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Hearing impairment was linked to neuropathological hallmarks of dementia, an autopsy study suggested.

In older adults who were cognitively normal, impaired hearing was associated with tau neurofibrillary degeneration, reported Willa Brenowitz, PhD, MPH, of the University of California San Francisco (UCSF), and co-authors.

And in people with dementia, hearing loss was tied to microinfarcts but not to tau tangles, the team wrote in .

"This is really important as it's the first study to show a direct link between hearing loss and greater dementia-related neuropathology," said senior author Kristine Yaffe, MD, also of UCSF.

"It suggests these conditions are related, and we need to determine whether hearing loss leads to greater dementia pathology, or vice versa, or both," Yaffe told 番茄社区.

"While we don't exactly know the direction of the association, this study suggests there is a true link between hearing loss and neurodegeneration," added Brenowitz.

"We are particularly curious about the association of hearing loss prior to dementia onset with tau, and whether hearing loss could be used as part of a screening tool to predict dementia in patients or help identify those who should be followed up for cognitive decline," Brenowitz told 番茄社区.

Several pointers show a possible connection between age-related central auditory processing and dementia, Francesco Panza, MD, PhD, of the National Institute of Gastroenterology Saverio de Bellis Research Hospital in Bari, Italy, and co-authors explained in an .

"The most plausible association is based on the dynamic interaction between auditory and cognitive processing," they wrote. "The evidence for a strong link between age-related central auditory processing disorder and cognition has led to the provocative term 'the cognitive ear' that implies other associative cortical areas process hearing functions in addition to the ear and the auditory cortex."

Sensorial impairment from age-related hearing loss may be a proxy for frailty, Panza and colleagues observed.

"Given that hearing and visual loss in older age are frequent conditions included in many models of frailty, the link between age-related hearing loss and cognitive impairment/dementia in later life may derive from sensorial frailty, a particular frailty phenotype," the editorialists wrote. "Increased perceptual demands due to degraded sensory input, considered as a model of sensorial frailty, recruit cognitive resources into auditory processing."

In their study, Brenowitz and colleagues assessed 2,755 autopsied participants age 55 and older from the National Alzheimer's Coordinating Center (NACC) database. Participants had been followed at one of approximately 30 National Institute on Aging-funded Alzheimer's Disease Centers between 2005 and 2018 and had at least one clinical evaluation no more than 2 years before death.

Baseline clinician reports assessed whether a participant had functional hearing, with or without a hearing aid. People with hearing aids who reported no functional impairment were classified as non-hearing impaired.

Neuropathologies included Alzheimer's disease changes measured by of neuritic plaque densities (extracellular deposits of amyloid beta) and for neurofibrillary tangle pathology. The researchers also looked at Lewy body disease, gross infarcts, and microinfarcts.

Nearly a third of participants (32%) had impaired hearing. A total 580 people were cognitively normal at baseline and 2,175 had dementia, ranging from mild to severe.

In cognitively normal participants, impaired hearing was associated with higher Braak stage (RR 1.33 per two-stage increase, 95% CI 1.06- 1.66), but not with other pathologies.

In participants with dementia, impaired hearing was positively associated with microinfarcts (RR 1.18, 95% CI 1.00-1.39) and inversely associated with neuritic plaque density (RR 0.91 per score increase, 95% CI 0.85-0.99). Impaired hearing in dementia participants was not related to Braak stage, neocortical Lewy bodies, or gross infarcts (all P >0.05).

Over about 4 years of follow-up, development of impaired hearing in people with cognitive impairment was associated with neocortical Lewy bodies (RR 1.26, 95% CI 1.02-1.55).

In a secondary analysis, Brenowitz and her team added autopsy results of 704 people with frontotemporal lobar degeneration (FTLD) to the study, including 415 people with FTLD-tau and 247 with non-tauopathy FTLD. Impaired hearing at baseline was about 20% less likely in FTLD-tau, and there was no association between non-tauopathy FTLD and impaired hearing.

"We saw an inverse association with FTLD-tau," the researchers noted. "Future studies evaluating other tauopathies, such as chronic traumatic encephalopathy, aging-related tau astrogliopathy, etc. may be informative."

The study has several limitations, the researchers said. It relied on clinical judgment of hearing impairment, which could encompass both deficits in peripheral or central auditory processing, muddying the interpretation of the findings. In addition, NACC Alzheimer's Disease Center participants differ from a broader population -- they are mostly white older adults with relatively high socioeconomic status and at high risk for clinical Alzheimer's disease.

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