Objective: Evidence from observational epidemiology studies suggested that renal dysfunction was associated with hearing loss. Whether this represents a causal, reverse causal or correlative relationship remains unclear. We investigated this using a bidirectional two-sample Mendelian Randomization (MR) approach. Methods: We retrieved genetic variants associated with renal function biomarkers, including creatinine-based eGFR (eGFR-crea), cystatin C-based eGFR (eGFR-cys), urine albumin-to-creatinine ratio (UACR), and serum urate, from the CKDGen Consortium. The summary-level datasets of hearing loss were retrieved from the GWAS of UK Biobank. Inverse-Variance Weighted (IVW) method was the main analysis. Results: The MR analysis revealed a significant association between genetically predicted UACR and the risk of hearing loss (IVW: OR = 1.038, 95% CI 1.002-1.074, p = 0.036). However, we did not find evidence for a causal effect of eGFR-crea (IVW: OR = 1.046, 95% CI 0.953-1.149, p = 0.342), eGFR-cys (IVW: OR = 0.997, 95% CI 0.940-1.058, p = 0.932) and urate (IVW: OR = 0.999, 95% CI 0.990-1.009, p = 0.904) on hearing loss. Moreover, we found no evidence that hearing loss had causal effects on renal function in the reverse MR analyses. Sensitivity analyses also confirmed the robustness of these findings. Conclusion: This study provides genetic evidence that elevated UACR is a potential risk factor for hearing loss, but does not support a causal role of hearing loss on kidney function. Level of evidence: Level 2.

Objective:Otolith is a critical component of the peripheral vestibular system responsible for detecting linear acceleration. Dysfunction of the otolith organs can lead to vertigo, balance disturbances, and gaze instability. By elucidating the physiological foundations and evaluating both current and emerging methods for assessing otolith function, this review aims to provide a comprehensive resource for researchers and clinicians in the field of vestibular science, contributing to improved diagnostic accuracy and the development of more effective therapeutic strategies. Data Sources:The databases of PubMed, Embase, and Cochrane Library were systematically searched for the articles. Methods:The information of physiological mechanism and clinical significance were extracted from each article. Results:Vestibular-evoked myogenic potentials (VEMPs) are valuable for evaluating saccule and utricle function, with clinical applications in diagnosing several diseases. Subjective visual vertical (SVV) has clinical value in the diagnosis of peripheral and central vestibular diseases, with recent advancements in smartphone Apps and VR devices providing more accessibility. The ocular counter-roll (OCR) examination has a superior application prospect, but standardization including the normal range and duration of recovery, was incomplete. The off-vertical axis rotation (OVAR) can be used to explore motion sickness. The test of linear acceleration perception is limited by device, site and result instability, so it is difficult to apply clinically. Balance-related tests have been applied clinically, but the isolation of otolith components that determine balance is an unfinished task. Conclusion:The review emphasizes the need for more precise and standardized otolith function tests to enhance diagnostic accuracy and therapeutic strategies, ultimately improving patient outcomes in vestibular disorders.

Individuals with vestibular dysfunction frequently experience dizziness, nausea and imbalance in visually complex or dynamic environments, such as during computer use, shopping, walking in crowds or even during simple eye movements. To determine whether binocular visual function differs between participants with vestibular dysfunction and healthy controls, and to identify clinical factors associated with binocular visual abnormalities. Forty participants with vestibular dysfunction and forty healthy controls were enroled. Binocular visual function was assessed using tests of suppression, perceptual eye position, vergence range and stereopsis. Between-group differences were analysed. Logistic regression was performed to identify factors associated with binocular visual function abnormalities. Receiver operating characteristic (ROC) analyses were conducted to evaluate the discriminative ability of binocular visual parameters. Compared with controls, participants with vestibular dysfunction demonstrated significantly diminished convergence, divergence and stereopsis, while no significant differences were observed in suppression or perceptual eye position. Vestibular dysfunction was independently associated with abnormal convergence (odds ratio (OR) = 47.67, 95

The vestibular system, a crucial sensorimotor apparatus for balance and spatial orientation, is regulated by neurotransmitters. Despite its essential function, the intricacies of neurotransmission within this system, particularly regarding monoamine neurotransmitters, remain not fully explained. A variety of vestibular disorders and therapeutic interventions are associated with balance regulation, underscoring the significance of understanding the neurotransmission in the vestibular system. This comprehensive review offers an overall insight into the role of monoamine neurotransmitters, including serotonin (5-HT), histamine, dopamine, and norepinephrine (NE), in the vestibular compensation following peripheral vestibular dysfunction. By examining the existing literature and integrating recent findings, monoamine neurotransmitters are closely associated with vestibular disorders, and their modulators have been used in the treatment of such conditions. Based on the vestibular dysfunction, we highlight the expression and functional significance of these neurotransmitters in the early vestibular compensation. Future research will further explore the role of neurotransmitters and their receptors in vestibular compensation, providing new ideas for the development of more effective treatment strategies.

The vestibular system plays a pivotal role in maintaining body balance and postural stability[1].Its functional disruption can trig-ger a compensatory process termed vestibular compensation,which is fundamental to the rehabilitation from various vestibular pathologies[2].

AbstractIt remains unclear whether the benefits of adhering to a healthy lifestyle outweigh the effects of high genetic risk on cognitive decline. We examined the association of combined lifestyle factors and genetic risk with changes in cognitive function and six specific dimensions of cognition among older adults from the Chinese Longitudinal Healthy Longevity Survey (1998–2018, n = 18,811, a subset of 6301 participants with genetic information). Compared to participants with an unfavorable lifestyle, those with a favorable lifestyle showed a 46.81% slower rate of cognitive decline, with similar results across most cognitive domains. High genetic risk was associated with a 12.5% faster rate of cognitive decline. Individuals with a high genetic risk and a favorable lifestyle have slower cognitive decline than those with a low genetic risk and an unfavorable lifestyle. These data suggest that the benefits of a favorable lifestyle outweigh genetic factors, and therefore that adhering to a favorable lifestyle may offset the genetic risk for accelerated cognitive decline.

Lower socioeconomic status (SES) is associated with various adverse health outcomes, but its association with healthy ageing is less known, and whether adherence to a healthy lifestyle at late-life years can reduce socioeconomic disparities in health requires further investigation. In a 20-year cohort of 33,541 older adults aged ≥65 years across 23 provinces in China, we investigated socioeconomic disparities in mortality and unhealthy ageing considering physical, cognitive, mental, visual, and hearing functions, and evaluated whether adherence to a healthy lifestyle at late-life years can reduce these health disparities. We categorized SES into low, medium, or high using latent class analysis based on education level, financial status, and occupation, and established the healthy lifestyle score by never smoking, no heavy alcohol consumption, regular physical and leisure activity, and a healthy diet. Compared with older adults of high SES, those of low SES had increased risks of all-cause mortality and unhealthy ageing, with adjusted hazard ratios (HR) and 95% confidence intervals (CI) of 1.25 (1.17, 1.33) and 1.46 (1.33, 1.60), respectively. Overall, a healthy lifestyle mediated 20.5% (16.4, 24.7) and 16.4% (12.0, 20.9) of socioeconomic inequity in all-cause mortality and unhealthy ageing, respectively. In low, medium, and high SES subpopulations, the healthiest lifestyle group had 3.18 (2.69, 3.67), 3.76 (2.85, 4.67), and 5.65 (3.75, 7.55) more years of total life expectancy, and 1.40 (1.06, 1.74), 2.73 (2.09, 3.37), and 3.90 (2.64, 5.16) more years of healthy life expectancy at age 65, respectively, compared to the least healthy group. The findings underscored the urgent need for tailored, accessible interventions in low-SES populations to mitigate health inequities and reinforced the importance of healthy lifestyle promotion, even at late-life years, for healthy ageing and longevity.

The health benefits of physical activity (PA) have been well recognized, while which types of PA are most beneficial are still unclear, especially for older adults. The study aimed to explore associations of different PAs (physical work, regular exercise, and leisure activities) with mortality among Chinese older adults, considering genetic risk. A total of 9690 older adults from the Chinese Longitudinal Health Longevity Survey (CLHLS, 1998–2018) were included. Self-reported PAs information on physical work, regular exercise, and leisure activities were collected through face-to-face interviews. Leisure activities were interviewed about their engagement in 6 typical activities (i.e., housework tasks, personal outdoor activities, gardening, rearing domestic animals/pets, playing cards/mahjong, and attending in social activities). A weighted genetic risk score (GRS) was constructed based on 11 lifespan-related loci and divided into two groups according to the median scores (0.21). The Cox proportional risk model was used to assess the association between different types of PAs and genetic risk with all-cause mortality. During 63,832 person-years of follow-up, 5678 deaths were documented. The hazard ratios (HRs) for all-cause mortality between different PAs (lowest activity vs highest activity) were 0.85 (95

Recent years have seen a burgeoning interest in elucidating the intricate relationship between vestibular dysfunction and sleep disorders, owing to their substantial impact on daily functioning and overall health. Despite significant advancements, the precise mechanisms underpinning this interplay remain elusive. This review aims to synthesize the current literature on the association between vestibular dysfunction and sleep disorders, focusing on potential causal mechanisms and therapeutic implications. We systematically examine various sleep disorders, including insomnia, circadian rhythm disorders, and sleep apnea, in association with specific vestibular dysfunctions, such as Meniere's disease (MD), vestibular migraine (VM), benign paroxysmal positional vertigo (BPPV), vestibular neuritis (VN), and persistent postural perceptual dizziness (PPPD). By exploring these complex interactions, our goal is to provide a comprehensive understanding that contributes to the ongoing discourse in this field. We seek to encourage further investigations into innovative diagnostic and therapeutic strategies, ultimately aiming to improve the clinical management and enhance the quality of life for patients affected by both vestibular dysfunction and sleep disorders.

Body mass index(BMI)is widely recognized as a reasonably good measure of general adiposity and an important predictor of mortality risk[1].Meta-analyses of cohort studies[2]have demon-strated a"U"or"J"-shaped correlation,wherein both low and high BMI values are associated with an increased risk of mortality.

The vestibular system may have a critical role in the integration of sensory information and the maintenance of cognitive function. A dysfunction in the vestibular system has a significant impact on quality of life. Recent research has provided evidence of a connection between vestibular information and cognitive functions, such as spatial memory, navigation and attention. Although the exact mechanisms linking the vestibular system to cognition remain elusive, researchers have identified various pathways. Vestibular dysfunction may lead to the degeneration of cortical vestibular network regions and adversely affect synaptic plasticity and neurogenesis in the hippocampus, ultimately contributing to neuronal atrophy and cell death, resulting in memory and visuospatial deficits. Furthermore, the extent of cognitive impairment varies depending on the specific type of vestibular disease. In the present study, the current literature was reviewed, potential causal relationships between vestibular dysfunction and cognitive performance were discussed and directions for future research were proposed.

What is already known about this topic?:Antimony (Sb) has been identified as a new neurotoxicant that impacts neurological functions in animal studies. However, its effects on the human population remain unknown. What is added by this report?:The study reveals that there is an association between exposure to Sb and a higher incidence of cognitive impairment in older adults. The dose-response curve demonstrates that the risk of cognitive impairment consistently increased with higher levels of Sb exposure without a discernible threshold. What are the implications for public health practice?:Reducing exposure to Sb may have a beneficial effect in delaying or preventing the onset of cognitive impairment. This intervention has the potential to significantly decrease the disease burden associated with cognitive impairment, ultimately contributing to social development.

Objective The associations between plasma vitamin B 12 level and anemia under different dietary patterns in elderly Chinese people are poorly understood. We aimed to examine the associations between plasma vitamin B 12 levels and anemia under different dietary patterns in adults aged 65 years and older in nine longevity areas in China. Methods A total of 2405 older adults completed a food frequency questionnaire at the same time as a face-to-face interview. The dietary diversity score (DDS) was assessed based on the food frequency questionnaire, with the low DDS group referring to participants with a DDS score ≤ 4 points. Vitamin B 12 levels were divided into two groups of high (>295 pg/mL) and low (≤ 295 pg/mL) with the median used as the cut-off point. Sub-analyses were also performed on older adults divided into tertiles of vitamin B 12 levels: low (< 277 pg/mL), medium (277–375 pg/mL) and high (> 375 pg/mL) to study the association of these levels with anemia. Results Six hundred ninety-five (28.89%) of these people were diagnosed with anemia and had a mean age of 89.3 years. Higher vitamin B 12 levels were associated with a decreased risk of anemia (multi-adjusted OR, 0.59, [95% CI, 0.45 ~ 0.77] P < 0.001) in older adults with a low DDS, whereas no significant association between vitamin B 12 levels and anemia was found in older adults with a high DDS in a full-model after adjustment for various confounding factors (multi-adjusted OR, 0.88, [95% CI, 0.65 ~ 1.19], P = 0.41). Conclusion The relationship between vitamin B 12 levels and the prevalence of anemia was significant only when the level of dietary diversity in the older adults was relatively low. The dietary structure of the population should be taken into consideration in combination in order to effectively improve anemia status by supplementing vitamin B 12 .

Noise-induced hearing loss (NIHL) is a prevalent form of adult hearing impairment, characterized by oxidative damage to auditory sensory hair cells. Although certain dihydropyridines, the L-type calcium channel blockers, exhibit protective properties against such damage, the ability of third-generation dihydropryidines like lercanidipine to mitigate NIHL remains unclear.We utilized glucose oxidase (GO)-treated OC1 cell lines and cochlear explants to evaluate the protective influence of lercanidipine on hair cells. To further investigate its effectiveness, we exposed noise-stimulated mice in vivo and analyzed their hearing thresholds. Additionally, we assessed the antioxidative capabilities of lercanidipine by examining oxidation-related enzyme expression and levels of oxidative stress markers, including 3-nitrotyrosine (3NT) and 4-hydroxynonenal (4HNE). Our findings demonstrate that lercanidipine significantly reduces the adverse impacts of GO on both OC-1 cell viability (0.3 to 2.5 µM) and outer hair cell (OHC) survival in basal turn cochlear explants (7 µM). These results are associated with increased mRNA expression of antioxidant enzyme genes (HO-1, SOD1/2, and Txnrd1), along with decreased expression of oxidase genes (COX-2, iNOS). Crucially, lercanidipine administration prior to, and following, noise exposure effectively ameliorates NIHL, as evidenced by lowered hearing thresholds and preserved OHC populations in the basal turn, 14 days post-noise stimulation at 110 dB SPL. Moreover, our observations indicate that lercanidipine’s antioxidative action persists even three days after simultaneous drug and noise treatments, based on 3-nitrotyrosine and 4-hydroxynonenal immunostaining in the basal turn. Based on these findings, we propose that lercanidipine has the capacity to alleviate NIHL and safeguard OHC survival in the basal turn, potentially via its antioxidative mechanism. These results suggest that lercanidipine holds promise as a clinically viable option for preventing NIHL in affected individuals.

BACKGROUND AND AIMS:Emerging evidence has raised an obesity paradox in observational studies of body mass index (BMI) and health among the oldest-old (aged ≥80 years), as an inverse relationship of BMI with mortality was reported. This study was to investigate the causal associations of BMI, waist circumference (WC), or both with mortality in the oldest-old people in China. METHODS:A total of 5306 community-based oldest-old (mean age 90.6 years) were enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) between 1998 and 2018. Genetic risk scores were constructed from 58 single-nucleotide polymorphisms (SNPs) associated with BMI and 49 SNPs associated with WC to subsequently derive causal estimates for Mendelian randomization (MR) models. One-sample linear MR along with non-linear MR analyses were performed to explore the associations of genetically predicted BMI, WC, and their joint effect with all-cause mortality, cardiovascular disease (CVD) mortality, and non-CVD mortality. RESULTS:During 24 337 person-years of follow-up, 3766 deaths were documented. In observational analyses, higher BMI and WC were both associated with decreased mortality risk [hazard ratio (HR) 0.963, 95% confidence interval (CI) 0.955-0.971 for a 1-kg/m2 increment of BMI and HR 0.971 (95% CI 0.950-0.993) for each 5 cm increase of WC]. Linear MR models indicated that each 1 kg/m2 increase in genetically predicted BMI was monotonically associated with a 4.5% decrease in all-cause mortality risk [HR 0.955 (95% CI 0.928-0.983)]. Non-linear curves showed the lowest mortality risk at the BMI of around 28.0 kg/m2, suggesting that optimal BMI for the oldest-old may be around overweight or mild obesity. Positive monotonic causal associations were observed between WC and all-cause mortality [HR 1.108 (95% CI 1.036-1.185) per 5 cm increase], CVD mortality [HR 1.193 (95% CI 1.064-1.337)], and non-CVD mortality [HR 1.110 (95% CI 1.016-1.212)]. The joint effect analyses indicated that the lowest risk was observed among those with higher BMI and lower WC. CONCLUSIONS:Among the oldest-old, opposite causal associations of BMI and WC with mortality were observed, and a body figure with higher BMI and lower WC could substantially decrease the mortality risk. Guidelines for the weight management should be cautiously designed and implemented among the oldest-old people, considering distinct roles of BMI and WC.

Vestibular compensation is the natural process of recovery that occurs with acute peripheral vestibular lesion. Here, we summarize the current understanding of the mechanisms underlying vestibular compensation, focusing on the role of the medial vestibular nucleus (MVN), the central hub of the vestibular system, and its associated neural networks. The disruption of neural activity balance between the bilateral MVNs underlies the vestibular symptoms after unilateral vestibular damage, and this balance disruption can be partially reversed by the mutual inhibitory projections between the bilateral MVNs, and their top-down regulation by other brain regions via different neurotransmitters. However, the detailed mechanism of how MVN is involved in vestibular compensation and regulated remains largely unknown. A deeper understanding of the vestibular neural network and the neurotransmitter systems involved in vestibular compensation holds promise for improving treatment outcomes and developing more effective interventions for vestibular disorders.

Background Observational studies have demonstrated that a higher resting heart rate (RHR) is associated with an increased risk of dementia. However, it is not clear whether the association is causal. This study aimed to determine the causal effects of higher genetically predicted RHR on the risk of dementia. Methods We performed a two-sample Mendelian randomization analysis to investigate the causal effect of higher genetically predicted RHR on Alzheimer’s disease (AD) using summary statistics from genome-wide association studies. The generalized summary Mendelian randomization (GSMR) analysis was used to analyze the corresponding effects of RHR on following different outcomes: 1) diagnosis of AD (International Genomics of Alzheimer’s Project), 2) family history (maternal and paternal) of AD from UK Biobank, 3) combined meta-analysis including these three GWAS results. Further analyses were conducted to determine the possibility of reverse causal association by adjusting for RHR modifying medication. Results The results of GSMR showed no significant causal effect of higher genetically predicted RHR on the risk of AD (βGSMR = 0.12, P = 0.30). GSMR applied to the maternal family history of AD (βGSMR = −0.18, P = 0.13) and to the paternal family history of AD (βGSMR = −0.14, P = 0.39) showed the same results. Furthermore, the results were robust after adjusting for RHR modifying drugs (βGSMR = −0.03, P = 0.72). Conclusion Our study did not find any evidence that supports a causal effect of RHR on dementia. Previous observational associations between RHR and dementia are likely attributed to the correlation between RHR and other cardiovascular diseases.