twitch force in denervated muscle. However, they did not prevent the shift of the force–frequency relationship toward lower stimulation frequencies. The Ang 1–7/DIZE effects on twitch and tetanic force were completely blocked by A779, a MasR antagonist, and were not observed in MasR^−/− muscles. Ang 1–7 reduced the extent of membrane depolarization, fully prevented the loss of membrane excitability, and maintained the action potential overshoot in denervated muscles. Ang 1–7 had no effect on the changes in α-actin, myosin, or MuRF-1, atrogin-1 protein content or the content of total or phosphorylated Akt, S6, and 4EPB. This is the first study that provides evidence that Ang 1–7 maintains normal muscle function in terms of maximum force and membrane excitability during 14- and 28-d periods after denervation.     

Eosinophil Inversely Associates with Type 2 Diabetes and Insulin Resistance in Chinese Adults

Context

Limited population-based study focused on relationship between eosinophil and type 2 diabetes (T2D).

Objectives

We aimed to evaluate the relationship between peripheral eosinophil percentage and glucose metabolism and insulin resistance in a large sample size of Chinese population aged 40 and older.

Design and Methods

A cross-sectional study was performed among 9,111 Chinese adults including 3,561 men and 5,550 women. The glucose metabolism status was confirmed by 75-g oral glucose tolerance test. Homeostasis model assessment of insulin resistance index and serum insulin levels were used to evaluate insulin resistance. Homeostasis model assessment-B was used to evaluate β cell function.

Results

The average age of participants was 58.5 years. The prevalence of T2D decreased across the tertiles of eosinophil percentage (21.3%, 18.2% and 16.9%, P<0.0001). Each one tertile increase of eosinophil percentage inversely associated with risk of T2D when referred not only to normal glucose tolerance (NGT) (odds ratio (OR) 0.81, 95% CI 0.76–0.87, P< 0.0001), but also to impaired glucose regulation (OR 0.89, 95% CI 0.83–0.97, P = 0.006), respectively, after adjustment for the confounding factors. Compared with the first tertile, the third tertile of eosinophil percentage associated with a 23% decrease of insulin resistance in NGT participants after full adjustments (P = 0.005). Each 1-standard deviation of increment of eosinophil percentage associated with a 37% decrease of insulin resistance (P = 0.005).

Conclusions

Higher peripheral eosinophil percentage was associated with decreased risk of T2D. The inverse relation to insulin resistance was detected in NGT participants.     

Change in Body Size and Mortality: Results from the Melbourne Collaborative Cohort Study

Background

The association between change in weight or body mass index, and mortality is widely reported, however, both measures fail to account for fat distribution. Change in waist circumference, a measure of central adiposity, in relation to mortality has not been studied extensively.

Methods

We investigated the association between mortality and changes in directly measured waist circumference, hips circumference and weight from baseline (1990–1994) to wave 2 (2003–2007) in a prospective cohort study of people aged 40–69 years at baseline. Cox regression, with age as the time metric and follow-up starting at wave 2, adjusted for confounding variables, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for change in body size in relation to mortality from all causes, cardiovascular disease and cancer.

Results

There were 1465 deaths (109 cancer, 242 cardiovascular disease) identified during an average 7.7 years of follow-up from 21 298 participants. Compared to minimal increase in body size, loss of waist circumference (HR: 1.26; 95% CI: 1.09–1.47), weight (1.80; 1.54–2.11), or hips circumference (1.35; 1.15–1.57) were associated with an increased risk of all-cause mortality, particularly for older adults. Weight loss was associated with cardiovascular disease mortality (2.40; 1.57–3.65) but change in body size was not associated with obesity-related cancer mortality.

Conclusion

This study confirms the association between weight loss and increased mortality from all-causes for older adults. Based on evidence from observational cohort studies, weight stability may be the recommended option for most adults, especially older adults.     

How Well Can Centenarians Hear?

With advancements in modern medicine and significant improvements in life conditions in the past four decades, the elderly population is rapidly expanding. There is a growing number of those aged 100 years and older. While many changes in the human body occur with physiological aging, as many as 35% to 50% of the population aged 65 to 75 years have presbycusis. Presbycusis is a progressive sensorineural hearing loss that occurs as people get older. There are many studies of the prevalence of age-related hearing loss in the United States, Europe, and Asia. However, no audiological assessment of the population aged 100 years and older has been done. Therefore, it is not clear how well centenarians can hear. We measured middle ear impedance, pure-tone behavioral thresholds, and distortion-product otoacoustic emission from 74 centenarians living in the city of Shaoxing, China, to evaluate their middle and inner ear functions. We show that most centenarian listeners had an “As” type tympanogram, suggesting reduced static compliance of the tympanic membrane. Hearing threshold tests using pure-tone audiometry show that all centenarian subjects had varying degrees of hearing loss. More than 90% suffered from moderate to severe (41 to 80 dB) hearing loss below 2,000 Hz, and profound (>81 dB) hearing loss at 4,000 and 8,000 Hz. Otoacoustic emission, which is generated by the active process of cochlear outer hair cells, was undetectable in the majority of listeners. Our study shows the extent and severity of hearing loss in the centenarian population and represents the first audiological assessment of their middle and inner ear functions.     

Hearing ability with age in northern European women: a new web-based approach to genetic studies

Age-related hearing impairment (ARHI) affects 25-40% of individuals over the age of 65. Despite the high prevalence of this complex trait, ARHI is still poorly understood. We hypothesized that variance in hearing ability with age is largely determined by genetic factors. We collected audiologic data on females of Northern European ancestry and compared different audiogram representations. A web-based speech-to-noise ratio (SNR) hearing test was compared with pure-tone thresholds to see if we could determine accurately hearing ability on people at home and the genetic contribution to each trait compared. Volunteers were recruited from the TwinsUK cohort. Hearing ability was determined using pure-tone audiometry and a web-based hearing test. Different audiogram presentations were compared for age-correlation and reflection of audiogram shape. Using structural equation modelling based on the classical twin model the heritability of ARHI, as measured by the different phenotypes, was estimated and shared variance between the web-based SNR test and pure-tone audiometry determined using bivariate modelling. Pure-tone audiometric data was collected on 1033 older females (age: 41-86). 1970 volunteers (males and females, age: 18-85) participated in the SNR. In the comparison between different ARHI phenotypes the difference between the first two principle components (PC1-PC2) best represented ARHI. The SNR test showed a sensitivity and specificity of 89% and 80%, respectively, in comparison with pure-tone audiogram data. Univariate heritability estimates ranged from 0.70 (95% CI: 0.63-0.76) for (PC1-PC2) to 0.56 (95% CI: 0.48-0.63) for PC2. The genetic correlation of PC1-PC2 and SNR was -0.67 showing that the 2 traits share variances attributed to additive genetic factors. Hearing ability showed considerable heritability in our sample. We have shown that the SNR test provides a useful surrogate marker of hearing. This will enable a much larger sample to be collected at a fraction of the cost, facilitating future genetic association studies.     

Inverse Relationship between Serum Lipoxin A4 Level and the Risk of Metabolic Syndrome in a Middle-Aged Chinese Population

Metabolic syndrome (MetS) has been identified to be associated with a state of chronic, low-grade inflammation in adipose tissue. Lipoxins are endogenously generated from arachidonic acid, and exhibit anti-inflammatory actions. Currently, there is no available cohort study identifying the association between serum lipoxins level and MetS. Here we investigate the relationship between serum lipoxin A4 (LXA4) level and the risk of incident MetS in a middle-aged Chinese population. A total 624 participants aged 40–65 years were enrolled at baseline, with 417 (including 333 MetS absence) of them were followed up at 2.5 years. Abdominal visceral fat area (VFA) and abdominal subcutaneous fat area (SFA) were determined using MRI. Serum lipoxin A4 levels were measured by ELISA. At baseline, serum LXA4 levels were significantly correlated with a cluster of traditional MetS risk factors related to obesity (P≤0.05). A higher incidence of new Mets was found in the participants of the lowest tertile of LXA4 levels as compared with that in participants of the highest tertile (P = 0.025). Low serum LXA4 levels [OR 2.607(1.151–5.909), P = 0.022] and high VFA [OR 2.571(1.176–5.620), P = 0.018] were associated with an increased incident Mets, respectively, which remained statistically significant after adjustment for age, gender, current smoking, and alcohol drinking status. Logistic regression analysis suggested a combination of low serum LXA4 levels and high WC/VFA might optimize the prediction of incident Mets in middle-aged Chinese population [OR 4.897/4.967, P = 0.009/0.003]. Decrease in serum LXA4 level and increase in VFA are independent predictors of incident Mets in a population-based cohort, and a combination of them enhances the prognostic value of incident Mets. Taken together, our data suggest that serum LXA4 levels might be useful for early detection and prevention of Mets.     

Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait

Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-sectional family-based genetic study employing audiometric data. By using principal component analysis, we were able to reduce the dimensionality of this multivariate phenotype while capturing most of the variation and retaining biologically important features of the audiograms. We conducted a genome-wide association as well as a linkage scan with high-density SNP microarrays. Because of the presence of genetic population substructure, association testing was stratified after which evidence was combined by meta-analysis. No association signals reaching genome-wide significance were detected. Linkage analysis identified a linkage peak on 8q24.13-q24.22 for a trait correlated to audiogram shape. The signal reached genome-wide significance, as assessed by simulations. This finding represents the first locus for an ARHI trait.     

Risk factors for infection with chikungunya and Zika viruses in southern Puerto Rico: A community-based cross-sectional seroprevalence survey

Chikungunya virus (CHIKV) caused a large outbreak in Puerto Rico in 2014, followed by a Zika virus (ZIKV) outbreak in 2016. Communities Organized for the Prevention of Arboviruses (COPA) is a cohort study in southern Puerto Rico, initiated in 2018 to measure arboviral disease risk and provide a platform to evaluate interventions. To identify risk factors for infection, we assessed prevalence of previous CHIKV infection and recent ZIKV and DENV infection in a cross-sectional study among COPA participants. Participants aged 1–50 years (y) were recruited from randomly selected households in study clusters. Each participant completed an interview and provided a blood specimen, which was tested by anti-CHIKV IgG ELISA assay and anti-ZIKV and anti-DENV IgM MAC-ELISA assays. We assessed individual, household, and community factors associated with a positive result for CHIKV or ZIKV after adjusting for confounders. During 2018–2019, 4,090 participants were enrolled; 61% were female and median age was 28y (interquartile range [IQR]: 16–41). Among 4,035 participants tested for CHIKV, 1,268 (31.4%) had evidence of previous infection. CHIKV infection prevalence was lower among children 1–10 years old compared to people 11 and older (adjusted odds ratio [aOR] 2.30; 95% CI 1.71–3.08). Lower CHIKV infection prevalence was associated with home screens (aOR 0.51; 95% CI 0.42–0.61) and air conditioning (aOR 0.64; 95% CI 0.54–0.77). CHIKV infection prevalence also varied by study cluster of residence and insurance type. Few participants (16; 0.4%) had evidence of recent DENV infection by IgM. Among 4,035 participants tested for ZIKV, 651 (16%) had evidence of recent infection. Infection prevalence increased with older age, from 7% among 1–10y olds up to 19% among 41–50y olds (aOR 3.23; 95% CI 2.16–4.84). Males had an increased risk of Zika infection prevalence compared with females (aOR 1.31; 95% CI 1.09–1.57). ZIKV infection prevalence also decreased with the presence of home screens (aOR 0.66; 95% CI 0.54–0.82) and air conditioning (aOR 0.69; 95% CI 0.57–0.84). Similar infection patterns were observed for recent ZIKV infection prevalence and previous CHIKV infection prevalence by age, and the presence of screens and air conditioners in the home decreased infection risk from both viruses by as much as 50%.