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Physiological, Histological, and Cognitive Characterization of a Macaque Model of Presbycusis

Swarat S. KulkarniiD, Amy N. ConneriD, Oscar RausisiD, D. PitchfordiD, Zhengyang WangiD, Aneesh BatchuiD, Leslie W. LibermaniD, M. Charles LibermaniD, Christos ConstantinidisiD, Troy A. HackettiD, Ramnarayan RamachandraniD

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Abstract

Age-related hearing loss (ARHL), or presbycusis, is one of the most prevalent sensory deficits in older adults and has been increasingly implicated in cognitive decline and dementia. This study characterizes ARHL in a rhesus macaque model by combining histological, physiological, and cognitive assessments. Aged macaques exhibited progressive cochlear degeneration, with marked outer hair cell loss at mid-to-high frequencies, elevated auditory thresholds, reduced distortion product otoacoustic emissions, and impaired auditory brainstem responses including amplitude reduction, latency prolongation, and diminished temporal precision. Despite modest reductions in inner hair cell ribbon synapse counts, hypertrophic changes were observed. These auditory deficits correlated with subtle impairments in visual working memory, as measured by a delayed match-to-sample task, underscoring a potential sensory-cognitive link. By capturing cross-domain aging markers in a translationally relevant primate model, this work lays a foundation for mechanistic studies and therapeutic interventions targeting both hearing and cognition in aging populations.

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