Age-related hearing loss is associated with cognitive decline and has been proposed as a risk factor for dementia. However, the mechanisms that relate hearing loss to cognitive decline remain elusive. Here, we propose that the impairment of the cochlear amplifier mechanism is associated with structural brain changes and cognitive impairment. Ninety-six subjects aged over 65 years old (63 female and 33 male) were evaluated using brain magnetic resonance imaging, neuropsychological and audiological assessments, including distortion product otoacoustic emissions as a measure of the cochlear amplifier function. All the analyses were adjusted by age, gender and education. The group with cochlear amplifier dysfunction showed greater brain atrophy in the cingulate cortex and in the parahippocampus. In addition, the atrophy of the cingulate cortex was associated with cognitive impairment in episodic and working memories and in language and visuoconstructive abilities. We conclude that the neural abnormalities observed in presbycusis subjects with cochlear amplifier dysfunction extend beyond core auditory network and are associated with cognitive decline in multiple domains. These results suggest that a cochlear amplifier dysfunction in presbycusis is an important mechanism relating hearing impairments to brain atrophy in the extended network of effortful hearing.

Belkhiria et al. Neurobehavioral Impairment in Presbycusis that (i) the neuropsychiatric symptoms had a major effect on functional loss in subjects with presbycusis, (ii) cochlear dysfunction is relevant for the association between hearing loss and behavioral impairment, and (iii) atrophy of the insula and amygdala among other temporal areas are related with hearing loss and behavioral impairment.

Top-down modulation of sensory responses to distracting stimuli by selective attention has been proposed as an important mechanism by which our brain can maintain relevant information during working memory tasks. Previous works in visual working memory (VWM) have reported modulation of neural responses to distracting sounds at different levels of the central auditory pathways. Whether these modulations occur also at the level of the auditory receptor is unknown. Here, we hypothesize that cochlear responses to irrelevant auditory stimuli can be modulated by the medial olivocochlear system during VWM. Twenty-one subjects (thirteen males, mean age 25.3 years) with normal hearing performed a visual change detection task with different VWM load conditions (high load= 4 visual objects; low load= 2 visual objects). Auditory stimuli were presented as distractors and allowed the measurement of distortion product otoacoustic emissions (DPOAE) and scalp auditory evoked potentials. In addition, the medial olivocochlear reflex strength was evaluated by adding contralateral acoustic stimulation. We found larger contralateral acoustic suppression of DPOAEs during the visual working memory period (n=21) compared to control experiments (n=10), in which individuals were passively exposed to the same experimental conditions. These results show that during the visual working memory period there is a modulation of the medial olivocochlear reflex strength, suggesting a possible common mechanism for top-down filtering of auditory responses during cognitive processes.

25Age-related hearing loss is associated with cognitive decline and has been proposed as a 26 risk factor for dementia. However, the mechanisms that relate hearing loss to cognitive decline 27 remain elusive. Here, we propose that the impairment of the cochlear amplifier mechanism is 28 associated with structural brain changes and cognitive impairment. Ninety-six subjects aged over 29 65 years old (63 female and 33 male) were evaluated using brain magnetic resonance imaging, 30 neuropsychological and audiological assessments, including distortion product otoacoustic 31 emissions as a measure of the cochlear amplifier function. All the analyses were adjusted by age, 32 gender and education. The group with cochlear amplifier dysfunction showed greater brain atrophy 33 in the cingulate cortex and in the parahippocampus. In addition, the atrophy of the cingulate cortex 34 was associated with cognitive impairment in episodic and working memories and in language and 35 visuoconstructive abilities. We conclude that the neural abnormalities observed in presbycusis 36 subjects with cochlear amplifier dysfunction extend beyond core auditory network and are 37 associated with cognitive decline in multiple domains. These results suggest that a cochlear 38 amplifier dysfunction in presbycusis is an important mechanism relating hearing impairments to 39 brain atrophy in the extended network of effortful hearing. 40 41 hearing loss or presbycusis is characterized by bilateral progressive hearing 56 loss and impaired speech understanding, especially in noisy environments (Gates and Mills, 2005). 57According to recent epidemiological data from the US more than 50% of people aged over 70 years 58 have presbycusis (Goman and Lin, 2016), while due to population aging, it is expected that by the 59 year 2025 there will be more than one billion people with hearing loss in the world (Sprinzl and 60 Riechelmann, 2010). The increasing number of hearing loss patients is alarming, since 61 epidemiological evidence has shown an association between presbycusis and cognitive decline in 62 elderly people (Lin and Albert, 2014; Thomson et al., 2017). For instance, Lin et al. (2011) have 63 shown that individuals with mild to moderate presbycusis have worse results in executive function 64 and psychomotor processing, while other studies have shown that hearing loss is significantly 65 related to global cognitive decline, which can lead to social isolation and depression (Harrison 66 Bush et al., 2015; Panza et al., 2015). Furthermore, a recent prospective cohort has reported that 67 presbycusis subjects with audiometric hearing thresholds worse than 40 dB are more likely to 68 develop dementia (Deal et al., 2017). In line with this evidence, a Lancet consortium recently 69 proposed a model in which hearing loss is the major potentially preventable risk factor for dementia 70 (Livingston et al., 2017). 71 72 Although epidemiological and clinical studies confirm the relationship between hearing 73 loss and cognitive decline, the mechanism...

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.

Presbycusis or age-related hearing loss is a prevalent condition in the elderly population, which affects oral communication, especially in background noise, and has been associated with social isolation, depression, and cognitive decline. However, the mechanisms that relate hearing loss with cognition are complex and still elusive. Importantly, recent studies show that the use of hearing aids in presbycusis, which is its standard management, can induce neuroplasticity and modify performance in cognitive tests. As the majority of the previous studies on audition and cognition obtained their results from a mixed sample of subjects, including presbycusis individuals fitted and not fitted with hearing aids, here, we revisited the associations between hearing loss and cognition in a controlled sample of unaided presbycusis. We performed a cross-sectional study in 116 non-demented Chilean volunteers aged ≥65 years from the Auditory and Dementia study cohort. Specifically, we explored associations between bilateral sensorineural hearing loss, suprathreshold auditory brain stem responses, auditory processing (AP), and cognition with a comprehensive neuropsychological examination. The AP assessment included speech perception in noise (SIN), dichotic listening (dichotic digits and staggered spondaic words), and temporal processing [frequency pattern (FP) and gap-in-noise detection]. The neuropsychological evaluations included attention, memory, language, processing speed, executive function, and visuospatial abilities. We performed an exploratory factor analysis that yielded four composite factors, namely, hearing loss, auditory nerve, midbrain, and cognition. These four factors were used for generalized multiple linear regression models. We found significant models showing that hearing loss is associated with bilateral SIN performance, while dichotic listening was associated with cognition. We concluded that the comprehension of the auditory message in unaided presbycusis is a complex process that relies on audition and cognition. In unaided presbycusis with mild hearing loss (<40 dB HL), speech perception of monosyllabic words in background noise is associated with hearing levels, while cognition is associated with dichotic listening and FP.

7Epidemiological evidence shows an association between hearing loss and dementia 3 8 in elderly people. However, the mechanisms that connect hearing impairments and 3 9 cognitive decline are still unknown. Here we propose that a suprathreshold auditory-nerve 4 0 impairment is associated with cognitive decline and brain atrophy. Methods: audiological, 4 1 neuropsychological, and brain structural 3-Tesla MRI data were obtained from elders with 4 2 different levels of hearing loss recruited in the ANDES cohort. The amplitude of waves I 4 3 (auditory nerve) and V (midbrain) from auditory brainstem responses were measured at 80 4 4 dB nHL. We also calculated the ratio between wave V and I as a proxy of a suprathreshold 4 5 brainstem function. Results: we included a total of 101 subjects (age: 73.5 ± 5.2 years 4 6 (mean ± SD), mean education: 9.5 ± 4.2 years, and mean audiogram thresholds (0.5-4 4 7 kHz): 25.5 ± 12.0 dB HL). We obtained reliable suprathreshold waves V in all subjects 4 8

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