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Researchers Find New Possible Link Between Alzheimer’s Disease and Hearing Loss

Using mouse models, researchers at the University of Rochester Medical Center found that the location of amyloid plaques in the brains of Alzheimer's patients could be important in hearing decline and that auditory brainstem responses (ABR) might help with diagnosis.

Alzheimers Nerve Cells Plaques

Amyloid plaques are aggregates of abnormal proteins that form in the spaces between nerve cells and are thought to play a key role in Alzheimer's disease (AD). The amyloid plaques first develop in the areas of the brain concerned with memory and other cognitive functions, but new research shows how they may also negatively affect hearing.

The link between hearing loss and Alzheimer’s disease (AD)—as well as other forms of dementia and cognitive dysfunction—has been known for at least two decades. Notably, in 2011, Johns Hopkins researcher Frank Lin, MD, PhD, reported that mild hearing loss doubled dementia risk, moderate loss tripled risk, and people with hearing loss were five times more likely to develop dementia.

But what might be the reasons for this? Various theories include a “common cause hypothesis” where a physical problem like blood flow or cardiovascular disease might spur on both hearing loss and cognitive decline; social disengagement due to hearing loss might lead to loneliness, depression, and accelerated brain atrophy; or increased “cognitive load” where the brain must work harder in order to perceive speech resulting in the reallocation of mental resources.

New research from the University of Rochester Medical Center may shed some light on at least one more possible factor. Neuroscience graduate student Daxiang Na and his colleagues were investigating the central auditory activity in two mouse models of AD (5xFAD and APP/PS1). The study aimed to understand the relationship between AD pathology and central auditory processing disorder (CAPD) which is associated with “hidden hearing loss” (a condition where people can struggle with speech understanding even though their standard hearing test results are "normal").

While looking at the data, Na uncovered something unexpected when inspecting the amyloid plaques that may play a key role in AD: in older mice, the plaques were more frequently located in the auditory processing regions and therefore could contribute to hearing loss. While analyzing the two different mouse strains/models with the disease, he found that the older 5xFAD mice had hearing changes like those in people with AD. The other APP/PS1 model did not demonstrate these hearing changes, nor did younger mice in the 5xFAD group.

“It was a chance observation,” said Na, who is the lead author of the study published in the May 26 online edition of Frontiers in Neuroscience.  “Both mouse models had amyloid beta protein, but where we found the plaque varied, and that may be why hearing loss varied across the groups.”

Researchers found that the brains of older mice from both models had plaques in the hippocampus and auditory cortex. But the brains of mice with hearing changes also had a small amount of plaque on the auditory brainstem, suggesting this area may be sensitive to disruption from plaque found in Alzheimer’s. They also discovered that the plaque reduced the brainstem’s ability to coordinate responses to sound.

“This may explain why Alzheimer’s patients have auditory symptoms,” said Patricia White, PhD, professor of Neuroscience and senior author of the study in a press statement. “We think the location of plaques may be more important to hearing decline. It could be a potential biomarker to track disease progression because it could be assessed with amyloid PET imaging. Our data also suggest that regular Auditory Brainstem Response [ABR] assessments could help with diagnosis.”

Daxiang Na Patricia White Univ Rochester

Daxiang Na and Patricia White, PhD, of the White Lab at the University of Rochester.

Diving deeper into auditory dysfunction and AD

The researchers used auditory brainstem response (ABR) waveforms to observe distinct patterns in the two mouse models. The 5xFAD mice showed increased central gain, indicating central hyperactivity, but the APP/PS1 mice exhibited reduced central gain. Furthermore, the 5xFAD mice experienced a more significant hearing loss than the APP/PS1 mice. Interestingly, the central gain increase in the 5xFAD mice occurred before other hearing-related changes, suggesting this might be an early indicator of auditory dysfunction in AD.

Regarding the specific brain regions affected, the researchers found that plaque deposition in 5xFAD mice significantly increased in auditory cortical regions, the auditory thalamus (MGB), and superior regions of the auditory brainstem prior to the central gain increase. However, these increases were not observed in the APP/PS1 mice, where central gain changes were absent.

Additionally, the authors say this was also the first time a deficit for hearing in noise—one of the core symptoms of CAPD—was observed in 5xFAD mice. They note the “experiments add to the growing body of literature consistent with the interpretation that plaque deposition in mouse models of amyloidosis correlate with central auditory processing disorder.”

Toward better explanations for AD patients with hearing loss

Hearing loss in AD remains something of a mystery. The present study revealed that the severity of hearing loss varied between the 5xFAD and APP/PS1 mice, possibly meaning that different plaque accumulation rates influence hearing loss progression. The pattern of hearing loss in the 5xFAD mice—characterized by a significant increase in ABR thresholds at lower frequencies—differed from typical presbycusis.

The researchers note that more longitudinal studies are needed to validate these findings and explore clinical applications. Monitoring ABRs over time might assist in identifying different patient populations and guiding future treatment. Ultimately, a deeper understanding of the link between auditory dysfunction and AD pathology should improve patient care and enhance the quality of life for individuals affected by AD.

Of course, as noted previously, there are several other possible factors linking hearing loss to cognitive decline. The present findings only add to this list of possibilities.

The research was conducted in the White Lab at the Del Monte Institute for Neuroscience at the University of Rochester. Additional authors in the study included Jingyuan Zhang, PhD, Holly Beaulac, PhD, Dorota Piekna-Przybylska, PhD, Paige Nicklas, and Amy Kiernan, PhD, of the University of Rochester Medical Center. Support for the research came from the National Institute of Health, National Institute on Aging.

Original study citation: Na D, Zhang J, Beaulac HJ, Pikna-Przybylska D, Nicklas PR, Kiernan AE, White PM. Increased central auditory gain in 5xFAD Alzheimer’s disease mice as an early biomarker candidate for Alzheimer’s disease diagnosis. Front Neurosci. 2023;17. Published online May 26, 2023. doi.org/10.3389/fnins.2023.1106570

Source: University of Rochester Medical Center and HearingTracker