Tim Tai, Senior Photographer

According to the Alzheimer’s Association, over six million Americans suffer from Alzheimer’s disease, a figure projected to more than double by 2050. However, Yale researchers are taking a new approach to Alzheimer’s research that may help detect the disease up to 10 years before symptoms manifest.

Led by Dr. Hong-Bo Zhao, professor of otolaryngologic surgery at the School of Medicine, the research explores the link between hearing loss and developing Alzheimer’s, the progressive brain disease that results in memory loss and cognitive impairment.

According to Zhao, many scientists in the field recognize that hearing loss can preempt cognitive decline. How exactly hearing dysfunction may be linked to Alzheimer’s, though, is still unclear — a topic that Zhao aims to study through a new $2.4 million grant from the National Institute on Aging announced earlier this month. 

“They encouraged us to perform this kind of study because early diagnosis is crucial for the disease,” Zhao said. “Now maybe we can find a way to block such a degenerative process.”

Currently, there is no effective method to treat or prevent Alzheimer’s disease, and existing treatments depend on detecting the disease as early as possible, Zhao said. An early Alzheimer’s diagnosis and corresponding intervention that delays dementia — the progressive decline of cognitive capability — by just one year could decrease the amount of dementia worldwide by 10 percent.

Zhao believes that even before dementia and other Alzheimer’s symptoms arise, changes in the way the brain processes sound might be an early warning sign for Alzheimer’s disease. His new research aims to explore the link between auditory processing and Alzheimer’s, especially since hearing loss commonly occurs 5-10 years before dementia symptoms show up in patients.

“Very few people study the auditory system changes in Alzheimer’s disease,” Zhao told the news. “Our lab is one of the few labs to perform such a study in the United States.”

With the new grant, Zhao’s lab plans to use mouse models in which researchers modify mouse genes to increase the number of times they are expressed. When the mice overexpress these genes, they show dementia symptoms — effectively guaranteeing that the mice will develop Alzheimer’s.

As the mice grow, Zhao’s team plans to perform RNA sequencing tests on the parts of the mice’s brains linked to auditory processing. The sequencing tests measure genetic changes in the brain areas linked to hearing.

If these changes happen in consistent patterns before the mice exhibit dementia symptoms, the gene changes could be an early indicator for Alzheimer’s — a “biomarker,” Zhao said. 

And just as human patients often have hearing loss before developing Alzheimer’s symptoms, Zhao’s team also plans to evaluate the mice’s hearing before they display signs of dementia, measuring changes in the mice’s brain activity in response to external sounds.

“We basically conduct hearing tests. said Dr. Yang Yang, a postdoctoral associate in Zhao’s lab. “And we do testing like the EEG [electroencephologram] … and try to see if there is any difference.”

One of the challenges the researchers face, though, is to distinguish the symptoms of Alzheimer’s from those of natural aging. According to Yang, age-related hearing loss is difficult to distinguish from hearing loss linked to Alzheimer’s, making it difficult to pinpoint a precise relationship between the two conditions.

For the researchers, overcoming that confounding variable was one reason to opt for the mouse model, where young mice can be evaluated for hearing and memory loss before the symptoms of age set in. 

Even in genetically modified mice as young as three months old, Zhao’s team has observed hearing loss. Their onset of Alzheimer’s occurred at nine months, indicating that dementia — not age — was tied to hearing loss.

Identifying Alzheimer’s biomarkers through auditory pathways may pave the way for advancements in early detection and intervention strategies, Zhao explained. Even if doctors can’t cure the disease, creating reliable ways to detect Alzheimer’s earlier — in this case, through changes in the hearing pathway — could help patients better manage their symptoms and slow the progression of dementia. 

For Zhao’s peers, it’s a promising goal.

“Our Department is very excited that his work may offer breakthrough understanding of Alzheimer’s, a devastating disease that definitely involves the auditory system,” Dr. Joseph Santos-Sacchi, a professor of otolaryngologic surgery, cellular and molecular physiology and neuroscience, wrote to the News.

According to the World Health Organization, one in ten people will have disabling hearing loss by 2050.