Clinical manifestations

Presentation and course

Patients with presbycusis develop an insidiously progressive bilateral sensorineural hearing loss, which becomes functionally problematic in late life. The main presenting symptoms are hearing loss (about 50%), subjective tinnitus (about 25%), or both (about 25%) (77). Presbycusis is generally considered to be fairly symmetric, but the “oldest old” (ie, > 95 years) commonly demonstrate asymmetric hearing thresholds and word recognitions scores that are not indicative of retrocochlear pathology (62).

Patients affected by presbycusis find the speech of others to sound mumbled or muffled, and have particular difficulty perceiving or discriminating high-pitched consonants (eg, ch, f, k, s, t, or th) compared to lower-pitched vowel sounds (17). They have more difficulty hearing the higher-pitched voices of women and children than men’s voices, and they typically have difficulty understanding conversations when there is background noise. Some sounds may be distorted or perceived as overly loud: when talking at a regular pitch and volume, the patient may have difficulty discriminating speech sounds, whereas compensatory efforts by the speaker to talk in a lower register and more loudly can produce an irritated response from the patient (“You don’t have to yell!”). Presbycusis is often associated with subjective tinnitus, which has been called "presbytinnitus" in this circumstance. However, there is no significant association between the hearing loss of patients with presbycusis and the pitch and loudness of the associated subjective tinnitus (91).

Although there is insufficient evidence to confirm the existence of "central" presbycusis as an isolated entity (53), central auditory dysfunction (ie, involving the auditory pathways in the brain) is nevertheless an important component of presbycusis that may contribute to clinical communication difficulties to varying degrees. Measures of central auditory function may decline more quickly with age than measures of peripheral auditory function (38). Central presbycusis is characterized by marked difficulty hearing in noise, a problem that is not ameliorated—and indeed may be exacerbated—by amplification (36). Individuals with central presbycusis also have difficulty with various behavioral measures: speech in competition, temporally distorted speech, and binaural speech perception (especially dichotic listening) (53).

Patients with presbycusis have impaired ability to recognize facial emotional reactions (09). Facial emotional recognition impairment in presbycusis is associated with atrophy of neural structures engaged in the perceptual and conceptual level of face emotion processing: the right insula, right hippocampus, bilateral cingulate cortex, and multiple areas of the temporal cortex (09).

Presbycusis is stigmatizing (23; 101). Patients with presbycusis experience all three of the core dimensions of stigma, which include cognitive attribution, emotional reactions, and behavioral reactions: (1) cognitive attributions include beliefs that they appear old, stupid, and crippled; (2) emotional reactions include feelings of shame and self-pity as well as feeling that they are being ridiculed; and (3) behavioral reactions include concealment and distancing (23). Hearing devices have a significant positive influence on stigmatic experiences in some patients with presbycusis (23) but in others the hearing devices themselves add to the perceived stigma (101). Indeed, stigma is a prominent barrier to use of hearing aids for some patients, even though modern devices offer in-the-canal models, miniature sizes, and camouflage with hair or skin color (101).

Presbycusis contributes to communication difficulties, isolation, and cognitive decline in elderly adults (93).

Prognosis and complications

Hearing loss can negatively impact the quality of life of affected individuals (20; 101). By impairing communication, hearing loss contributes to loneliness, isolation, dependence, and frustration (39; 20; 21; 101). Furthermore, the increasing cognitive demand of verbal communication and the diminished sense of social connectedness resulting from hearing loss can contribute to feelings of vulnerability and poor health, particularly in the elderly (21). Hearing loss certainly complicates assessment of cognitive function (39), and, in elderly individuals with cognitive impairment or dementia, the added communication difficulty resulting from hearing loss can exacerbate the cognitive dysfunction and also contribute to paranoia.

Biological basis

Etiology and pathogenesis

Presbycusis is a complex disease with multifactorial etiology that results from accumulated damage to the inner ear (and to a lesser degree the central auditory pathways) with aging. The primary pathology involves the hair cells, stria vascularis, and afferent spiral ganglion neurons (31). The underlying pathophysiology of presbycusis involves an interplay between environmental and genetic factors (ie, a gene-environment interaction) (97).

Presbycusis leads to lower activation of the auditory cortices, compared to the elderly with normal hearing (35). Age-related hearing loss has a negative effect on advanced auditory processing capabilities and, in particular, accelerates the decline in speech comprehension, especially in speech competition situations (52); as a result, older adults with age-related hearing loss exhibit decompensation of network connections involving multisensory integration (52).

The neural abnormalities in presbycusis subjects with cochlear amplifier dysfunction extend beyond the core auditory network and are associated with cognitive decline in multiple domains (10). For example, one study of patients with presbycusis and cochlear amplifier dysfunction found greater brain atrophy in the cingulate cortex and in the parahippocampus in these patients compared with controls (10), whereas another study noted decreased directed functional connections of the hippocampus in patients with presbycusis (16). In a cross-sectional analysis of 98 participants in a cohort study of hearing and brain biomarkers of Alzheimer disease, early audiometric age-related hearing loss was associated with higher β-amyloid burden measured in vivo with PET scans (42).

Based on the results of resting-state functional magnetic resonance imaging, presbycusis patients develop topological reorganization of the whole-brain functional network, and presbycusis patients with cognitive decline show more obvious changes in these topological properties than those without cognitive decline (45).

Environmental noise exposure and solvent exposure are significant contributors to sensory presbycusis (24), although some reports question the magnitude of the contribution from noise exposure (19). Low-frequency hearing loss is considered typical of strial or “metabolic” presbycusis, and this type of presbycusis is associated with comorbid cardiovascular disease, especially in women (37).

Various medical comorbidities can contribute to age-associated changes in hearing. For example, with diabetes, hyperglycemia and oxidative stress may contribute to cochlear microangiopathy and auditory neuropathy (50).

In addition to changes in the cochlea, presbycusis involves biological aging in the central auditory system (34; 43; 51; 53; 60; 88; 71). Anatomical reductions in neurons of the cochlear nucleus and their output pathways in the elderly can potentially occur due to either primary aging changes in the brain, or to secondary age-dependent plasticity of the cochlear nucleus in response to the age-related loss of inputs from the cochlea (34). Neurophysiological and biochemical studies suggest declines in glycine-mediated inhibition, reflected in increased firing rates in cochlear nucleus neurons, of aging individuals (34). Animal studies indicate that the loss of auditory sensitivity from inner hair cell synaptopathy can be centrally compensated until advanced age (71). In older adults, the GABA level in the right auditory cortex (MEGA-PRESS magnetic resonance spectroscopy) is associated with age and speech-in-noise performance (25).

Age-related declined in auditory function are accompanied by similar age-related declines in vestibular function (04).

Oxidative stress causes profound alterations of various biological structures, including cellular membranes, lipids, proteins, and nucleic acids. Dietary intake of vitamin C is associated with better hearing in the elderly population (56), whereas chronic inflammation is associated with a worsening of presbycusis (102). The cumulative effect of oxidative stress may induce damage to macromolecules such as mitochondrial DNA with the resulting accumulation of mutations and an associated decline of mitochondrial function, and secondary induction of apoptosis of the cochlear cells (107). Reduced glutathione (GSH) is one of the most important scavengers of reactive oxygen species, and its ratio with oxidized glutathione (GSSG) is a marker of oxidative stress; high glutathione peroxidase activity with a low GSH:GSSG ratio is a risk factor for presbycusis, suggesting that oxidative stress contributes to presbycusis (49).

Genetic factors predispose affected individuals to develop hearing loss with advancing age (32; 83; 07; 13; 03; 27; 67; 48; 11; 57; 82). One proposed mechanism for presbycusis is a significant increase in oxidative stress in the cochlea, and indeed polymorphisms of several antioxidant enzymes that have been linked to presbycusis, including polymorphisms of the enzymes glutathione S-transferase (GST), N-acetyltransferase (NAT), and cytochrome P450 1A1 (CYP1A1) (07; 03; 67). Common alleles of GRM7, the gene encoding metabotropic glutamate receptor type 7, also contribute to an individual's risk of developing presbycusis, possibly through a mechanism of altered susceptibility to glutamate excitotoxicity in hair cells and in spiral ganglion cells of the inner ear where the gene is expressed (32). Using microarray analysis to identify presbycusis-associated genes, a variety of genes involved in immunity and apoptosis are associated with human presbycusis (27). In particular, BAK-mediated apoptosis may be a core mechanism in the progression of age-related hearing loss (30).

Gene polymorphisms in folate metabolism may play an important role in the etiology of presbycusis (66). Various gene polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS) are significantly associated with the onset of presbycusis in a South Indian population (66).

Multiple genes that are known to be expressed in the adult human cochlea are differentially hypermethylated in blood cells among elderly women with presbycusis (12). The significance of this finding is not yet clear. P2RX2, KCNQ5, ERBB3, and SOCS3 are associated with the progression of presbycusis (12).

In addition to chromosomal genetic factors, mutations of mitochondrial DNA are involved in the development of presbycusis (69; 107; 29; 48). In particular, presbycusis is associated with the 4977 bp common deletion (69), which is also known to be increased in aging tissues and is preferentially found in chronologically and photoaged skin. As mentioned above, these mitochondrial mutations may result from the cumulative effect of oxidative stress (107).

Individuals with downward-sloping audiometric patterns of presbycusis exhibit degeneration of the stria vascularis, spiral ganglion cells, inner hair cells, and outer hair cells (75). Sensory (hair cell) presbycusis in particular is characterized by a precipitous high tone loss, ie, the high-frequency steeply sloping pattern (15). Loss of peripheral neurites in the anterior basal cochlear segment is associated with a gradual down-sloping audiogram, ie, the high-frequency gently sloping pattern (15). In contrast, individuals with flat audiometric patterns of presbycusis typically have outer hair cell loss alone or in combination with inner hair cell or ganglion cell loss, but infrequently have stria vascularis atrophy (74).

The presence of subjective tinnitus in patients with presbycusis is associated with more severe degeneration of outer hair cells and stria vascularis (98).

Epidemiology

Presbycusis is the most prevalent sensory impairment in the elderly (13; 20) and the third most prevalent chronic condition in older Americans, after hypertension and arthritis (63). Presbycusis affects about one third of people aged 65 years and older, and up to one half of people aged 75 years and older, although some estimates place the proportion of elderly patients affected much higher (94; 81; 86). However, the prevalence of presbycusis varies with the pure-tone averaged frequencies and the classification system used (86).

Hearing loss progressively worsens with age. In a cross-sectional analysis using the 2005 to 2006, 2009 to 2010, and 2011 to 2012 cycles of the U.S. National Health and Nutrition Examination Survey (NHANES), hearing loss steadily worsened across the adult lifespan to at least age 100 years (92). When cases are limited to those with at least moderately severe hearing loss in the better ear (ie, pure tone average at the speech frequencies of 0.5, 1, and 2 KHz of > 55 dB), the prevalence increases with age, but at more modest levels: in a study among older Chinese people in Taiwan, the prevalence was 1.6% from 65 to 69 years, 3.2% for 70 to 74 years, 7.5% for 75 to 79 years, and 14.9% for those aged 80 and over (14). The rate of hearing loss increases during the tenth decade of life compared with the ninth decade (104).

Presbycusis preferentially affects the high-frequency range of hearing (58). Virtually all centenarians have some degree of presbycusis, and more than 90% suffer from moderate to severe (41 to 80 dB) hearing loss below 2 kHz, and profound (> 81 dB) hearing loss at 4 and 8 kHz (68; 62).

Risk factors for presbycusis include repeated exposure to loud noises (including occupational noise exposure), smoking, certain medications (eg, cancer chemotherapy, particularly with cisplatin; some antibiotics, particularly aminoglycosides; loop diuretics; and aspirin and other anti-inflammatory agents), several comorbid conditions (eg, cardiovascular disease, hypertension, diabetes, and renal failure), and a family history of presbycusis (50; 87; 05). Premature hair graying may be a risk factor for age-associated hearing impairment at extended high frequencies (79). The various risk factors for presbycusis can be grouped into four major categories: (1) aging; (2) environmental (eg, noise exposure); (3) genetic predisposition; and (4) health comorbidities (eg, cigarette smoking and atherosclerosis) (107).

Dietary antioxidants may help reduce the risk of developing presbycusis because higher intake of seeds and nuts, fruits, seaweed, and vitamin A were positively associated with better hearing in a nationwide cross-sectional survey of 5201 older adults (aged 50 years and older) in the fifth Korean National Health and Nutrition Examination Survey from 2010 to 2012 (18).

Hearing loss is associated with a higher incidence of cognitive impairment and dementia in older adults (41; 95; 99; 55; 73). In a 10-year national population-based study, the incidence of dementia was 1.3-fold higher among patients with age-related hearing loss, suggesting that age-related hearing loss may be one of the early characteristics of dementia (95). In another study, observed hearing loss was associated with a 1.7-fold increased risk of developing dementia in a multiethnic cohort (41).

Smoking and diabetes have a strong synergistic effect on presbycusis (05).

In the Rotterdam Study, a longitudinal cohort study of individuals aged greater than or equal to 45 years from a suburb of Rotterdam, the Netherlands, hearing loss among 3590 nondemented community-dwelling participants was associated with lower cognitive function at baseline and accelerated cognitive decline on a memory test (22). However, the association between hearing loss and accelerated cognitive decline was nonsignificant after adjustment for nonlinear age effects. The authors concluded that more evidence is needed to determine if hearing loss is a modifiable risk factor for cognitive decline.

Prevention

Because smoking and diabetes have a strong synergistic effect on presbycusis, patients with diabetes should strictly avoid or cease smoking to prevent the progression of age-related hearing loss (05).

Differential diagnosis

Confusing conditions

Other common causes of sensorineural hearing loss include noise-induced hearing loss, vascular occlusive disease, trauma, Meniere syndrome, viral infections, meningitis, toxins, and genetic syndromes. Less common causes include acoustic neuroma. Distinguishing these various conditions requires attention to past medical and environmental exposure history (eg, noise or toxin exposure, trauma, etc.), onset and course of hearing loss, whether the hearing loss is unilateral or bilateral, the distribution of hearing loss as a function of sound frequency, associated manifestations (eg, subjective tinnitus, vertigo), and family history.

Hearing loss from presbycusis is insidious in onset and gradually progressive. Noise-induced hearing loss has an insidious onset and is either gradually progressive (with continued noise exposure) or static. In contrast, hearing loss associated with vascular occlusive disease, trauma, and viral infections has an acute onset and remains static or may improve. Hearing loss associated with ototoxins or meningitis has a subacute onset and is later static once the cause is removed. Hearing loss associated with Meniere syndrome is fluctuating.

Noise-induced hearing loss is typically bilateral, but may be more severe in one ear, particularly in those using firearms and in professional musicians who play stringed instruments. In contrast, hearing loss associated with many of the other conditions is typically unilateral (eg, vascular occlusive disease, trauma, Meniere syndrome, viral neurolabyrinthitis, acoustic neuroma). Vascular hearing loss may rarely be bilateral with severe vertebrobasilar occlusive disease. Meniere syndrome is generally unilateral at onset, but may progress to bilateral involvement and, in any case, typically is at a much younger age.

The configuration of hearing loss on the audiogram can be helpful in suggesting or supporting an etiology. Conductive hearing loss indicates another disorder or a mixed condition.

A bilaterally symmetric, flat, or downward sloping pattern of sensorineural hearing loss suggests presbycusis, whereas a notched pattern of sensorineural hearing loss with a notch at 4000 or 6000 Hz is suggestive of noise-induced hearing loss (08; 78; 76; 44; 70) and a low-frequency trough pattern suggests Meniere syndrome.

Diagnostic workup

Simple office-based screening and evaluation procedures can identify potential hearing disorders. Screening can be performed periodically by asking the patient or family if there are perceived hearing problems, or by using clinical office tests such as whispered voice, finger rub, and related techniques (100; 80; 103).

Complaints of hearing loss or subjective tinnitus, or positive results from office screening and evaluation procedures, should prompt audiologic referral to confirm the diagnosis with audiometric testing (100; 80; 103). The pure-tone threshold on the pure-tone audiogram is a good predictor of speech perception by speech audiometry among older persons (65).

Management

Remediation of hearing loss is an important contributor to quality of life among elderly persons with presbycusis. Useful management approaches include education about communication effectiveness, hearing aids, assistive listening devices, and cochlear implants for severe hearing loss (39).

Healthcare professionals and family members can improve communication with affected patients by facing the person (so that the impaired person can easily see face and lip movements), speaking in a lower register with short simple sentences, and eliminating extraneous background sounds when possible. Lip reading is an important compensatory strategy for affected individuals and has been shown to improve comprehension (85; 84). Individuals with presbycusis or hearing impairment experience significantly improved spoken-word intelligibility when spoken-word recognition is coupled with speechreading, leading to the suggestion that speechreading may serve as a "third ear" (84).

Hearing aids are the principal form of rehabilitation for presbycusis and can specifically improve communication, reduce hearing handicap, and improve the quality of life for affected individuals (105; 40; 64; 72). Hearing aids are effective for treating mild to moderate hearing loss when the device is appropriately selected and fit for the patient, and the patient is motivated and able to use the device (94). Unfortunately, many older adults have difficulty accepting the need for amplification, and many others become dissatisfied with the performance of hearing aids in a variety of sonic environments (80). Consequently, hearing aids remain underused in the elderly, especially among the “oldest old” (104). Newer digital hearing aids may improve performance, but they are expensive and are not covered by Medicare (80).

Hearing aids are of most benefit for those with sensory presbycusis. Neural and central types of presbycusis are rare and may not exist in strict isolation but are significant because amplification typically does not benefit patients with significant neural or central contributions to their hearing loss (36).

Dementia is another barrier to use of hearing aids. Patients with presbycusis and dementia typically require the cooperation of their caregivers to maintain the hygiene of their ear canals, to maintain and adjust the hearing aids, and to facilitate insertion (54). Nevertheless, it is important for such patients to optimize their hearing to improve their communication with others, maintain and maximize their functional performance, lessen the frequency of problematic neuropsychiatric features (eg, agitation, depression, and paranoia), limit their dependence on others, and lessen their need for institutional care.

Assistive devices (eg, built-in telephone amplifier, low-frequency doorbells, amplified ringers, close-captioned television decoders, flashing alarm clocks, flashing smoke detectors, and alarm bed vibrators) and training in “speech-reading” (ie, using visual cues to help determine what is being said) are helpful for many patients with presbycusis (105; 40). Instruction in sign language should be considered for those with severe hearing loss associated with presbycusis.

For selected patients with profound hearing loss that is not improved by a simple hearing aid, a cochlear implant device may provide functional hearing (39; 94; 21); there is no absolute age threshold beyond when this procedure cannot be done for appropriate patients. Cochlear implantation may improve audiologic performance and quality of life in elderly patients, even into their eighties (59; 39; 28; 94; 61). Among patients treated with cochlear implants for hearing loss, patients with presbycusis perform as well as younger patients on speech discrimination tests in quiet environments, but perform significantly worse in noisy surroundings, possibly due to contributions from central presbycusis (61). Pain and transient vertigo are the most common complications reported in elderly patients following cochlear implantation (28).

A variety of pharmacological agents have been explored for their potential to slow the development of hearing loss, or treat the associated subjective tinnitus, in people with presbycusis (46; 96; 33; 47). To date, none of these agents have an established role in the management of presbycusis, and none have been approved for treatment of presbycusis by the U.S. Food and Drug Administration. However, preliminary data suggest that a water-soluble coenzyme Q10 formulation may be helpful in improving hearing in patients with presbycusis (46). Preliminary data also suggest that pramipexole may improve subjective tinnitus associated with presbycusis, although it does not change hearing thresholds (96).