The neural mechanisms linking hearing impairment and Alzheimer’s disease involve intricate interactions between auditory processing, neural connectivity, and neurodegenerative processes. Understanding these mechanisms is crucial for unraveling the complex relationship between the two conditions.
Auditory Cortex and Alzheimer’s Pathology:
The auditory cortex, responsible for processing auditory information, has demonstrated interconnections with brain regions affected by Alzheimer’s pathology. Research using neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) has revealed alterations in the auditory cortex in individuals with Alzheimer’s disease. This suggests a potential vulnerability of the auditory system to the neurodegenerative processes characteristic of Alzheimer’s.
Hippocampal and Temporal Lobe Connections:
The hippocampus, a critical structure for memory formation, is highly interconnected with the auditory system. Studies have shown that the temporal lobe, housing both the auditory cortex and the hippocampus, is susceptible to Alzheimer’s-related pathology. The breakdown of neural connections within the temporal lobe may contribute to both memory deficits and auditory processing impairments observed in individuals with Alzheimer’s and hearing impairment.
Impact on White Matter Tracts:
The integrity of white matter tracts, responsible for transmitting signals between different brain regions, is essential for effective communication within the neural network. Hearing impairment has been associated with disruptions in white matter integrity. Changes in the myelin sheath and axonal damage in these tracts may compromise the transmission of neural signals, exacerbating the cognitive decline observed in Alzheimer’s disease.
Common Neurotransmitter Systems:
Both hearing function and cognitive processes rely on shared neurotransmitter systems, such as acetylcholine. Alzheimer’s disease is characterized by a decline in acetylcholine levels, contributing to cognitive deficits. The auditory system, particularly in the central auditory pathway, is also modulated by acetylcholine. Disruptions in these shared neurotransmitter systems may contribute to the overlapping cognitive and auditory impairments seen in individuals with both conditions.
Cumulative Cognitive Load:
Hearing impairment places an additional cognitive load on individuals as they expend greater effort to process auditory information. This increased cognitive load has implications for neural resources. In the context of Alzheimer’s disease, where neural resources are already compromised, the cumulative effect of the cognitive load associated with hearing impairment may contribute to accelerated cognitive decline.
Shared Genetic and Environmental Factors:
Genetic and environmental factors contribute to both hearing impairment and Alzheimer’s disease. Genetic predispositions may influence susceptibility to neurodegenerative processes and impact auditory function simultaneously. Environmental factors, such as exposure to noise, may contribute to both conditions. Understanding the shared genetic and environmental influences can provide insights into the common neural mechanisms at play.
Neuroplasticity and Compensation:
The brain’s capacity for neuroplasticity allows it to adapt to challenges. In the context of hearing impairment, the brain may undergo structural and functional changes as a compensatory response to reduced auditory input. However, in the presence of Alzheimer’s pathology, these compensatory mechanisms may be compromised. Investigating the interplay between neuroplasticity, compensation, and neurodegeneration is crucial for understanding the dynamic nature of the link between hearing impairment and Alzheimer’s.
The relationship between hearing impairment and cognitive decline remains a subject of extensive research, with a recent study conducted within the Rancho Bernardo Study of Healthy Aging shedding light on the intricate connections between hearing ability, brain aging, and microstructural changes in key brain regions.
Study Design and Participants:
The study involved 130 participants (mean age 76.4±7.3 years; 65% women) from the Rancho Bernardo Study of Healthy Aging. In 2003–2005, participants underwent a screening audiogram to assess hearing ability, and in 2014–2016, brain magnetic resonance imaging (MRI) was conducted. The study aimed to determine whether hearing impairment was associated with advanced brain aging or alterations in the microstructure of brain regions involved in auditory and cognitive processing.
Methods and Measures:
Hearing ability was quantified using the average pure tone threshold (PTA) at 500, 1000, 2000, and 4000 Hz in the better-hearing ear. To assess brain aging, the researchers utilized brain-predicted age difference (Brain-pad), calculated as the difference between brain-predicted age based on a validated structural imaging biomarker of brain age and chronological age. Additionally, regional diffusion metrics in temporal and frontal cortex regions were obtained from diffusion-weighted MRIs.
Contrary to expectations, the study found no significant association between PTAs and brain-predicted age difference (β= 0.09; 95% CI: –0.084 to 0.243; p = 0.34). However, an intriguing correlation emerged between hearing impairment and alterations in brain microstructure. PTAs were linked to reduced restricted diffusion and increased free water diffusion primarily in right hemisphere temporal and frontal areas (restricted diffusion: βs = –0.21 to –0.30; 95% CIs from –0.48 to –0.02; ps < 0.03; free water: βs = 0.18 to 0.26; 95% CIs 0.01 to 0.438; ps < 0.04).
The study’s findings challenge the conventional belief that hearing impairment is directly associated with advanced brain aging. Instead, it suggests a more nuanced relationship, wherein hearing loss is linked to specific microstructural changes in brain regions crucial for auditory processing and attentional control. The authors propose that the increased risk of dementia associated with hearing impairment might arise, in part, from compensatory brain changes that, paradoxically, reduce resilience. Further research is warranted to unravel the complexity of these relationships and inform potential interventions to mitigate cognitive decline in individuals with hearing loss.
Unraveling the Molecular Mechanisms of COVID-19-Related Audiovestibular Dysfunction
A staudy reported in “Nature – https://www.nature.com/articles/s43856-021-00044-w#Sec27” represents a pivotal contribution to the field, as it is the first to delve into potential molecular mechanisms underlying audiovestibular dysfunction in patients with COVID-19.
The comprehensive exploration includes a detailed analysis of audiovestibular symptoms in ten patients infected with SARS-CoV-2. The temporal correlation between symptom onset and positive COVID-19 testing strongly implicates SARS-CoV-2 as the causative agent of audiovestibular symptoms. Importantly, none of the patients exhibited evidence of middle ear infection, emphasizing the likelihood of direct viral infection or inflammation affecting the inner ear and cochleovestibular nerve.
Clinical Findings and Implications:
The clinical aspect of the study, while impactful, is constrained by its limited sample size and the unknown prevalence of audiovestibular dysfunction in COVID-19 due to the absence of universal testing during the pandemic. The possibility that more severe cases or those resulting in mortality were not documented introduces a potential bias. Additionally, the lack of histopathologic examination of human inner ears from COVID-19 patients underscores the challenges posed by the organ’s small size and complex anatomy.
Innovative Models to Bridge Gaps:
To overcome these limitations, the study pioneers the development of human in vitro 2D and 3D models of SARS-CoV-2 otic infection derived from hiPSCs. This innovative approach enables the exploration of different cellular mechanisms of audiovestibular dysfunction. The observation that hair cells in all human inner ear tissue models appear to be susceptible to infection provides a valuable mechanistic insight. The expression of SARS-CoV-2 entry genes in mouse hair cells further supports the potential vulnerability of cochlear hair cells, extending the relevance to both auditory and vestibular symptoms.
Contrastingly, inconsistent data on the infection of Schwann cells highlight the need for nuanced exploration. Differences between immature Schwann cell precursors (SCPs) and mature cells in human explants suggest the importance of considering cellular maturation stages. The absence of ACE2 expression in mouse cochlear Schwann cells emphasizes the necessity of using human tissue models for infectious disease studies.
Neuronal Infection and Mechanisms:
Notably, the study unveils evidence of neurons being infected by SARS-CoV-2 in one model of inner ear organoids. This observation, while in a less structured area of the organoid, hints at the potential involvement of neurons in audiovestibular symptoms. The proposed mechanisms for these symptoms encompass direct viral infection and damage to hair cells, triggering an innate interferon-mediated response, and potential damage to the stria vascularis affecting potassium homeostasis.
Multiple Routes of Viral Entry:
The discussion elaborates on several potential routes by which SARS-CoV-2 may access the inner ear, including central nervous system entry via the olfactory groove, entry through the endolymphatic sac, hematogenous spread through the stria vascularis, and traversal through the round or oval window membrane. The acknowledgment of the possibility of multiple entry points underscores the complexity of the virus’s interaction with the auditory and vestibular systems.
Pediatric Implications and Future Directions:
The study’s observation of SARS-CoV-2 infection in otic progenitor cells raises concerns about potential implications for the developing fetal inner ear. While pediatric populations have been largely spared of COVID-19 symptoms, the study suggests a need for continued monitoring of hearing in children born during the pandemic.
Potential paths for SARS-CoV-2 entry into the inner ear.
Arrows indicate potential paths via the nose and olfactory foramina (OF) into the central nervous system; via the endolymphatic sac (ES); via labyrinthine artery (LA) to ultimately reach stria vascularis; via round window (RW) and oval window (OW) membranes which the virus could reach through the Eustachian tube (ET) or external auditory canal (EAC), middle ear and mastoid. The diagram within this figure was drawn by Chris Gralapp and is being reproduced with permission.
reference link : https://content.iospress.com/articles/journal-of-alzheimers-disease/jad230767