Hidden Age-Related Hearing Loss and Hearing Disorders: Current Knowledge and Future Directions

Abstract

Age-related hearing loss, which affects roughly 35% of those over the age of 70, is the second most common disorder among the elderly. The severity of age related hearing loss may actually be worse if assessments are made under more realistic conditions, such as communicating in noise. Emerging data from humans and animal models suggest that damage to the inner hair cells and/or type I neurons, that relay sound information to the brain may contribute to hearing deficits in a noisy background. Data obtained from carboplatin-treated chinchillas suggest that tone-in-noise thresholds are a sensitive and frequency dependent method of detecting damage to the IHC/type I system. Therefore, tone detection thresholds measured in broadband noise may provide an efficient method of detecting the deficits in specific frequency regions. Preliminary data obtained in elderly subject with normal thresholds in quiet compared to young subjects illustrate the importance of repeating these measurements in broadband noise because thresholds in noise were worse for our elderly subjects than young subjects, even though both groups had similar hearing thresholds in quiet. N-acetyl cysteine supplementation which protects against inner hair cell loss in animal models, may represent a viable therapy for protecting the inner hair cell/type I neurons.

Keywords: Age-related hearing loss; clinical audiogram; hearing disorders; hidden hearing loss; inner hair cells; presbycusis.

Figure 1:

Prevalence of Speech-Frequency and High-Frequency, bilateral hearing impairment in United States women and men from US National Health and Nutrition Examination Survey, 2011–2012. Bilateral impairment defined as pure tone average in both ears > 25 dB HL. Data replotted from Table 1 of Hoffman et al. (4).

Figure 2:

Mean (+/−SEM) audiogram from 10 young females and 10 young males ages 20–27. Mean thresholds in the 0.25–8 kHz range of the clinical audiogram (shaded region) were clinically normal (<25 dB HL) for both males and females. Although male thresholds were slightly higher than females, the gender differences were not significantly different. However, thresholds in the extended high frequency range (10–16 kHz) increased with frequency in males and exceeded the 25 dB HL cutoff for normal at 14 and 16 kHz. Male thresholds were significantly higher than females at 12.5 kHz (p<0.01), 14 kHz (p<0.001) and 16 kHz (p<0.001).

Figure 3:

(A) Photomicrographs of a surface preparation of the chinchilla organ of Corti stained with succinate dehydrogenase, a metabolic enzyme highly expressed in OHC and IHC. Control (upper panel) shows strong staining of all OHC and IHC. When chinchillas were treated with carboplatin, large patches of IHC were missing interspersed among surviving IHC (lower panel); all the OHC by contrast were present. (B) Schematic cochleogram from a carboplatin treated chinchilla in which 60–70% of the IHC were missing from the apex (0%) toward the base of the cochlear (100%); there was virtually no loss of OHC. (C) Schematic showing the thresholds of a typical chinchilla pre- and post-carboplatin treatment that resulted in selective loss of roughly 50% of the IHC. Post-carboplatin treated thresholds were nearly identical to those measured pre-carboplatin. In this example, the large IHC lesion had minimal effect on threshold. (D) Schematic illustrating the change in threshold (i.e., threshold shift) plotted as a function of % IHC loss. Threshold shifts were minimal until the IHC lesion exceeded 75% after which thresholds increased precipitously. Data schematized from Salvi et al. (23).

Figure 4:

Schematic illustrating chinchilla behavioral threshold obtained in the presence of 50 dB SPL broadband noise (BBN) with a spectrum level of ~7 dB SPL/Hz. Prior to carboplatin treatment, behavioral thresholds measured in BBN increased from approximately 30 dB at low frequency to roughly 40 dB at 8–16 kHz. After carboplatin treatment that induced a moderate IHC lesion along the length of the cochlea, the behavioral thresholds in BBN increased roughly 8–10 dB. Data schematized from Lobarinas et al. (31).

Figure 5:

Clinical audiograms in which hearing thresholds in dB HL were measured in quiet from 0.125 to 8 kHz. Shaded areas define range of clinically normal thresholds (<25 dB HL). Mean thresholds (+/− SD) shown for 10 young subjects and six, elderly subjects.

Figure 6:

Tone thresholds as a function of frequency in broadband background noise of (A) 20 dB HL and (B) 30 dB HL. Mean +/− 95% confidence interval shown for 10 young normal hearing subject s (mean age 20.09 years). Means for young subjects increased from 20 dB HL to 30 dB HL noises. Symbols show data for each of six elderly (mean age 62.66 years) subjects (O2-O7) in the 20 and 30 dB HL noise. Most of tone-in-noise thresholds for the elderly subjects were above the mean thresholds of the young subjects for the 20 and 30 dB HL noise conditions; these differences were most pronounced from 2–8 kHz. Little difference observed between the old and young at 1 kHz.

Figure 7:

Cochleograms showing the percent outer hair cell (OHC) and inner hair cell (IHC) loss as a function of percent distance from the apex of the cochlea in CBA and C57BL/6 mice at 8 months and 26 months of age. Frequency vs. place map shown on lower x-axis. Data schematized from Spongr et al. (19).

Figure 8:

Cochleograms showing the percent IHC loss as a function of percent distance from the apex of the cochlear. Lower x-axis shows the relationship between frequency and cochlear place. (A) % IHC loss in dwg/dwg mice at 1, 3, 6 and 9 months of age. (B) % IHC loss at 6 months of age in dwg/dwg control mice and dwg/dwg mice treated with N-acetyl cysteine from 3 weeks to 6 months of age. Data schematized from Ding et al. (62).