Lila walks into her annual physical ready to express her recent hearing issues. She misses out on her kids’ stories during family dinners, her husband often repeats things to her, and she ends the night with the TV at a blaring volume. “Hearing loss is a common problem as adults get older,” explains her doctor. What Lila didn’t know is that people with hearing loss in mid-life are also more likely to develop Alzheimer’s Disease (AD) later in life. Researchers at the Biomedical Research Institute of New Jersey have been exploring this connection, paving the way for an early biomarker to detect AD risk.

The team focused on the auditory brain circuitry that affects learning and memory, which are the first cognitive abilities affected in Alzheimer’s Disease. They used a hearing test called Auditory Brainstem Response, otherwise known as ABR, to act as an Alzheimer’s Disease biomarker. ABR is a non-invasive test commonly used to screen newborns. It emits a clicking sound and measures electrical activity in the auditory nerve. The team used this same test on a preclinical model featuring two groups of rats, AppS and AppH. The AppS group modeled the aggressive Swedish mutation of AD. This mutation involves the amyloid precursor protein (App), which accumulates into plaques to form one of the hallmark pathologies of the disease. In contrast, the AppH group carried a more common, standard genetic mutation.

ABR produces different waves that are often examined in averages. This study took a significantly new approach by analyzing each ABR trial independently. The team applied mathematical models to track changes in timing, amplitude, shape, and frequency. By measuring the variability in ABR signals, they sought to connect hearing loss and AD.

This analysis successfully separated the at-risk rats from the healthy control rats, accurately predicting which populations were at risk of developing Alzheimer’s purely based on the ABR recordings. The clusters varied depending on sex and age, demonstrating that AD risk manifests differently at different stages of life in the brainstem and across sexes. Additionally, young rats in the study underwent auditory learning, and their ABR results were relatively similar to those of the healthy group. This stayed consistent as the rats aged, indicating auditory training could trigger neuroplasticity and work against cognitive decline.

This study focuses on prodromal differences that appear before cognitive decline and memory loss become apparent, opening the door for hearing tests such as ABR to act as an early warning sign for neurodegenerative conditions.