Do auditory tests predict future alzheimer's disease pathophysiology - hearing loss has been considered a risk factor for alzheimer's disease (ad), but the underlying mechanism remains elusive

A "bottom-up" hypothesis has been suggested, where peripheral or cochlear damage at the "bottom" of the auditory pathway accelerates ad pathophysiology by sensory deprivation. This hypothesis is attractive because IT suggests interventions to improve hearing might slow or prevent progression towards dementia. Alternatively, a "top-down" relationship may exist where protein deposition within the brain at the "top" of the central auditory processing pathway impairs the brain's ability to process sound. Our group studies how conditions that produce diffuse brain damage, such as HIV infection, affect the brain's ability to process complex sounds (central auditory processing). The results show a relationship between performance on central auditory processing tests and cognitive function in individuals living with HIV. This finding led to a NIH-funded supplement to our HIV work to examine these associations in ad. Ad is the leading cause of dementia and is defined by the presence of cerebral amyloid-Β plaques and TAU neurofibrillary tangles. Our results from the supplement show that amyloid-Β plaques and TAU tangles detected by pet correlate better with central, rather than peripheral, auditory test results in a sample containing both mild cognitive impaired due to ad and cognitively unimpaired individuals. The present project will expand this work and assess the relationship of both peripheral and central auditory test performance to longitudinal amyloid-Β and TAU tangle deposition in the brain. The relationship to cognitive performance will also be examined. If the "bottom-up" hypothesis is correct, individuals with poor peripheral hearing at baseline, but age and hearing level appropriate central auditory test results, should show a faster rate of protein accumulation over time compared to those who do not. If the "top-down" hypothesis is correct, poor baseline central auditory test performance, relative to age and peripheral hearing function, should show a strong relationship to the rate of brain protein deposition. These findings could provide a mechanistic understanding of the relationship of performance on auditory tests to ad pathophysiology. Also, auditory tests are objective, straightforward, and relatively insensitive to educational and socioeconomic status. If they predict, or correspond with, anatomic disruption in ad, they may be useful for assessing disease progression or the response to treatment over time. The proposal will leverage, and enroll participants into, the triad cohort, a longitudinal biomarkers-based cohort at the mcgill university research center for studies in aging. Participants in this cohort, have pet imaging to detect amyloid-Β and TAU protein aggregation. In addition to imaging, neurocognitive testing is performed and biosamples (including cerebrospinal fluid) are collected. These data, combined with the auditory tests, will provide the unique ability to determine the relationship between auditory function and multiple biomarkers associated with ad.