Hearing Loss Comorbidities

Alzheimer’s Disease.  Caring for patients with Alzheimer’s Disease (AD) costs $250 billion dollars every year in the United States, and as such any interventions that might slow its onset would have great value to society. Strikingly, untreated hearing loss in middle age is comorbid with AD at older ages.  The reasons why hearing loss might presage AD are not understood.  There are several potential explanations for why these diseases might co-exist in a patient.  First, both diseases may stem from a common neurodegenerative cause.  Second, it may be difficult for people in the early stages of AD to learn to use a hearing aid, and so they forego treatment.  Third, untreated hearing loss may tax working memory and lead to social isolation, hastening AD onset and progression.  Fourth, individuals with hearing loss may perform poorly on oral AD screening procedures, leading to over-diagnosis.  These explanations are not mutually exclusive, and may apply to different populations.  Nonetheless, if treating hearing loss delays the onset or slows the progression of AD, that would be a finding of great value.  However, confirming hearing loss as a potential biomarker for later AD would also be important.

To better understand this question, we have turned to mouse genetic models of AD.  We are examining the effects of noise damage on mice harboring AD genes. We will determine if the presence of such genes sensitize mice to noise damage, which would suggest that AD can drive hearing loss.  We will also determine if hearing loss accelerates the development of AD symptoms.  Lastly, we will examine the effects of CA-ERBB2 induction in the AD mouse, to determine if hearing restoration is possible in the presence of AD-driving proteins.  These experiments are funded by an NIH Administrative Supplement.

Diabetes.  There are reports suggesting a link between uncontrolled diabetes and hearing loss.  Notably, hyperglycemia, the hallmark of uncontrolled diabetes, has been shown to drive down-regulation and inactivation of the transcription factor FOXO3.  We are investigating the expression of FOXO3 in the cochlea in the context of hyperglycemia in the mouse.  We are also investigating the effects of noise exposure on hearing and cochlear anatomy of hyperglycemic mice.  This project is not yet funded.