Distinct disease mechanisms may underlie cognitive decline related to hearing loss in different age groups

Abstract

BackgroundHearing loss in older adults is associated with increased dementia risk. Underlying mechanisms that connect hearing loss with dementia remain largely unclear.MethodsWe studied the association of hearing loss and biomarkers for dementia risk in two age groups with normal cognition: 65 participants from the European Medical Information Framework (EMIF)-Alzheimer’s disease (AD) 90+ study (oldest-old; mean age 92.7 years, 56.9% female) and 60 participants from the EMIF-AD PreclinAD study (younger-old; mean age 74.4, 43.3% female). Hearing function was tested by the ‘digits-in-noise test’ and cognition by repeated neuropsychological evaluation. Regressions and generalised estimating equations were used to test the association of hearing function and PET-derived amyloid burden, and linear mixed models were used to test the association of hearing function and cognitive decline. In the oldest-old group, mediation analyses were performed to study whether cognitive decline is mediated through regional brain atrophy.ResultsIn oldest-old individuals, hearing function was not associated with amyloid pathology (p=0.7), whereas in the younger-old individuals hearing loss was associated with higher amyloid burden (p=0.0034). In oldest-old individuals, poorer hearing was associated with a steeper decline in memory, global cognition and language, and in the younger-old with steeper decline in language only. The hippocampus and nucleus accumbens mediated the effects of hearing loss on memory and global cognition in the oldest-old individuals.ConclusionsHearing loss was associated with amyloid binding in younger-old individuals only, and with cognitive decline in both age groups. These results suggest that mechanisms linking hearing loss with risk for dementia depends on age.

Deafness causing neuroplastin missense variants fail to promote plasma membrane Ca2+-ATPase levels and Ca2+ transient regulation in brain neurons

“…The outer hair cells (OHCs) mechanically amplify sound-induced vibrations and the inner hair cells (IHCs) activate the auditory nerve via ribbon synapses on spiral ganglion neurons ( 2 ). Although the primary auditory cortex is the first target for hearing information, other interconnected brain structures, such as hippocampus, are actively engaged in learning and memorizing behaviorally-relevant auditory cues ( 3 , 4 , 5 ).…”