Abstract
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.
Highlights
Recent epidemiological evidence suggests a strong association between hearing loss and cognitive decline (Gallacher et al, 2012; Thomson et al, 2017; Livingston et al, 2020; Loughrey et al, 2018; Liu and Lee, 2019)
The trend of threshold increase was similar across mid- and high frequencies and no significant differences were observed between 3×Tg -A D and WT mice, indicating that both strains show a similar degree of susceptibility to hearing loss induced by noise
Hearing impairment is known as a major clinical risk factor for cognitive decline (Gates and Mills, 2005; Lin et al, 2011; Loughrey et al, 2018; Griffiths et al, 2020; Johnson et al, 2021), with relevant clinical implications for dementia prevention, diagnosis, and treatment (Dawes et al, 2015; Taljaard et al, 2016; Livingston et al, 2020)
Summary
Recent epidemiological evidence suggests a strong association between hearing loss and cognitive decline (Gallacher et al, 2012; Thomson et al, 2017; Livingston et al, 2020; Loughrey et al, 2018; Liu and Lee, 2019). It has been shown that for every 10 dB increase in hearing loss, there is a 20 % increased risk of developing dementia (Lin et al, 2011). Substantiating such correlation would have significant implications for prevention and treatment of dementia. 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
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