Clinical Manifestations.

Background: Endogenous estrogen history across the life course may be associated with better cognitive maintenance. Few large longitudinal studies have evaluated this prospectively, and results have been inconsistent. We assessed the association of reproductive span, an indicator of endogenous estrogen history, with cognitive change in older women.

Cross-sectional analysis of plasma n-3 fatty acid levels and self-reported hearing difficulty in the UK Biobank Cohort.

Background: Disabling hearing loss affects ∼430 million people globally. Fish consumption and long-chain n-3 polyunsaturated fatty acid (PUFA) intake were inversely associated with risk of hearing loss, but the association of plasma n-3 PUFAs and hearing loss is unclear.

Objective: To examine the associations between plasma n-3 PUFA fractions (as % of total fatty acids), i.

New Quadratic Discriminant Analysis Algorithms for Correlated Audiometric Data.

Paired organs like eyes, ears, and lungs in humans exhibit similarities, and data from these organs often display remarkable correlations. Accounting for these correlations could enhance classification models used in predicting disease phenotypes. To our knowledge, there is limited, if any, literature addressing this topic, and existing methods do not exploit such correlations.

Longitudinal study of seafood and fish oil supplement intake and risk of persistent tinnitus.

Background: Persistent tinnitus is common, disabling, and difficult to treat. Diet has been implicated in tinnitus etiology, but studies are inconsistent, and longitudinal data are scarce. Seafood intake is associated with a lower risk of hearing loss, but the longitudinal association with tinnitus is unknown.

Herpes zoster and long-term risk of subjective cognitive decline.

Background: Herpes zoster (HZ), commonly known as "shingles," may contribute to cognitive decline through mechanisms such as neuroinflammation or direct neuronal injury. However, evidence on the longitudinal association between HZ and cognitive decline is conflicting and whether the risk differs by APOE ε4-carrier status has not been studied; prospective cohort studies on the association between HZ vaccination and cognitive decline are also lacking.

Methods: We included 149,327 participants from three large cohorts-the Nurses' Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (HPFS)-to prospectively examine the association between HZ and subsequent subjective cognitive decline (SCD).

Estimating intracluster correlation for ordinal data.

In this paper, we consider the estimation of intracluster correlation for ordinal data. We focus on pure-tone audiometry hearing threshold data, where thresholds are measured in 5 decibel increments. We estimate the intracluster correlation for tests from iPhone-based hearing assessment applications as a measure of test/retest reliability.

Hypothesis Tests for Continuous Audiometric Threshold Data.

Objectives: Hypothesis tests for hearing threshold data may be challenging due to the special structure of the response variable, which consists of the measurements from the participant's two ears at multiple frequencies. The commonly-used methods may have inflated type I error rates for the global test that examines whether exposure-hearing threshold associations exist in at least one of the frequencies. We propose using both-ear methods, including all frequencies in the same model for hypothesis testing.

Soft classification and regression analysis of audiometric phenotypes of age-related hearing loss.

Age-related hearing loss has a complex etiology. Researchers have made efforts to classify relevant audiometric phenotypes, aiming to enhance medical interventions and improve hearing health. We leveraged existing pattern analyses of age-related hearing loss and implemented the phenotype classification via quadratic discriminant analysis (QDA).

Sex differences in the pleiotropy of hearing difficulty with imaging-derived phenotypes: a brain-wide investigation.

Hearing difficulty (HD) is a major health burden in older adults. While ageing-related changes in the peripheral auditory system play an important role, genetic variation associated with brain structure and function could also be involved in HD predisposition. We analysed a large-scale HD genome-wide association study (GWAS; ntotal = 501 825, 56% females) and GWAS data related to 3935 brain imaging-derived phenotypes (IDPs) assessed in up to 33 224 individuals (52% females) using multiple MRI modalities.

Sex differences in the pleiotropy of hearing difficulty with imaging-derived phenotypes: a brain-wide investigation.

Background: Hearing difficulty (HD) is one of the major health burdens in older adults. While aging-related changes in the peripheral auditory system play an important role, genetic variation associated with brain structure and function could also be involved in HD predisposition.

Methods: We analyzed a large-scale HD genome-wide association study (GWAS; N = 501,825, 56% females) and GWAS data related to 3,935 brain imaging-derived phenotypes (IDPs) assessed in up to 33,224 individuals (52% females) using multiple magnetic resonance imaging (MRI) modalities.

Analytical method for detecting outlier evaluators.

Background: Epidemiologic and medical studies often rely on evaluators to obtain measurements of exposures or outcomes for study participants, and valid estimates of associations depends on the quality of data. Even though statistical methods have been proposed to adjust for measurement errors, they often rely on unverifiable assumptions and could lead to biased estimates if those assumptions are violated. Therefore, methods for detecting potential 'outlier' evaluators are needed to improve data quality during data collection stage.

Sex differences in the polygenic architecture of hearing problems in adults.

Background: Hearing problems (HP) in adults are common and are associated with several comorbid conditions. Its prevalence increases with age, reflecting the cumulative effect of environmental factors and genetic predisposition. Although several risk loci have been already identified, HP biology and epidemiology are still insufficiently investigated by large-scale genetic studies.

Association of Plasma Metabolomic Biomarkers With Persistent Tinnitus: A Population-Based Case-Control Study.

Importance: Persistent tinnitus is common, disabling, and difficult to treat.

Objective: To evaluate the association between circulating metabolites and persistent tinnitus.

Design, Setting, And Participants: This was a population-based case-control study of 6477 women who were participants in the Nurses' Health Study (NHS) and NHS II with metabolomic profiles and tinnitus data.

Associations of Tinnitus Incidence with Use of Tumor Necrosis Factor-Alpha Inhibitors among Patients with Autoimmune Conditions.

Tumor necrosis factor-alpha (TNFα) may promote neuroinflammation prompting tinnitus. This retrospective cohort study evaluated whether anti-TNFα therapy influences incident tinnitus risk among adults with autoimmune disorders and no baseline tinnitus selected from a US electronic health records database (Eversana; 1 January 2010-27 January 2022). Patients with anti-TNFα had ≥90-day history pre-index (first autoimmune disorder diagnosis) and ≥180-day follow-up post-index.

Analytical methods for correlated data arising from multicenter hearing studies.

In epidemiological hearing studies, estimating the association between exposures and hearing loss using audiometrically-assessed hearing measurements is challenging due to the complex correlation structure in the clustered data, with clusters formed by the two ears of the same individual and the testing site and audiologist. We propose a linear mixed-effects model to take into account the multilevel correlation structures of the data. Both theoretically and in simulation studies, we compare single-ear linear regression models commonly used in published hearing loss studies with the proposed both-ears linear mixed models properly accounting for the multi-level correlations.

Both-Ear Method for the Analysis of Audiometric Data.

Objective: Single-ear hearing measurements, such as better-ear, worse-ear or left/right ear, are often used as outcomes in auditory research, yet, measurements in the two ears of the same individual are often strongly but not perfectly correlated. We propose a both-ear method using the Generalized Estimating Equation approach for analysis of correlated binary ear data to evaluate determinants of ear-specific outcomes that includes information from both ears of the same individual.

Design: We first theoretically evaluated bias in odds ratio (OR) estimates based on worse-ear and better-ear hearing outcomes.

Longitudinal Study of Analgesic Use and Risk of Incident Persistent Tinnitus.

Background: Persistent tinnitus is common, disabling, and difficult to treat. High-dose aspirin may precipitate tinnitus, but longitudinal data on typical dose aspirin and other analgesics are scarce.

Objective: To investigate independent associations of aspirin, NSAIDs, and acetaminophen and risk of incident persistent tinnitus.

Osteoporosis, bisphosphonate use, and risk of moderate or worse hearing loss in women.

Background: Osteoporosis and low bone density (LBD) may be associated with higher risk of hearing loss, but findings are inconsistent and longitudinal data are scarce. Bisphosphonates may influence risk, but the relation has not been studied in humans. We longitudinally investigated associations of osteoporosis and LBD, bisphosphonate use, vertebral fracture (VF), hip fracture (HF), and risk of self-reported moderate or worse hearing loss.

Tinnitus and 3-Year Change in Audiometric Hearing Thresholds.

Objectives: Tinnitus and hearing loss commonly coexist, however, the temporal relation between tinnitus and hearing loss is complex and not fully understood. Our objective was to examine the longitudinal association between persistent tinnitus, bothersome tinnitus, and 3-year elevation of audiometric hearing thresholds.

Design: We conducted a longitudinal cohort study among 3106 women (mean age 59 years) who were participants in the Nurses' Health Study II (2012-2018).

Cigarette Smoking, Smoking Cessation, and Risk of Hearing Loss in Women.

Background: Previous studies demonstrated higher risk of hearing loss among cigarette smokers, but longitudinal data on whether the risk is influenced by smoking cessation are limited. We prospectively investigated relations between smoking, smoking cessation, and risk of self-reported moderate or worse hearing loss among 81,505 women in the Nurses' Health Study II (1991-2013).

Methods: Information on smoking and hearing status was obtained from validated biennial questionnaires.

Birth Weight and Adult-Onset Hearing Loss.

Objectives: Among low-birth-weight infants, exposure to stress or undernutrition in utero may adversely affect cochlear development. As cochlear reserve declines, the risk of hearing loss may increase with age. While low birth weight is associated with a higher risk of neonatal hearing loss, our objective was to examine whether birth weight was associated with adult-onset, self-reported hearing loss in the Nurses' Health Studies (NHS) I and II (n = 113,130).

Ultraviolet Radiation Exposure and the Risk of Herpes Zoster in Three Prospective Cohort Studies.

Objective: To examine the association between ultraviolet radiation (UVR) exposure and the risk of herpes zoster (HZ) in 3 prospective cohorts.

Patients And Methods: We included 205,756 participants from the Health Professionals Follow-up Study (HPFS; 1986-2008), Nurses' Health Study (NHS; 1996-2012), and Nurses' Health Study II (NHS II; 1991-2013). Ambient UVR exposure was based on updated geocoded address histories linked with a high-resolution spatiotemporal ultraviolet model.

Longitudinal study of self-reported hearing loss and subjective cognitive function decline in women.

Introduction: We investigated the relation between self-reported hearing loss and risk of subjective cognitive function (SCF) decline among women.

Methods: We conducted a longitudinal study of 20,193 women in the Nurses' Health Study aged ≥66 years who reported their hearing status and had no subjective cognitive concerns in 2012. SCF scores were assessed by a 7-item questionnaire in 2012 and 2014.