In this study we found that hearing loss was independently associated with incident all-cause dementia after adjustment for sex, age, race, education, diabetes, smoking, and hypertension, and our findings were robust to multiple sensitivity analyses. The risk of all-cause dementia increased log-linearly with hearing loss severity, and for individuals >60 years in our cohort, over one-third of the risk of incident all-cause dementia was associated with hearing loss.
Our findings contribute significantly to the discussion in the literature on whether hearing loss is a risk factor for dementia. Previous studies suggested that individuals with hearing loss are more likely to have a diagnosis of dementia 5;6
and poorer cognitive function 15
. Supporting this hypothesis, smaller prospective studies have observed that hearing loss is associated with accelerated cognitive decline in individuals with prevalent dementia 16;17
. Although, a prospective study of cognitively-normal elderly volunteers failed to find any meaningful association between hearing loss at study entry and later cognitive function, the results of this study are questionable because of the short (5-year) follow-up and a 50% dropout rate 18
. In our study, hearing loss, a condition that is highly prevalent in older adults and often remains untreated 19
, was strongly and prospectively associated with incident dementia.
A number of mechanisms may be theoretically implicated in the observed association between hearing loss and incident dementia. There may be an over-diagnosis of dementia in individuals affected by hearing loss, or vice versa an over-diagnosis of hearing loss in individuals with cognitive impairment at baseline. An over-diagnosis of dementia in our study is unlikely because the diagnostic protocol for incident dementia relied on a consensus conference that examined information from multiple sources. We also conducted sensitivity analyses censoring individuals diagnosed with dementia during a 6-year washout period from baseline that did not affect our results. In such an analysis, individuals would already have had several “normal” cognitive exams with hearing loss before being diagnosed with dementia, likely making the dementia diagnosis not confounded by poor communication. Hearing loss (short of profound deafness) also minimally impairs face-to-face communication in quiet environments (i.e. during cognitive testing) particularly in the setting of testing by experienced examiners who are accustomed to working with older adults 20
An over-diagnosis of hearing loss is also unlikely since there is no evidence that mild cognitive impairment would affect the reliability of audiometric testing. Behaviorally, pure-tone audiometry has been performed even in children as young as 5 years. We also excluded any individuals with recognized cognitive impairment at baseline (mild cognitive impairment or Blessed > 3), and our results were robust to models controlling for baseline Blessed scores.
Another possibility is that both hearing loss and progressive cognitive impairment are caused by a common neuropathologic process, possibly the same that leads to Alzheimer’s disease. However, pure tone audiometry is typically considered a measure of the auditory periphery because detection of pure tones relies solely on cochlear transduction and neuronal afferents to brainstem nuclei and the primary auditory cortex. Perception of pure tones do not require higher levels of auditory cortical processing 21
, and auditory brainstem response testing of these pathways is usually normal in AD patients 22
. In contrast, central auditory nuclei required for higher order auditory processing can be affected by AD neuropathology 23-25
, and tests of central auditory function have been found to be associated with Alzheimer’s disease 26
The likelihood of another neurobiological process such as vascular disease or factors related to family history (e.g. ApoE status) causing both hearing loss and dementia also cannot be fully excluded. However, risk factors for vascular disease such as diabetes, smoking, and hypertension were adjusted for in our models, and a preliminary study has not found a positive association between ApoE status and hearing hearing loss 27
. Other variables such as mental and leisure activities were not included as covariates in our models since these variables would not be expected to cause hearing loss and act as meaningful confounders in our models. Our results were also robust to excluding individuals at baseline who had a prior history of stroke or TIA.
Finally, hearing loss may be causally related to dementia, possibly through exhaustion of cognitive reserve, social isolation, environmental deafferentation, or a combination of these pathways. Cognitive reserve reflects inter-individual differences in neurocognitive processing that allow some individuals to cope better with neuropathology than others 28
. Functional MRI studies showing inter-individual variation in efficiency of task-related neural processing provide some evidence for this concept 29;30
. Cognitive reserve has also been used to explain discrepancies between the extent of neuropathology seen at autopsy and clinical expression of dementia 31
. The potential effect of hearing loss on cognitive reserve is suggested by studies demonstrating that under conditions where auditory perception is difficult (i.e. hearing loss), greater cognitive resources are dedicated to auditory perceptual processing to the detriment of other cognitive processes such as working memory 32;33
. This reallocation of neural resources to auditory processing could deplete the cognitive reserve available to other cognitive processes and possibly lead to the earlier clinical expression of dementia neuropathology 34
Communication impairments caused by hearing loss can also lead to social isolation in older adults 35;36
, and epidemiologic37;38
and neuroanatomic studies39
have demonstrated associations between poor social networks and dementia. Our results would also seem to support this possible pathway because the risk of dementia associated with hearing loss only appeared to increase at hearing thresholds >25 dB which is considered the threshold at which hearing loss begins to impair verbal communication 40
. Finally, a hypothetical mechanism by which hearing loss could directly affect Alzheimer’s neuropathology is suggested by animal studies demonstrating that environmental enrichment (possibly analogous in humans to having access to auditory and environmental stimuli) can reduce β-amyloid levels in transgenic mouse models 41
. This hypothesis is also supported by studies showing that individuals who remain engaged in leisure activities have a lower risk of dementia 42
In the current study, self-reported hearing aid use was not associated with a significant reduction in dementia risk, but data on other key variables (e.g. type of hearing aid used, hours worn per day, number of years used, characteristics of subjects choosing to use hearing aids, use of other communicative strategies, adequacy of rehabilitation, etc) that would affect the success of aural rehabilitation and affect any observed association were not gathered. Consequently, whether hearing advices and aural rehabilitative strategies could have an effect on cognitive decline and dementia remains unknown and will require further study.
Our study has limitations. First, only the severity of hearing loss at baseline was considered in the analysis, and information was not available on the trajectory of hearing loss after baseline assessment or the possible etiology of the hearing loss . However, it is unlikely that this limitation substantially biased our findings given that reversible hearing loss is rare, and hearing loss tends to only worsen with time. Residual confounding by other environmental, genetic, or neuropathologic processes is also plausible but speculative based on our current knowledge of established risk factors for hearing loss and dementia. Given the very close association between age and both hearing loss and dementia, there is a possibility of unaccounted residual confounding. This is unlikely, however, because we also confirmed our findings in a statistical model using age rather than time-on-study as the time-scale to account for non-linear effects of age on hearing and cognition 43
. Our findings were also unchanged after restricting our cohort to participants ≥65 years at baseline.
Finally, caution must be applied when generalizing the results of our current study because the BLSA is a volunteer cohort of subjects of high socioceconomic status. Further confirmation of our results will need to be performed in larger studies using more representative, community-based samples. This potential limitation to broad generalizability, however, could strengthen the internal validity of our findings given the relative homogeneity of the study cohort in both observed and likely unobservable characteristics.
If confirmed in other independent cohorts the findings of our study could potentially have substantial implications for individuals and public health. Hearing loss in older adults may be preventable 44
and can be practically addressed with current technology (digital hearing aids, cochlear implants) and with other rehabilitative interventions focused on optimizing social and environmental conditions for hearing. With the increasing number of people with hearing loss, research into the mechanistic pathways linking hearing loss with dementia and the potential of rehabilitative strategies to moderate this association are critically needed.