The Connection Between Hearing Loss and Dementia

By Alycia Gordan

June is Alzheimer's & Brain Awareness Month and Hearing Health Foundation would like to shine light on the effects untreated hearing loss can have on our brains and memory. Hearing loss is often linked with dementia, and research is being conducted to establish the exact link between the two. Evidence suggests that by treating hearing loss, the risk of dementia can be mitigated.

Dementia is a medical term that is used to describe a host of symptoms, characterized by a deterioration in a patient’s cognitive abilities. The degeneration of brain cells causes neurons to stop functioning, leading to a series of dysfunctions.

A person may have dementia if at least two of his mental faculties are affected: the loss of memory and focus; difficulty communicating; short or interrupted attention spans; impaired judgment; or an inability to perform everyday tasks.

Frank Lin, M.D., Ph.D., an associate professor of otolaryngology and epidemiology at Johns Hopkins University, conducted a study in 2011 in which the mental abilities of 639 cognitively stable individuals were supervised regularly for 12 to 18 years. The results indicated that volunteers with normal hearing were much less susceptible to acquiring dementia while those with mild, moderate, and severe hearing loss were two, three, and five times more susceptible to the disorder, respectively.

Another study conducted by Lin in 2013 involved observing the cognitive abilities of 1,984 older adults over six years. The research concluded that older adults with hearing loss tended to experience 30 to 40 percent accelerated cognitive dysfunction and were at a higher risk of developing dementia.

What Is the Cause?

Since the exact link between hearing loss and dementia is still a mystery, there are theories about how the former may aggravate the latter.

One of the theories suggests that if the brain struggles to cope with degraded sounds, its resources are allocated to processing these sounds and this “cognitive load” causes a decrease in overall cognitive functioning. Moreover, hearing loss accelerates atrophy in the cerebrum which is not exclusive to processing sound as it also plays a role in memory. In addition, it is speculated that social isolation that results from hearing loss causes stress and depression and exacerbates cognitive deterioration.

What Is the Solution?

Not many studies have been conducted to check the influence of treating hearing loss for treating dementia. However, the studies that have been conducted so far do provide considerable hope.

One way to improve profound hearing loss is receiving cochlear implants. French researcher Isabelle Mosnier, M.D., of the Assistance Publique-Hôpitaux de Paris, evaluated the effect of cochlear implants on cognitive functioning in 94 elderly people who had profound deafness (in at least one ear).

Mosnier found that hearing rehabilitation improved not only cognitive functioning of the elderly, but their speech perception as well.

The most direct link between auditory impairment and memory loss is the brain. Thus, any stimulus that helps the brain remain alert will keep the person active too. Hence, researchers are considering the use of music therapy to restore cognitive functions in people who suffer from memory loss.           

Concetta Tomaino, a cofounder of the Institute for Music and Neurological Function, found that music stimulates parts of the brain made inactive by dementia. In a pilot study, music therapy sessions were conducted with 45 individuals with chronic dementia and the results showed that neurological and cognitive abilities improved significantly for those in the music group.

This research shows there are techniques that can aid individuals with dementia and hearing loss. If you or a loved one has hearing problems, please see a hearing health professional to get a hearing test in order to potentially prevent future cognitive issues. 

Alycia Gordan writes for Brain Blog.

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Success of Sensory Cell Regeneration Raises Hope for Hearing Restoration

By St. Jude Children's Research Hospital

Jian Zuo, Ph.D., and his colleagues induced supporting cells located in the inner ear of adult
mice to take on the appearance of immature hair cells and to begin producing some of the signature proteins of hair cells.

In an apparent first, St. Jude Children's Research Hospital investigators have used genetic manipulation to regenerate auditory hair cells in adult mice. The research marks a possible advance in treatment of hearing loss in humans. The study appears today in the journal Cell Reports.

Loss of auditory hair cells due to prolonged exposure to loud noise, accidents, illness, aging or medication is a leading cause of hearing loss and long-term disability in adults worldwide. Some childhood cancer survivors are also at risk because of hair cells damage due to certain chemotherapy agents. Treatment has focused on electronic devices like hearing aids or cochlear implants because once lost, human auditory hair cells do not grow back.

"In this study, we looked to Mother Nature for answers and we were rewarded," said corresponding author Jian Zuo, Ph.D., a member of the St. Jude Department of Developmental Neurobiology. "Unlike in humans, auditory hair cells do regenerate in fish and chicken. The process involves down-regulating expression of the protein p27 and up-regulating the expression of the protein Atoh1. So we tried the same approach in specially bred mice."

By manipulating the same genes, Zuo and his colleagues induced supporting cells located in the inner ear of adult mice to take on the appearance of immature hair cells and to begin producing some of the signature proteins of hair cells.

The scientists also identified a genetic pathway for hair cell regeneration and detailed how proteins in that pathway cooperate to foster the process. The pathway includes the proteins GATA3 and POU4F3 along with p27 and ATOH1. In fact, investigators found that POU4F3 alone was sufficient to regenerate hair cells, but that more hair cells were regenerated when both ATOH1 and POU4F3 were involved.

"Work in other organs has shown that reprogramming cells is rarely accomplished by manipulating a single factor," Zuo said. "This study suggests that supporting cells in the cochlea are no exception and may benefit from therapies that target the proteins identified in this study."

The findings have implications for a phase 1 clinical trial now underway that uses gene therapy to restart expression of ATOH1 to regenerate hair cells for treatment of hearing loss.

ATOH1 is a transcription factor necessary for hair cell development. In humans and other mammals, the gene is switched off when the process is complete. In humans, ATOH1 production ceases before birth.

"This study suggests that targeting p27, GATA3 and POU4F3 may enhance the outcome of gene therapy and other approaches that aim to restart ATOH1 expression," Zuo said.

The research also revealed a novel role for p27. The protein is best known as serving as a check on cell proliferation. However, in this study p27 suppressed GATA3 production. Since GATA3 and ATOH1 work together to increase expression of POU4F3, reducing GATA3 levels also reduced expression of POU4F3. When the p27 gene was deleted in mice, GATA3 levels increased along with expression of POU4F3. Hair cell regeneration increased as well.

"Work continues to identify the other factors, including small molecules, necessary to not only promote the maturation and survival of the newly generated hair cells, but also increase their number," Zuo said.

Bradley J. Walters, Ph.D. was a 2012 Hearing Health Foundation Emerging Research Grants recipient. This article was repurpsed with permission. 

A Balancing Act Before the Onset of Hearing

By Sonja J. Pyott, Ph.D.

Our ability to hear relies on the proper connections between the sensory hair cells in the inner ear and the brain. Activity of the sensory hair cells (red) and these connections ( green) before hearing begins is essential for the proper development of hearing. The research conducted by Sonja J. Pyott, Ph.D., and colleagues investigated the mechanisms that regulate this activity.

The development of the auditory system begins in the womb and culminates in a newborn’s ability to hear upon entering the world. While the age at which hearing begins varies across mammals, the sensory structures of the inner ears are active before the onset of hearing. This activity instructs the maturation of the neural connections between the inner ear and brain, an essential component of the proper development of hearing. However, we still know very little about the mechanisms regulating the activity of these sensory structures and their neural connections, specifically during the critical period just before the onset of hearing.

In our paper, “mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochlea,” soon to be published in an upcoming issue of The Journal of Physiology, we investigate the role of glutamate, a neurotransmitter, in regulating activity of the sensory structures and their connections in the inner ear before the start of hearing.

Neurotransmitters assist in the communication between neurons and are typically classified as either excitatory or inhibitory based on their action. Excitatory action results in stimulation; inhibitory action assists in the calming of the brain. Our research found that although glutamate typically excites activity, it also elicits inhibitory activity. This dual role for glutamate occurs because it activates two distinct classes of glutamate receptors: ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs).

Importantly, this dual activation balances excitatory and inhibitory activity of the sensory structures, a balance of which is likely important in the final refinement of the neural connections between the inner ear and brain prior to the onset of hearing.

As part of future research, we will further investigate the role of mGluRs, one the distinct classes of glutamate receptors, in the development of hearing. We will also investigate if mGluRs balance excitatory and inhibitory activity in the adult inner ear, similar to its role prior to the onset of hearing. Insights into these mechanisms may identify new ways to modulate activity and prevent congenital or acquired hearing loss.

Study coauthor Sonja J. Pyott, Ph.D., was a 2007 and 2008 Hearing Health Foundation Emerging Research Grants recipient.

We need your help supporting innovative hearing and balance science through our Emerging Research Grants program. Please make a contribution today.

Cortical Alpha Oscillations Predict Speech Intelligibility

By Andrew Dimitrijevic, Ph.D.

Hearing Health Foundation Emerging Research Grants recipient Andrew Dimitrijevic, Ph.D., and colleagues recently published “Cortical Alpha Oscillations Predict Speech Intelligibility” in the journal Frontiers in Human Neuroscience.

The scientists measured brain activity that originates from the cortex, known as alpha rhythms. Previous research has linked these rhythms to sensory processes involving working memory and attention, two crucial tasks for listening to speech in noise. However, no previous research has studied alpha rhythms directly during a clinical speech in noise perception task. The purpose of this study was to measure alpha rhythms during attentive listening in a commonly used speech-in-noise task, known as digits-in-nose (DiN), to better understand the neural processes associated with speech hearing in noise.

Fourteen typical-hearing young adult subjects performed the DiN test while wearing electrode caps to measure alpha rhythms. All subjects completed the task in active and passive listening conditions. The active condition mimicked attentive listening and asked the subject to repeat the digits heard in varying levels of background noise. In the passive condition, the subjects were instructed to ignore the digits and watch a movie of their choice, with captions and no audio.

Two key findings emerged from this study in regards to the influence of attention, individual variability, and predictability of correct recall.

First, the authors concluded that the active condition produced alpha rhythms, while passive listening yielded no such activity. Selective auditory attention can therefore be indexed through this measurement. This result also illustrates that these alpha rhythms arise from neural processes associated with selective attention, rather than from the physical characteristics of sound. To the authors’ knowledge, these differences between passive and active conditions have not previously been reported.

Secondly, all participants showed similar brain activation that predicted when one was going to make a mistake on the DiN task. Specifically, a greater magnitude in one particular aspect of alpha rhythms was found to correlate with comprehension; a larger magnitude on correct trials was observed relative to incorrect trials. This finding was consistent throughout the study and has great potential for clinical use.

Dimitrijevic and his colleagues’ novel findings propel the field’s understanding of the neural activity related to speech-in-noise tasks. It informs the assessment of clinical populations with speech in noise deficits, such as those with auditory neuropathy spectrum disorder or central auditory processing disorder (CAPD).

Future research will attempt to use this alpha rhythms paradigm in typically developing children and those with CAPD. Ultimately, the scientists hope to develop a clinical tool to better assess listening in a more real-world situation, such as in the presence of background noise, to augment traditional audiological testing.

Andrew Dimitrijevic, Ph.D., is a 2015 Emerging Research Grantee and General Grand Chapter Royal Arch Masons International award recipient. Hearing Health Foundation would like to thank the Royal Arch Masons for their generous contributions to Emerging Research Grants scientists working in the area of central auditory processing disorders (CAPD). We appreciate their ongoing commitment to funding CAPD research.

We need your help supporting innovative hearing and balance science. Please make a contribution today.

John Brigande provides commentary: Hearing in the mouse of Usher

Oregon Health & Science University

The March issue of Nature Biotechnology brings together a set of articles that provide an overview of promising RNA-based therapies and the challenges of clinical validation and commercialization. In his News and Views essay, “Hearing in the mouse of Usher,” John V. Brigande, Ph.D., provides commentary on two studies in the issue that report important progress in research on gene therapy for the inner ear.

One in eight people in the United States aged 12 years or older has hearing loss in both ears. That figure suggests that, if you don’t have hearing loss, you likely know someone who does. Worldwide, hearing loss profoundly interferes with life tasks like learning and interpersonal communication for an estimated 32 million children and 328 million adults worldwide. Inherited genetic mutations cause about 50 percent of these cases.

The challenge in developing gene therapy for the inner ear isn’t a lack of known genes associated with hearing loss, but a lack of vectors to deliver DNA into cells. Brigande, associate professor of otolaryngology and cell, developmental, and cancer biology at the OHSU School of Medicine, provides perspective on companion studies that demonstrate adeno-associated viral vectors as a potent gene transfer agent for cochlear cell targets.

The first study demonstrates safe and efficient gene transfer to hair cells of the mouse inner ear using a synthetic adeno-associated viral vector that promises to be a powerful starting point for developing appropriate vectors for use in the human inner ear. The second study demonstrates that a single neonatal treatment with this viral vector successfully delivers a healthy gene to the inner ear to achieve unprecedented recovery of hearing and balance in a mouse model of a disease called Usher syndrome. Individuals with Usher syndrome type 1c are born deaf and with profound balance issues and experience vision loss by early adolescence. The research teams were led by scientists from the Harvard School of Medicine.

Brigande sees these new studies as potentially spurring investment and kickstarting the development of new approaches to correct a diverse set of deafness genes. 

Hearing Restoration Project consortium member John V. Brigande, Ph.D., is a developmental neurobiologist at the Oregon Hearing Research Center. He also teaches in the Neuroscience Graduate Program and in the Program in Molecular and Cellular Biology at the Oregon Health & Science University. This blog was reposted with the permission of Oregon Health & Science University.

Second Cause of Hidden Hearing Loss Identified

By Michigan Medicine - University of Michigan

Some people can pass a hearing test but have trouble understanding speech in a noisy environment. New research identifies a new mechanism for this condition just years after its discovery. Credit: Michigan Medicine

Patients who complain they can't hear their friends at a noisy restaurant, but pass a hearing test in their doctor's office, may be describing hidden hearing loss.

Now, less than six years since its initial description, scientists have made great strides in understanding what hidden hearing loss is and what causes it. In research published in Nature Communications, University of Michigan researchers report a new unexpected cause for this auditory neuropathy, a step toward the eventual work to identify treatments.

"If people can have hidden hearing loss for different reasons, having the ability to make the right diagnosis of the pathogenesis will be critical," says author Gabriel Corfas, Ph.D., director of the Kresge Hearing Research Institute at Michigan Medicine's Department of Otolaryngology -- Head and Neck Surgery.

Corfas published the research with co-author Guoqiang Wan, now with Nanjing University in China. They discovered using mice that disruption in the Schwann cells that make myelin, which insulates the neuronal axons in the ear, leads to hidden hearing loss. This means hidden hearing loss could be behind auditory deficits seen in acute demyelinating disorders such as Guillain-Barré syndrome, which can be caused by Zika virus.

Corfas and Wan used genetic tools to induce loss of myelin in the auditory nerve of mice, modeling Guillain-Barré. Although the myelin regenerated in a few weeks, the mice developed a permanent hidden hearing loss. Even after the myelin regenerated, damage to a nerve structure called the heminode remained.

Synapse loss versus myelin disruption

When the ear is exposed to loud noises over time, synapses connecting hair cells with the neurons in the inner ear are lost. This loss of synapses has previously been shown as a mechanism leading to hidden hearing loss.

In an audiologist's quiet testing room, only a few synapses are needed to pick up sounds. But in a noisy environment, the ear must activate specific synapses. If they aren't all there, it's difficult for people to make sense of the noise or words around them. That is hidden hearing loss, Corfas says.

"Exposure to noise is increasing in our society, and children are exposing themselves to high levels of noise very early in life," Corfas says. "It's clear that being exposed to high levels of sound might contribute to increases in hidden hearing loss."

The newly identified cause -- deficiency in Schwann cells -- could occur in individuals who have already had noise exposure-driven hidden hearing loss as well. "Both forms of hidden hearing loss, noise exposure and loss of myelin, can occur in the same individual for an additive effect," Corfas says.

Previously, Corfas' group succeeded in regenerating synapses in mice with hidden hearing loss, providing a path to explore for potential treatment.

While continuing this work, Corfas started to investigate other cells in the ear, which led to uncovering the new mechanism.

There are no current treatments for hidden hearing loss. But as understanding of the condition improves, the goal is for the research to lead to the development of drugs to treat it.

"Our findings should influence the way hidden hearing loss is diagnosed and drive the future of clinical trials searching for a treatment," Corfas says. "The first step is to know whether a person's hidden hearing loss is due to synapse loss or myelin/heminode damage."

Materials provided by Michigan Medicine - University of Michigan. Co-author Guoqiang Wan, Ph.D., was a 2014 Emerging Research Grants recipient funded by the Wes Bradley, M.D. Memorial Grant.

We need your help in funding the exciting work of hearing and balance scientists.

To donate today to support HHF's groundbreaking research, please visit hhf.org/donate.

Celebrating Hearing Innovations

By Frankie Huang

On Feb. 25, Hearing Health Foundation is celebrating International Cochlear Implant Day to raise awareness of this life-changing technology. Cochlear implants greatly enhance the lives of individuals with severe to profound hearing loss and individuals who don’t benefit from the use of hearing aids. Did you know that as of November 2012, there are 324,000 cochlear implants in use worldwide, and that number is growing daily!

Cochlear implants (CI) are electronic medical devices that are implanted via a surgical procedure. Although implants replace the function of the damaged inner ear, it is important to remember that CIs do not restore normal hearing but work by bypassing damaged structures in the inner ear and stimulating the auditory nerve. This sends signals to the brain, allowing the user to perceive sounds.

Researchers found that children 5 years or older with bilateral severe or profound hearing loss who are implanted with CIs have better speech perception and development over time than children treated with hearing aids. In addition, children with profound hearing loss who used CIs showed greater development of preverbal behavior than those using hearing aids.

Other researchers found that children receiving CIs before 24 months of age greatly benefit in terms of their overall language development. Levels of spoken language in children implanted before age 24 months were on par with their typical hearing peers by age 4.5, but those implanted after age 24 months did not “catch up” with hearing peers by age 4.5. It’s important to note the study didn’t evaluate language development or ongoing delays after age 4.5.

HHF is proud to have supported research in the 1970s that led to the development of cochlear implants. Since then the technology has continued to evolve and improve in order to increase the benefits yielded from having a cochlear implant and to reduce risks associated with an invasive surgical procedure. By further improving the design and the function of CIs, researchers may find a way to maximize all the possible benefits for the patient, to preserve residual hearing, and to improve the health of the inner ear.

If you’re interested in funding research related to hearing loss technology,
please consider donating today at hhf.org/donate or contact us at development@hhf.org.

When It's Not Just Hearing Loss

By Morgan Leppla & Laura Friedman

This year Autism Sunday, an international day to raise awareness of autism spectrum disorder (ASD), is on Feb. 12.

Did you know that one third or more of pediatric hearing loss cases overlap with another condition? This may sometimes be ASD, making treatment and management of co-occurring conditions a challenge.

In a 2007 report in the Journal of Deaf Studies and Deaf Education, British researcher Lindsay Edwards, Ph.D., cites an estimate that 30 to 40 percent of children with hearing loss have co-occurring conditions that could prohibit them from forming language, speech, and sociocognitive skills. But despite this large percentage, there is little research on hearing loss that occurs with other disorders. What research there is has shown the benefit of cochlear implantation for children with additional needs (such as physical or learning disabilities), and the difficulties of language acquisition and development for 3-year-olds with developmentally related conditions such as ASD, cerebral palsy, or Down syndrome.

One silver lining is that the fact that 30 to 40 percent of pediatric hearing loss may occur with other conditions may prove helpful in predicting future disorders. A July 2016 Autism Research paper suggests that a noninvasive measure of otoacoustic emissions in the inner ear—a common hearing test for infants, who are preverbal—may help identify the risk of ASD at an early age, accelerating treatment. Study author Anne Luebke, Ph.D., of University of Rochester Medical School, found that children with ASD often have trouble hearing a frequency range (1–2 kHz) that is important for understanding speech. The range includes sounds for the meaning-conveying consonants S-, H-, and F-.

Scientific conclusions can help shape future research, but cannot illustrate daily life for families with children with co-occurring conditions. Dual diagnoses make unlocking any child’s learning style challenging, but reviving research and upgrading professional training are essential tools in order to advocate for and successfully educate children with co-occurring conditions.

If you’re interested in funding research related to diagnosing and treating co-occuring disorders, such as hearing loss and autism, please consider donating today: hhf.org/donate or contact us at development@hhf.org.

This blog was adapted from an article original appearing in Hearing Health magazine’s Fall 2016 issue. For references in this story, see hhf.org/fall2016_references.

A Fight Against Cancer Is a Fight Against Hearing Loss

By Frankie Huang

In honor of World Cancer Day on February 4, Hearing Health Foundation (HHF) wants to raise awareness of the connection between cancer and hearing loss. Every year, 8.2 million people worldwide die from cancer, a disease that is responsible for 13% of all deaths globally.

Depending on the type of cancer, patients that undergo chemotherapy are sometimes required to take certain drugs that could cause many side effects, including hearing loss. Cisplatin is a chemotherapy drug that is often used to treat testicular, bladder, ovarian and lung cancers. However, an excessive dose of cisplatin can be ototoxic (toxic to the ear), which could lead to temporary or permanent hearing loss.

One study suggested that cisplatin-induced hearing loss is generally bilateral (both ears) and irreversible. The study also found that cisplatin accumulates in cochlear tissue, preventing the cochlea from flushing out toxins. The same researchers found that patients receiving doses of cisplatin between 150-225 mg/m2 showed some degree of hearing loss. For testicular cancer patients, more than 50% of the patients that took cisplatin in doses greater than 400 mg/m2 had permanent hearing loss. Hearing loss may occur within hours or days after the treatment, or hearing may gradually decline after completion of therapy. After following up more than two years later, the study authors found that 44% of patients who took cisplatin had significant hearing loss.

In another recent study, researchers found that the WFS1 gene is associated with cisplatin-related ototoxicity; the heavier the dose, the more severe the hearing loss. Also, a mutation of the WFS1 gene results in Wolfram syndrome, a disorder with deafness as a major symptom.

As of now, there are no safe and protective agents against cisplatin, but scientists are hard at work to find a protective agent that would eliminate the negative side effects of cisplatin. Currently there’s a solution for children that are receiving cisplatin-based chemotherapy: The use of sodium thiosulfate may minimize or protect children and adolescents against cisplatin-induced hearing loss. HHF hopes more preventative therapies and cures for hearing loss can be discovered for all cisplatin-treated patients.

Interested in funding research in this area? Email us at development@hhf.org.