Long-term NAD+ supplementation prevents the progression of age-related hearing loss in mice.

Age-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this debilitating condition. With its slow progression, continuous and safe approaches are critical for ARHL treatment. Nicotinamide Riboside (NR), a NAD+ precursor, is well tolerated even for long-term use and is already shown effective in various disease models including Alzheimer's and Parkinson's disease. It has also been beneficial against noise-induced hearing loss and in hearing loss associated with premature aging. However, its beneficial impact on ARHL is not known. Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL. Through transcriptomic and biochemical analysis, we find that NR administration restores age-associated reduction in cochlear NAD+ levels, upregulates biological pathways associated with synaptic transmission and PPAR signaling, and reduces the number of orphan ribbon synapses between afferent auditory neurons and inner hair cells. We also find that NR targets a novel pathway of lipid droplets in the cochlea by inducing the expression of CIDEC and PLIN1 proteins that are downstream of PPAR signaling and are key for lipid droplet growth. Taken together, our results demonstrate the therapeutic potential of NR treatment for ARHL and provide novel insights into its mechanism of action.

Melatonin Suppresses Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Signaling and Delays the Development of Hearing Loss in the C57BL/6J Presbycusis Mouse Model.

Melatonin supplementation has been shown to delay age-related hearing loss (ARHL) progression. Previously, melatonin was found to inhibit neuronal mitochondrial DNA (mtDNA) release, as well as inhibit cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling, thereby delaying the onset of central nervous system diseases. Therefore, we hypothesized that melatonin may delay the progression of hearing loss in the C57BL/6J presbycusis mouse model by inhibiting cGAS-STING signaling in the auditory pathway. Oral melatonin at 10 mg/kg/d was administered to 3-month-old C57BL/6J mice until 12 months of age. The auditory brainstem response (ABR) threshold was used to assess their hearing ability. By real-time polymerase chain reaction and Western blot analysis, the levels of cytosolic mtDNA, cGAS/STING, and cytokines were examined in the mouse cochlea, inferior colliculus, and auditory cortex. We found that the 12-month-old control mice exhibited significant hearing loss, increased cytosolic mtDNA, increased expression of inflammatory factors TNF-α, IL-6, IFN-ß, Cxcl10, and Ifit3, up-regulated cGAS and STING expression, and enhanced interferon regulatory factor 3 (IRF3) phosphorylation in the C57BL/6J mouse cochlea, inferior colliculus, and auditory cortex. Melatonin treatment significantly improved hearing, decreased cytosolic mtDNA, suppressed the expression of inflammatory cytokines TNF-α, IL-6, IFN-ß, Ifit3, and Cxcl10, down-regulated cGAS and STING expression, and attenuated IRF3 phosphorylation in the C57BL/6J mouse cochlea, inferior colliculus, and auditory cortex. This study suggested that melatonin had a protective effect on auditory function in the C57BL/6J presbycusis mouse model, which may be mediated through reducing mtDNA release, inhibiting the cGAS-STING signaling pathway in the auditory pathway.

Negative self-perception of hearing and depression in older adults: a population-based study / Autopercepção negativa da audição e depressão em idosos: um estudo de base populacional

ABSTRACT OBJECTIVE To estimate the association between negative self-perception of hearing and depression in older adults in Southern Brazil. METHODS This is a cross-sectional study conducted with data from the third wave of the EpiFloripa Idoso 2017/19 study, a population-based cohort of older adults (60+). A total of 1,335 older adults participated in this wave. The dependent variable was self-reported depression, and the main exposure was self-perception of hearing (negative; positive). For both the crude (bivariate) and adjusted analysis, the odds ratio (OR) was used as a measure of association and estimated by means of binary logistic regression analysis. The exposure variable was adjusted by sociodemographic and health covariates. A p value < 0.05 was adopted as statistically significant. RESULTS The prevalence of negative self-perception of hearing and depression was 26.0% and 21.8%, respectively. In the adjusted analysis, the older adults with negative self-perception of hearing were 1.96 times more likely to report depression when compared to the ones with positive self-perception of hearing (p = 0.002). CONCLUSION The association between negative self-perception of hearing and depression reflects the importance of reviewing health care actions for older adults, incorporating hearing-related issues, to ensure comprehensive care for this growing segment of the population.

RESUMO OBJETIVO Estimar a associação entre a autopercepção negativa da audição e a depressão em idosos do sul do Brasil. MÉTODOS Trata-se de um estudo transversal realizado com dados da terceira onda do estudo EpiFloripa Idoso 2017/19, de coorte de base populacional de idosos (60+). Participaram desta onda 1.335 idosos. A variável dependente foi a depressão autorreferida e a exposição principal foi a autopercepção auditiva (negativa; positiva). Tanto para a análise bruta (bivariada) quanto para a ajustada, a odds ratio (OR) foi utilizada como medida de associação e estimada por meio da análise de Regressão Logística Binária. A variável de exposição foi ajustada pelas covariáveis sociodemográficas e de saúde. Adotou-se o valor de p < 0,05 como estatisticamente significativo. RESULTADOS A prevalência da autopercepção negativa da audição e depressão foi de 26,0% e 21,8%, respectivamente. Na análise ajustada, idosos com autopercepção negativa da audição apresentaram 1,96 vezes mais chance de referirem depressão quando comparados aos idosos com autopercepção positiva da audição (p = 0,002). CONCLUSÃO A associação encontrada entre a autopercepção negativa auditiva e a depressão reflete a importância de rever as ações de atenção à saúde do idoso, incorporando questões relacionadas à audição para a garantia da atenção integral a esta parcela crescente da população.

Thymoquinone ameliorates age-related hearing loss in C57BL/6J mice by modulating Sirt1 activity and Bak1 expression.

Age-related hearing loss (AHL) is the most common sensory disorder of aged population. Currently, one of the most important sources of experimental medicine for AHL is medicinal plants. This study performed the first investigation of the effect of thymoquinone (TQ), a potent antioxidant, on AHL. Here, we used inbred C57BL/6J mice (B6 mice) as a successful experimental model of the early onset of AHL. The behavioral assessment of hearing revealed that the injection of a high dose of TQ (40 mg/kg; TQ40) significantly improved the auditory sensitivity of B6 mice at all tested frequencies (8, 16 and 22 kHz). Histological sections of cochlea from B6 mice injected with a low dose (20 mg/kg; TQ20) and high dose showed relatively less degenerative signs in the modiolus, hair cells and spiral ligaments, the main constituents of the cochlea. In addition, TQ40 completely restored the normal pattern of hair cells in B6 mice, as shown in scanning electron micrographs. Our data indicated that TQ20 and TQ40 reduced levels of Bak1-mediated apoptosis in the cochlea of B6 mice. Interestingly, the level of Sirt1, a positive regulator of autophagy, was significantly increased in B6 mice administered TQ40. In conclusion, TQ relieves the symptoms of AHL by downregulating Bak1 and activating Sirt1 in the cochlea of B6 mice.

Efeito do treinamento musical em idosos candidatos ao uso de próteses auditivas / Effect of musical training in older adults candidates to the use of hearing aids / Efecto de la formación musical en ancianos candidatos al uso de audífonos

Introdução: Associação entre adaptação de próteses auditivas e treinamento auditivo pode melhorar a comunicação do indivíduo e reduzir os déficits funcionais. Objetivo: verificar o benefício na qualidade de vida, sintomas depressivos, aspectos cognitivos, resolução temporal e limitação em atividades de vida em idosos com perda auditiva, após adaptação de próteses auditivas associadas ou não ao treinamento auditivo musical. Métodos: Grupo Experimental - GE: cinco idosos (64 a 79 anos) e Grupo Controle - GC: cinco idosos (62 a 77 anos), todos com perda auditiva neurossensorial simétrica de grau moderado. Foram submetidos à anamnese, miniteste de triagem cognitiva CASI-S, avaliação audiológica incluindo Índice Porcentual de Reconhecimento de Fala (IPRF), Client-Oriented Scale of Improvement (COSI), resolução temporal (teste GIN), triagem para sintomas depressivos (EDG-15), questionários de qualidade de vida (SF-36) e de autoavaliação para próteses auditivas (QI-AASI). Todos receberam próteses auditivas, e apenas o GE, o treinamento auditivo musical. Avaliação realizada em três momentos: antes da adaptação das próteses auditivas; 11 semanas após a adaptação das mesmas, sendo o GE submetido ao treinamento musical por sete semanas; e quatro meses depois. Resultados: Não houve diferença entre grupos segundo idade, escolaridade e triagem cognitiva. Todos apresentaram melhores limiares no teste de resolução temporal após a intervenção. Os escores dos testes de qualidade de vida e sintomas depressivos não foram significantemente diferentes entre grupos e avaliações. Conclusão: O uso efetivo de próteses auditivas, associado ou não ao treinamento musical, melhorou a resolução temporal. Não houve melhora significativa na qualidade de vida, sintomas depressivos, cognição e COSI.

Introduction: Association between hearing aid fitting and auditory training can improve an individual's communication and reduce functional deficits. Objective: to verify benefit in quality of life, depressive symptoms, cognitive aspects, temporal resolution, and limitation in daily activities for elderly people with hearing loss, after adaptation of hearing aids associated or not with musical auditory training. Methods: Experimental Group - EG: five elderly (64 to 79 years old) and Control Group - CG: five elderly (62 to 77 years old), all with moderate symmetric sensorineural hearing loss. They underwent anamnesis, cognitive screening CASI-S, audiological evaluation including Percentage Index of Speech Recognition (PISR), Client-Oriented Scale of Improvement (COSI), temporal resolution (GIN), screening for depressive symptoms (GDS-15), quality of life questionnaires (SF-36) and IOI-HA self-assessment. All received hearing aids but only the EG received the auditory musical training. Evaluation performed in three moments: before the fitting of the hearing aids; 11 weeks after their adaptation, with the EG undergoing musical training for seven weeks; and four months later. Results: There was no difference between groups according to age, education, and cognitive screening. All had better thresholds in the GIN after the intervention. The GDS-15 and SF-36 scores were not significantly different between groups and assessments. Conclusion: Using hearing aids associated or not with musical training improved temporal resolution. There was no improvement in the quality of life, depressive symptoms, cognition, and COSI scale.

Introducción: Asociación entre adaptación de prótesis auditivas y entrenamiento auditivo puede mejorar la comunicación del individuo y reducir los déficits funcionales. Objetivo: verificar el beneficio en la calidad de vida, síntomas depresivos, aspectos cognitivos, resolución temporal y limitación de la vida de las personas mayores con hipoacusia, tras adaptación de audífonos asociada o no al entrenamiento auditivo musical. Métodos: Grupo Experimental ­ GE: cinco ancianos (64 a 79 años) y Grupo Control - GC: cinco ancianos (62 a 77 años) todos con hipoacusia neurosensorial simétrica moderada. Fueron sometidos a la anamnesis, miniprueba de triaje cognitiva CASI-S, evaluación audiológica incluyendo Índice Porcentual de Reconocimiento de Habla (IPRH), Client-Oriented Scale of Improvement (COSI), resolución temporal (prueba GIN), classificación para síntomas depresivos (EDG-15), cuestionarios de calidad de vida (SF-36) y autoevaluación de audífonos (QI-AASI). Todos recibieron los audífonos, sólo el GE, el entrenamiento auditivo musical. Evaluación realizada en tres momentos: antes de la adaptación de los audífonos; 11 semanas después de la adaptación de las mismas siendo el GE sometido al entrenamiento musical por siete semanas; y cuatro meses después. Resultados: No hubo diferencia entre grupos según edad, escolaridad y triaje cognitivo. Todos presentaron mejores umbrales en la prueba de resolución temporal después de la intervención. Los resultados de las pruebas de calidad de vida y los síntomas depresivos no fueron significativamente diferentes entre grupos y evaluaciones. Conclusión: Usar audífonos asociados o no con entrenamiento musical mejoró la resolución temporal. No hubo mejora significativa en la calidad de vida, síntomas depresivos, cognición y COSI.

Total GABA level in human auditory cortex is associated with speech-in-noise understanding in older age.

Speech-in-noise (SIN) understanding often becomes difficult for older adults because of impaired hearing and aging-related changes in central auditory processing. Central auditory processing depends on a fine balance between excitatory and inhibitory neural mechanisms, which may be upset in older age by a change in the level of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). In this study, we used MEGA-PRESS magnetic resonance spectroscopy (MRS) to estimate GABA levels in both the left and right auditory cortices of young and older adults. We found that total auditory GABA levels were lower in older compared to young adults. To understand the relationship between GABA and hearing function, we correlated GABA levels with hearing loss and SIN performance. In older adults, the GABA level in the right auditory cortex was correlated with age and SIN performance. The relationship between chronological age and SIN loss was partially mediated by the GABA level in the right auditory cortex. These findings support the hypothesis that inhibitory mechanisms in the auditory system are reduced in aging, and this reduction relates to functional impairments.

Functional organization of mouse primary auditory cortex in adult C57BL/6 and F1 (CBAxC57) mice.

The primary auditory cortex (A1) plays a key role for sound perception since it represents one of the first cortical processing stations for sounds. Recent studies have shown that on the cellular level the frequency organization of A1 is more heterogeneous than previously appreciated. However, many of these studies were performed in mice on the C57BL/6 background which develop high frequency hearing loss with age making them a less optimal choice for auditory research. In contrast, mice on the CBA background retain better hearing sensitivity in old age. Since potential strain differences could exist in A1 organization between strains, we performed comparative analysis of neuronal populations in A1 of adult (~ 10 weeks) C57BL/6 mice and F1 (CBAxC57) mice. We used in vivo 2-photon imaging of pyramidal neurons in cortical layers L4 and L2/3 of awake mouse primary auditory cortex (A1) to characterize the populations of neurons that were active to tonal stimuli. Pure tones recruited neurons of widely ranging frequency preference in both layers and strains with neurons in F1 (CBAxC57) mice exhibiting a wider range of frequency preference particularly to higher frequencies. Frequency selectivity was slightly higher in C57BL/6 mice while neurons in F1 (CBAxC57) mice showed a greater sound-level sensitivity. The spatial heterogeneity of frequency preference was present in both strains with F1 (CBAxC57) mice exhibiting higher tuning diversity across all measured length scales. Our results demonstrate that the tone evoked responses and frequency representation in A1 of adult C57BL/6 and F1 (CBAxC57) mice are largely similar.

Reduced suprathreshold auditory nerve responses are associated with slower processing speed and thinner temporal and parietal cortex in presbycusis.

Epidemiological evidence shows an association between hearing loss and dementia in elderly people. However, the mechanisms that connect hearing impairments and cognitive decline are still unknown. Here we propose that a suprathreshold auditory-nerve impairment is associated with cognitive decline and brain atrophy. METHODS: audiological, neuropsychological, and brain structural 3-Tesla MRI data were obtained from elders with different levels of hearing loss recruited in the ANDES cohort. The amplitude of waves I (auditory nerve) and V (midbrain) from auditory brainstem responses were measured at 80 dB nHL. We also calculated the ratio between wave V and I as a proxy of suprathreshold brainstem function. RESULTS: we included a total of 101 subjects (age: 73.5 ± 5.2 years (mean ± SD), mean education: 9.5 ± 4.2 years, and mean audiogram thresholds (0.5-4 kHz): 25.5 ± 12.0 dB HL). We obtained reliable suprathreshold waves V in all subjects (n = 101), while replicable waves I were obtained in 92 subjects (91.1%). Partial Spearman correlations (corrected by age, gender, education and hearing thresholds) showed that reduced suprathreshold wave I responses were associated with thinner temporal and parietal cortices, and with slower processing speed as evidenced by the Trail-Making Test-A and digit symbol performance. Non-significant correlations were obtained between wave I amplitudes and other cognitive domains. CONCLUSIONS: These results evidence that reduced suprathreshold auditory nerve responses in presbycusis are associated with slower processing speed and brain structural changes in temporal and parietal regions.

Relative contributions of auditory and cognitive functions on speech recognition in quiet and in noise among older adults / Contribuições relativas das funções auditivas e cognitivas no reconhecimento da fala no silêncio e no ruído entre idosos

Abstract Introduction: Hearing acuity, central auditory processing and cognition contribute to the speech recognition difficulty experienced by older adults. Therefore, quantifying the contribution of these factors on speech recognition problem is important in order to formulate a holistic and effective rehabilitation. Objective: To examine the relative contributions of auditory functioning and cognition status to speech recognition in quiet and in noise. Methods: We measured speech recognition in quiet and in composite noise using the Malay Hearing in noise test on 72 native Malay speakers (60-82 years) older adults with normal to mild hearing loss. Auditory function included pure tone audiogram, gaps-in-noise, and dichotic digit tests. Cognitive function was assessed using the Malay Montreal cognitive assessment. Results: Linear regression analyses using backward elimination technique revealed that had the better ear four frequency average (0.5-4 kHz) (4FA), high frequency average and Malay Montreal cognitive assessment attributed to speech perception in quiet (total r2 = 0.499). On the other hand, high frequency average, Malay Montreal cognitive assessment and dichotic digit tests contributed significantly to speech recognition in noise (total r2 = 0.307). Whereas the better ear high frequency average primarily measured the speech recognition in quiet, the speech recognition in noise was mainly measured by cognitive function. Conclusions: These findings highlight the fact that besides hearing sensitivity, cognition plays an important role in speech recognition ability among older adults, especially in noisy environments. Therefore, in addition to hearing aids, rehabilitation, which trains cognition, may have a role in improving speech recognition in noise ability of older adults.

Resumo Introdução: A alteração da acuidade auditiva, do processamento auditivo central e da cognição são fatores que contribuem para a dificuldade de reconhecimento da fala em idosos. Portanto, quantificar a contribuição desses fatores no problema de reconhecimento da fala é importante para a formulação de uma reabilitação holística e efetiva. Objetivo: Examinar as contribuições relativas do funcionamento auditivo e do estado cognitivo para o reconhecimento da fala no silêncio e no ruído. Método: Nós medimos o reconhecimento de fala no silêncio e no ruído composto com o teste Malay hearing in noise test em 72 idosos malaios nativos falantes (60-82 anos) com audição normal a perda auditiva de grau leve. A avaliação da função auditiva incluiu audiograma de tons puros, teste gaps-in-noise e testes dicótico de dígitos. A função cognitiva foi avaliada pelo teste Malay Montreal cognitive assessment. Resultados: Análises de regressão linear com técnicas de eliminação backward na orelha melhor revelaram média de quatro frequências (0,5-4 kHz) (4AF), média de alta frequência e teste Malay Montreal cognitive assessment na orelha melhor, mensurada pela percepção da fala no silêncio (r2 total = 0,499). Por outro lado, a média de alta frequência, Malay Montreal cognitive assessment e o teste dicótico de dígitos contribuíram significativamente para o reconhecimento da fala no ruído (r2 total = 0,307). Enquanto a média de alta frequência da melhor orelha mediu principalmente o reconhecimento da fala no silêncio, o reconhecimento da fala no ruído foi mensurado principalmente pela função cognitiva. Conclusões: Esses achados destacam o fato de que, além da sensibilidade auditiva, a cognição desempenha um papel importante na capacidade de reconhecimento da fala em idosos, principalmente em ambientes ruidosos. Portanto, além de aparelhos auditivos, a reabilitação, que treina a cognição, pode ter um papel na melhoria da capacidade do reconhecimento da fala no ruído entre os idosos.

Relative contributions of auditory and cognitive functions on speech recognition in quiet and in noise among older adults.

INTRODUCTION: Hearing acuity, central auditory processing and cognition contribute to the speech recognition difficulty experienced by older adults. Therefore, quantifying the contribution of these factors on speech recognition problem is important in order to formulate a holistic and effective rehabilitation. OBJECTIVE: To examine the relative contributions of auditory functioning and cognition status to speech recognition in quiet and in noise. METHODS: We measured speech recognition in quiet and in composite noise using the Malay Hearing in noise test on 72 native Malay speakers (60-82 years) older adults with normal to mild hearing loss. Auditory function included pure tone audiogram, gaps-in-noise, and dichotic digit tests. Cognitive function was assessed using the Malay Montreal cognitive assessment. RESULTS: Linear regression analyses using backward elimination technique revealed that had the better ear four frequency average (0.5-4kHz) (4FA), high frequency average and Malay Montreal cognitive assessment attributed to speech perception in quiet (total r2=0.499). On the other hand, high frequency average, Malay Montreal cognitive assessment and dichotic digit tests contributed significantly to speech recognition in noise (total r2=0.307). Whereas the better ear high frequency average primarily measured the speech recognition in quiet, the speech recognition in noise was mainly measured by cognitive function. CONCLUSIONS: These findings highlight the fact that besides hearing sensitivity, cognition plays an important role in speech recognition ability among older adults, especially in noisy environments. Therefore, in addition to hearing aids, rehabilitation, which trains cognition, may have a role in improving speech recognition in noise ability of older adults.

Effects of enriched endogenous omega-3 fatty acids on age-related hearing loss in mice.

OBJECTIVE: Dietary intervention is a practical prevention strategy for age-related hearing loss (AHL). Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) may be effective in prevention of AHL due to their anti-inflammatory and tissue-protective functions. Age-related changes in the hearing function of wild-type and Fat-1 transgenic mice derived from the C57BL/6N strain, which can convert omega-6 PUFAs to n-3 PUFAs and consequently produce enriched endogenous n-3 PUFAs, were investigated to test the efficacy of n-3 PUFAs for AHL prevention. RESULTS: At 2 months, the baseline auditory brainstem response (ABR) thresholds were the same in Fat-1 and wild-type mice at 8-16 kHz but were significantly higher in Fat-1 mice at 4 and 32 kHz. In contrast, the ABR thresholds of Fat-1 mice were significantly lower at 10 months. Moreover, the ABR thresholds of Fat-1 mice at low-middle frequencies were significantly lower at 13 months (12 kHz). Body weights were significantly reduced in Fat-1 mice at 13 months, but not at 2, 10, and 16-17 months. In conclusion, enriched endogenous n-3 PUFAs produced due to the expression of the Fat-1 transgene partially alleviated AHL in male C57BL/6N mice.

Auditory-frontal Channeling in α and ß Bands is Altered by Age-related Hearing Loss and Relates to Speech Perception in Noise.

Difficulty understanding speech-in-noise (SIN) is a pervasive problem faced by older adults particularly those with hearing loss. Previous studies have identified structural and functional changes in the brain that contribute to older adults' speech perception difficulties. Yet, many of these studies use neuroimaging techniques that evaluate only gross activation in isolated brain regions. Neural oscillations may provide further insight into the processes underlying SIN perception as well as the interaction between auditory cortex and prefrontal linguistic brain regions that mediate complex behaviors. We examined frequency-specific neural oscillations and functional connectivity of the EEG in older adults with and without hearing loss during an active SIN perception task. Brain-behavior correlations revealed listeners who were more resistant to the detrimental effects of noise also demonstrated greater modulation of α phase coherence between clean and noise-degraded speech, suggesting α desynchronization reflects release from inhibition and more flexible allocation of neural resources. Additionally, we found top-down ß connectivity between prefrontal and auditory cortices strengthened with poorer hearing thresholds despite minimal behavioral differences. This is consistent with the proposal that linguistic brain areas may be recruited to compensate for impoverished auditory inputs through increased top-down predictions to assist SIN perception. Overall, these results emphasize the importance of top-down signaling in low-frequency brain rhythms that help compensate for hearing-related declines and facilitate efficient SIN processing.

Can Nutritional Intervention for Obesity and Comorbidities Slow Down Age-Related Hearing Impairment?

BACKGROUND: Age-related hearing impairment (ARHI), the most common sensory deficit in the elderly, is associated with enormous social and public health burdens. Emerging evidence has suggested that obesity and comorbidities might increase the risk of ARHI. However, no reviews have been published that address the role of nutritional interventions for obesity and comorbidities in the prevention of ARHI. METHODS: A PubMed database search was conducted to identify the relationship between obesity and ARHI. "Obesity", "metabolic syndrome", "adipose-derived hormone", "fatty acid", and "age-related hearing impairment" were included as keywords. RESULTS: A total of 89 articles was analyzed with 39 articles of relevance to ARHI. A high-fat diet may induce oxidative stress, mitochondrial damage, and apoptosis in the inner ear. Statins have been shown to delay the progression of ARHI by improving the lipid profile, reducing oxidative stress, and inhibiting endothelial inflammation. Aldosterone could exert protective effects against ARHI by upregulating the Na-K-2Cl co-transporter 1 in the cochlea. Omega-3 polyunsaturated fatty acids could preserve the cochlear microcirculation by reducing dyslipidemia and inhibiting inflammation. Alpha-lipoic acid and lecithin might delay the progression of ARHI by protecting cochlear mitochondrial DNA from damage due to oxidative stress. Tea and ginseng might protect against ARHI through their anti-obesity and anti-diabetic effects. CONCLUSIONS: Nutritional interventions for obesity and comorbidities, including a low-fat diet, supplementation with statins, aldosterone, omega-3 polyunsaturated fatty acids, alpha-lipoic acids, lecithin, tea, and ginseng, may protect against the development of ARHI.

Auditory Evoked Responses in Older Adults With Normal Hearing, Untreated, and Treated Age-Related Hearing Loss.

OBJECTIVES: The goal of this study was to identify the effects of auditory deprivation (age-related hearing loss) and auditory stimulation (history of hearing aid use) on the neural registration of sound across two stimulus presentation conditions: (1) equal sound pressure level and (2) equal sensation level. DESIGN: We used a between-groups design, involving three groups of 14 older adults (n = 42; 62 to 84 years): (1) clinically defined normal hearing (≤25 dB from 250 to 8000 Hz, bilaterally), (2) bilateral mild-moderate/moderately severe sensorineural hearing loss who have never used hearing aids, and (3) bilateral mild-moderate/moderately severe sensorineural hearing loss who have worn bilateral hearing aids for at least the past 2 years. RESULTS: There were significant delays in the auditory P1-N1-P2 complex in older adults with hearing loss compared with their normal hearing peers when using equal sound pressure levels for all participants. However, when the degree and configuration of hearing loss were accounted for through the presentation of equal sensation level stimuli, no latency delays were observed. These results suggest that stimulus audibility modulates P1-N1-P2 morphology and should be controlled for when defining deprivation and stimulus-related neuroplasticity in people with hearing loss. Moreover, a history of auditory stimulation, in the form of hearing aid use, does not appreciably alter the neural registration of unaided auditory evoked brain activity when quantified by the P1-N1-P2. CONCLUSIONS: When comparing auditory cortical responses in older adults with and without hearing loss, stimulus audibility, and not hearing loss-related neurophysiological changes, results in delayed response latency for those with age-related hearing loss. Future studies should carefully consider stimulus presentation levels when drawing conclusions about deprivation- and stimulation-related neuroplasticity. Additionally, auditory stimulation, in the form of a history of hearing aid use, does not significantly affect the neural registration of sound when quantified using the P1-N1-P2-evoked response.

Polyphenols From Grape and Blueberry Improve Episodic Memory in Healthy Elderly with Lower Level of Memory Performance: A Bicentric Double-Blind, Randomized, Placebo-Controlled Clinical Study.

Polyphenols are promising nutritional bioactives exhibiting beneficial effect on age-related cognitive decline. This study evaluated the effect of a polyphenol-rich extract from grape and blueberry (PEGB) on memory of healthy elderly subjects (60-70 years-old). A bicentric, randomized, double-blind, placebo-controlled trial was conducted with 215 volunteers receiving 600 mg/day of PEGB (containing 258 mg flavonoids) or a placebo for 6 months. The primary outcome was the CANTAB Paired Associate Learning (PAL), a visuospatial learning and episodic memory test. Secondary outcomes included verbal episodic and recognition memory (VRM) and working memory (SSP). There was no significant effect of PEGB on the PAL on the whole cohort. Yet, PEGB supplementation improved VRM-free recall. Stratifying the cohort in quartiles based on PAL at baseline revealed a subgroup with advanced cognitive decline (decliners) who responded positively to the PEGB. In this group, PEGB consumption was also associated with a better VRM-delayed recognition. In addition to a lower polyphenol consumption, the urine metabolomic profile of decliners revealed that they excreted more metabolites. Urinary concentrations of specific flavan-3-ols metabolites were associated, at the end of the intervention, with the memory improvements. Our study demonstrates that PEGB improves age-related episodic memory decline in individuals with the highest cognitive impairments.

Cognitive Function Prediction of Performance During Dual-Tasks Across Adults With and Without Hearing Loss.

BACKGROUND: Dual-task procedures are commonly implemented to examine cognitive load and listening effort as individual differences in cognition often determine successful listening. However, which methods are most efficacious is unclear. Specifically, standardized, targeted assessment procedures for establishing cognitive function, and age-related changes that might account for changes in dual-task performance have yet to be established. Additional data are needed across aging populations, including middle-aged adults and older adults to establish the trend of performance changes throughout the aging process. Investigations of the relationship between cognitive function and dual-task performance may better inform clinical decisions. OBJECTIVE: The purpose of this study was to investigate if cognitive function predicts dual-task performance across adults with and without hearing loss. METHODS: Participants were divided into two groups based on age. Group 1: 14 listeners (Female = 11), 30-50 years old, with normal hearing. Group 2: 12 listeners (Female = 9), 60-80 years old, with normal hearing to near-normal hearing, including typical age-related hearing loss. Participants were administered four of the Woodcock-Johnson III cognitive subtests and standard hearing threshold procedures. All participants were tested in each of three experimental conditions, including two perceptual-cognitive dual-tasks: (1) Auditory word recognition + visual processing, (2) Auditory working memory (sentence) + visual processing in noise, and (3) Auditory working memory (word) + visual processing. RESULTS: Results indicated that cognitive function does predict dual-task performance regardless of age and hearing function. CONCLUSION: Cognitive function may predict dual-task performance during speech-in-noise tasks. Further research investigating the predictive value of related cognitive subtests to listening effort is warranted.

Polyphenols protect against age-associated apoptosis in female rat cochleae.

Dietary antioxidants, polyphenols, have been found to be beneficial in protecting against the generation of oxidative stress in various diseases associated with aging. Age-related hearing loss (AHL) is the number one neurodegenerative disorder on our aged population. Sprague-Dawley rats divided into five groups according to their age (3, 6, 12, 18 and 24 months old) and treated with 100 mg/day/kg body weight of polyphenols were used. Then, cochleae were harvested to measure caspase activities (- 3, - 8 and - 9), caspase-3 gene expression, ATP levels, Bax, BcL-2 and p53 levels. 8-OHdG levels (marker of DNA oxidative damage) and annexin-V were also measured in cochleae. Increased levels of caspase-3 and 9 in cochlea were observed with age and this effect was attenuated by polyphenol treatment. In addition, ATP and Bcl-2 levels in older rats were recovered after administration of polyphenols, while Bax and p53 levels protein decreased. Oral supplementation with polyphenols also reduces DNA oxidative damage of cochlear cell. Treatment with polyphenols inhibits the activation of age-related apoptotic signaling by decreasing oxidative stress inside the rat cochlea.

A Novel Communication Value Task Demonstrates Evidence of Response Bias in Cases with Presbyacusis.

Decision-making about the expected value of an experience or behavior can explain hearing health behaviors in older adults with hearing loss. Forty-four middle-aged to older adults (68.45 ± 7.73 years) performed a task in which they were asked to decide whether information from a surgeon or an administrative assistant would be important to their health in hypothetical communication scenarios across visual signal-to-noise ratios (SNR). Participants also could choose to view the briefly presented sentences multiple times. The number of these effortful attempts to read the stimuli served as a measure of demand for information to make a health importance decision. Participants with poorer high frequency hearing more frequently decided that information was important to their health compared to participants with better high frequency hearing. This appeared to reflect a response bias because participants with high frequency hearing loss demonstrated shorter response latencies when they rated the sentences as important to their health. However, elevated high frequency hearing thresholds did not predict demand for information to make a health importance decision. The results highlight the utility of a performance-based measure to characterize effort and expected value from performing tasks in older adults with hearing loss.

[Effect of Electroacupuncture on Expression of Catechol-O-methyltransferase in the Inferior Colliculus and Auditory Cortex in Age-related Hearing Loss Guinea Pigs].

OBJECTIVE: To observe the expression of catechol-O-methyltransferase (COMT) in inferior colliculus and auditory cortex of guinea pigs with age-related hearing loss(AHL) induced by D-galactose, so as to explore the possible mechanism of electroacupuncture(EA) underlying preventing AHL. METHODS: Thirty 3-month-old guinea pigs were randomly divided into control group, model group and EA group(n=10 in each group), and ten 18-month-old guinea pigs were allocated as elderly group. The AHL model was established by subcutaneous injection of D-galactose. EA was applied to bilateral "Yifeng"(SJ 17) and "Tinggong"(SI 19) for 15 min in the EA group while modeling, once daily for 6 weeks. After treatment, the latency of auditory brainstem response(ABR) Ⅲ wave was measured by a brain-stem evoked potentiometer. The expressions of COMT in the inferior colliculus and auditory cortex were detected by Western blot. RESULTS: Compared with the control group, the latencies of ABR Ⅲ wave were significantly prolonged and the expressions of COMT in the inferior colliculus and auditory cortex were significantly decreased in the model group and the elderly group(P<0.05). After the treatment, the latency of ABR Ⅲ wave was significantly shortened and the expressions of COMT in the inferior colliculus and auditory cortex were significantly increased in the EA group in comparison with the model group (P<0.05). CONCLUSIONS: EA at "Yifeng" (SJ 17) and "Tinggong" (SI 19) can improve the hearing of age-related deafness in guinea pigs, which may contribute to its effect in up-regulating the expression of COMT in the inferior colliculus and auditory cortex.

A nonsynonymous mutation in the WFS1 gene in a Finnish family with age-related hearing impairment.

Wolfram syndrome (WS) is caused by recessive mutations in the Wolfram syndrome 1 (WFS1) gene. Sensorineural hearing impairment (HI) is a frequent feature in WS and, furthermore, certain mutations in WFS1 cause nonsyndromic dominantly inherited low-frequency sensorineural HI. These two phenotypes are clinically distinct indicating that WFS1 is a reasonable candidate for genetic studies in patients with other phenotypes of HI. Here we have investigated, whether the variation in WFS1 has a pathogenic role in age-related hearing impairment (ARHI). WFS1 gene was investigated in a population sample of 518 Finnish adults born in 1938-1949 and representing variable hearing phenotypes. Identified variants were evaluated with respect to pathogenic potential. A rare mutation predicted to be pathogenic was found in a family with many members with impaired hearing. Twenty members were recruited to a segregation study and a detailed clinical examination. Heterozygous p.Tyr528His variant segregated completely with late-onset HI in which hearing deteriorated first at high frequencies and progressed to mid and low frequencies later in life. We report the first mutation in the WFS1 gene causing late-onset HI with audiogram configurations typical for ARHI. Monogenic forms of ARHI are rare and our results add WFS1 to the short list of such genes.