Abstract:The association between hearing impairment and dementia has emerged as a major public health challenge, with significant opportunities for earlier diagnosis, treatment and prevention. However, the nature of this association has not been defined. We hear with our brains, particularly within the complex soundscapes of everyday life: neurodegenerative pathologies target the auditory brain, and are therefore predicted to damage hearing function early and profoundly. Here we present evidence for this proposition, b… Show more
“…alpha-synuclein ( SNCA ) 35 or beta-secretase ( BACE1 ) 36 , are also involved in neurodegenerative disorders including AD. This could reinforce the proposal of hearing loss as an interplay of 'peripheral' and 'central' hearing dysfunction, which is linked to cognitive decline and has been attributed increasingly a modifiable risk factor for AD 37 . Figure 3 Unique meaningful GO clusters specific for AD brain.…”
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with typical neuropathological hallmarks, such as neuritic plaques and neurofibrillary tangles, preferentially found at layers III and V. The distribution of both hallmarks provides the basis for the staging of AD, following a hierarchical pattern throughout the cerebral cortex. To unravel the background of this layer-specific vulnerability, we evaluated differential gene expression of supragranular and infragranular layers and subcortical white matter in both healthy controls and AD patients. We identified AD-associated layer-specific differences involving protein-coding and non-coding sequences, most of those present in the subcortical white matter, thus indicating a critical role for long axons and oligodendrocytes in AD pathomechanism. In addition, GO analysis identified networks containing synaptic vesicle transport, vesicle exocytosis and regulation of neurotransmitter levels. Numerous AD-associated layer-specifically expressed genes were previously reported to undergo layer-specific switches in recent hominid brain evolution between layers V and III, i.e., those layers that are most vulnerable to AD pathology. Against the background of our previous finding of accelerated evolution of AD-specific gene expression, here we suggest a critical role in AD pathomechanism for this phylogenetic layer-specific adaptation of gene expression, which is most prominently seen in the white matter compartment.
“…alpha-synuclein ( SNCA ) 35 or beta-secretase ( BACE1 ) 36 , are also involved in neurodegenerative disorders including AD. This could reinforce the proposal of hearing loss as an interplay of 'peripheral' and 'central' hearing dysfunction, which is linked to cognitive decline and has been attributed increasingly a modifiable risk factor for AD 37 . Figure 3 Unique meaningful GO clusters specific for AD brain.…”
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with typical neuropathological hallmarks, such as neuritic plaques and neurofibrillary tangles, preferentially found at layers III and V. The distribution of both hallmarks provides the basis for the staging of AD, following a hierarchical pattern throughout the cerebral cortex. To unravel the background of this layer-specific vulnerability, we evaluated differential gene expression of supragranular and infragranular layers and subcortical white matter in both healthy controls and AD patients. We identified AD-associated layer-specific differences involving protein-coding and non-coding sequences, most of those present in the subcortical white matter, thus indicating a critical role for long axons and oligodendrocytes in AD pathomechanism. In addition, GO analysis identified networks containing synaptic vesicle transport, vesicle exocytosis and regulation of neurotransmitter levels. Numerous AD-associated layer-specifically expressed genes were previously reported to undergo layer-specific switches in recent hominid brain evolution between layers V and III, i.e., those layers that are most vulnerable to AD pathology. Against the background of our previous finding of accelerated evolution of AD-specific gene expression, here we suggest a critical role in AD pathomechanism for this phylogenetic layer-specific adaptation of gene expression, which is most prominently seen in the white matter compartment.
“…While these underlying mechanisms have been specifically proposed for ARHL, loss of peripheral vestibular input would also be expected to have enormous consequences for cognition given the vast network in the cerebral cortex activated by vestibular stimulation (Lobel et al, 1998;Brandt and Dieterich, 1999;Lopez et al, 2012). Importantly, these underlying mechanisms may interact with one another in complex ways (Johnson et al, 2020), and recent works suggest that distinct mechanisms may be responsible, with different types of dementia associated with different patterns of hearing loss (Jung et al, 2021).…”
Section: Mechanisms Underlying Age-related Neurodegeneration Inform Age-related Pathology In the Cochlea And Vestibular End Organsmentioning
confidence: 99%
“…Like Alzheimer's disease, Parkinson's disease and the related Lewy body disease are also associated with cognitive impairment in middle to late life and both peripheral auditory and vestibular impairment (Hardy et al, 2016;Jafari et al, 2020;Johnson et al, 2020). Multiple studies report increased audiometric hearing thresholds (after adjustment for the effect of ARHL) in patients with Parkinson's disease and reduced otoacoustic emission (OAE) amplitudes (reviewed in Jafari et al, 2020;De Groote et al, 2021).…”
Section: Mechanisms Underlying Age-related Neurodegeneration Inform Age-related Pathology In the Cochlea And Vestibular End Organsmentioning
Both age-related hearing loss (ARHL) and age-related loss in vestibular function (ARVL) are prevalent conditions with deleterious consequences on the health and quality of life. Age-related changes in the inner ear are key contributors to both conditions. The auditory and vestibular systems rely on a shared sensory organ – the inner ear – and, like other sensory organs, the inner ear is susceptible to the effects of aging. Despite involvement of the same sensory structure, ARHL and ARVL are often considered separately. Insight essential for the development of improved diagnostics and treatments for both ARHL and ARVL can be gained by careful examination of their shared and unique pathophysiology in the auditory and vestibular end organs of the inner ear. To this end, this review begins by comparing the prevalence patterns of ARHL and ARVL. Next, the normal and age-related changes in the structure and function of the auditory and vestibular end organs are compared. Then, the contributions of various molecular mechanisms, notably inflammaging, oxidative stress, and genetic factors, are evaluated as possible common culprits that interrelate pathophysiology in the cochlea and vestibular end organs as part of ARHL and ARVL. A careful comparison of these changes reveals that the patterns of pathophysiology show similarities but also differences both between the cochlea and vestibular end organs and among the vestibular end organs. Future progress will depend on the development and application of new research strategies and the integrated investigation of ARHL and ARVL using both clinical and animal models.
“…Therefore, it is mandatory to clarify the mechanisms linking hearing loss to dementia. Several hypotheses have been proposed to explain the relationship between auditory sensory deprivation and cognitive impairment ( Griffiths et al, 2020 ; Johnson et al, 2021 ; Slade et al, 2020 ), but the nature of such association remains controversial.…”
Although association between hearing impairment and dementia has been widely documented by epidemiological studies, the role of auditory sensory deprivation in cognitive decline remains to be fully understood. To address this issue we investigated the impact of hearing loss on the onset and time-course of cognitive decline in an animal model of Alzheimer’s disease (AD), that is the 3×Tg-AD mice and the underlying mechanisms. We found that hearing loss induced by noise exposure in the 3×Tg-AD mice before the phenotype is manifested caused persistent synaptic and morphological alterations in the auditory cortex. This was associated with earlier hippocampal dysfunction, increased tau phosphorylation, neuroinflammation, and redox imbalance, along with anticipated memory deficits compared to the expected time-course of the neurodegenerative phenotype. Our data suggest that a mouse model of AD is more vulnerable to central damage induced by hearing loss and shows reduced ability to counteract noise-induced detrimental effects, which accelerates the neurodegenerative disease onset.
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