۱- Introduction

۲- Methods

۳- Results

۴- Discussion

۵- Conclusions

References

Abstract

Although epidemiological studies have identified an association between hearing loss and cognitive impairment, there is a lack of biological evidence detailing the mechanisms underlying this association. The present study investigated the effects of hearing loss on cognitive impairment using an at-risk model. In this animal model, amyloid-β (Aβ) was administered to the brain to such an extent that it did not cause cognitive impairments but made the brain vulnerable to risk factors. This study included four experimental groups based on hearing level and Aβ administration. Behavioral tests were conducted to evaluate cognitive function, and synaptic protein levels were measured in the hippocampus and prefrontal cortex. The group with hearing loss and Aβ administration showed significantly greater deficits on cognitive tests associated with the hippocampus than the other three groups (only Aβ administration, only hearing loss, and without hearing loss or Aβ administration). The hearing loss and Aβ administration group also had significantly lower levels of synaptic proteins in the hippocampus than the other groups. The present results suggest that hearing loss may act as a risk factor for cognitive impairment in Alzheimer’s disease. Additionally, the present findings indicate hearing loss may cause hippocampal synapses to be more vulnerable to Aβ-induced damage.

Introduction

In 2016, approximately 43.8 million people suffered from dementia worldwide. Furthermore, the worldwide death rate associated with dementia was 2.4 million people, which made it the fifth leading cause of death [1]. The leading cause of dementia is Alzheimer’s disease (AD) [2] and, therefore, there is an urgent need for the development of treatments for AD. Although much research has been conducted in this area, the currently available treatments for AD have yet to achieve significant clinical efficacy in that they can partially stabilize the symptoms of this disease but not correct it [3]. It is also important to identify risk factors for AD, as this information will allow us to develop methods preventing AD development or slowing disease progression. Age, family history, and heredity are the most important risk factors of AD [4] and can be used to predict its occurrence. However, these factors cannot be modified and, thus, cannot contribute to the prevention of AD. Recent epidemiological evidence suggests that there is an association between hearing loss and cognitive impairment [5–۸] and other studies have shown that hearing loss may be a potentially modifiable risk factor of AD [9]. Approximately one-third of elderly people 65 years of age and older have hearing loss, which can be ameliorated by hearing aids and cochlear implants. Therefore, if hearing loss is a risk factor of cognitive impairment and its mechanisms can be identified, then the treatment of hearing loss can contribute to the prevention of AD. However, the causal relationship between hearing loss and AD remains controversial. For example, it has been suggested that the association between hearing loss and AD exists due to difficulties in cognitive function tests that patients with hearing loss experience due to poor verbal communication. Furthermore, the biological mechanisms that underlie this association have yet to be elucidated.