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September 22, 2020; 95 (12) Article

Clinician-judged hearing impairment and associations with neuropathologic burden

Willa D. Brenowitz, Lilah M. Besser, Walter A. Kukull, C. Dirk Keene, M. Maria Glymour, Kristine Yaffe
First published August 5, 2020, DOI: https://doi.org/10.1212/WNL.0000000000010575
Willa D. Brenowitz
From the Departments of Psychiatry and Behavioral Sciences (W.D.B., K.Y.) and Neurology (K.Y.), Weill Institute for Neurosciences, and Department of Epidemiology & Biostatistics (M.M.G., K.Y.), University of California, San Francisco; Florida Atlantic University (L.M.B.), Institute for Human Health and Disease Intervention, School of Urban and Regional Planning, Boca Raton; National Alzheimer's Coordinating Center (W.A.K.), Department of Epidemiology, and Department of Pathology (C.D.K.), University of Washington, Seattle; and San Francisco VA Health Care System (K.Y.), CA.
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Lilah M. Besser
From the Departments of Psychiatry and Behavioral Sciences (W.D.B., K.Y.) and Neurology (K.Y.), Weill Institute for Neurosciences, and Department of Epidemiology & Biostatistics (M.M.G., K.Y.), University of California, San Francisco; Florida Atlantic University (L.M.B.), Institute for Human Health and Disease Intervention, School of Urban and Regional Planning, Boca Raton; National Alzheimer's Coordinating Center (W.A.K.), Department of Epidemiology, and Department of Pathology (C.D.K.), University of Washington, Seattle; and San Francisco VA Health Care System (K.Y.), CA.
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Walter A. Kukull
From the Departments of Psychiatry and Behavioral Sciences (W.D.B., K.Y.) and Neurology (K.Y.), Weill Institute for Neurosciences, and Department of Epidemiology & Biostatistics (M.M.G., K.Y.), University of California, San Francisco; Florida Atlantic University (L.M.B.), Institute for Human Health and Disease Intervention, School of Urban and Regional Planning, Boca Raton; National Alzheimer's Coordinating Center (W.A.K.), Department of Epidemiology, and Department of Pathology (C.D.K.), University of Washington, Seattle; and San Francisco VA Health Care System (K.Y.), CA.
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C. Dirk Keene
From the Departments of Psychiatry and Behavioral Sciences (W.D.B., K.Y.) and Neurology (K.Y.), Weill Institute for Neurosciences, and Department of Epidemiology & Biostatistics (M.M.G., K.Y.), University of California, San Francisco; Florida Atlantic University (L.M.B.), Institute for Human Health and Disease Intervention, School of Urban and Regional Planning, Boca Raton; National Alzheimer's Coordinating Center (W.A.K.), Department of Epidemiology, and Department of Pathology (C.D.K.), University of Washington, Seattle; and San Francisco VA Health Care System (K.Y.), CA.
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M. Maria Glymour
From the Departments of Psychiatry and Behavioral Sciences (W.D.B., K.Y.) and Neurology (K.Y.), Weill Institute for Neurosciences, and Department of Epidemiology & Biostatistics (M.M.G., K.Y.), University of California, San Francisco; Florida Atlantic University (L.M.B.), Institute for Human Health and Disease Intervention, School of Urban and Regional Planning, Boca Raton; National Alzheimer's Coordinating Center (W.A.K.), Department of Epidemiology, and Department of Pathology (C.D.K.), University of Washington, Seattle; and San Francisco VA Health Care System (K.Y.), CA.
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Kristine Yaffe
From the Departments of Psychiatry and Behavioral Sciences (W.D.B., K.Y.) and Neurology (K.Y.), Weill Institute for Neurosciences, and Department of Epidemiology & Biostatistics (M.M.G., K.Y.), University of California, San Francisco; Florida Atlantic University (L.M.B.), Institute for Human Health and Disease Intervention, School of Urban and Regional Planning, Boca Raton; National Alzheimer's Coordinating Center (W.A.K.), Department of Epidemiology, and Department of Pathology (C.D.K.), University of Washington, Seattle; and San Francisco VA Health Care System (K.Y.), CA.
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Clinician-judged hearing impairment and associations with neuropathologic burden
Willa D. Brenowitz, Lilah M. Besser, Walter A. Kukull, C. Dirk Keene, M. Maria Glymour, Kristine Yaffe
Neurology Sep 2020, 95 (12) e1640-e1649; DOI: 10.1212/WNL.0000000000010575

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Abstract

Objective To examine whether neuropathologic burden is associated with hearing impairment.

Methods We studied 2,755 autopsied participants ≥55 years of age from the National Alzheimer's Coordinating Center database. Participants had at least 1 clinical evaluation at US National Institute on Aging–funded Alzheimer's Disease Center no more than 2 years before death. Patients were classified as hearing impaired by clinician report at baseline. Common dementia neuropathologies included Alzheimer disease pathologic change (Consortium to Establish a Registry for Alzheimer's Disease neuritic plaque density, neurofibrillary degeneration Braak stage), Lewy body disease, gross infarcts, and microinfarcts. Logistic regression models predicted impaired hearing with adjustment for age at death, sex, race, education, center, and follow-up time. Relative risks were calculated with the use of marginal standardization.

Results Impaired hearing was common (32%). In participants who were cognitively normal at baseline (n = 580), impaired hearing was associated with higher Braak stage (relative risk [RR] 1.33 per 2-stage increase, 95% confidence interval [CI] 1.06–1.66) but not other pathologies. In participants with dementia (n = 2,175), 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). Development of impaired hearing in those with cognitive impairment was associated with neocortical Lewy bodies (1.26, 95% CI 1.02–1.55).

Conclusions Impaired hearing, reported before the onset of cognitive impairment, was associated with increased neurofibrillary tangle burden. Impaired hearing in those with cognitive impairment was associated with microinfarcts and neocortical Lewy bodies but not typical Alzheimer disease pathologic change. Functional hearing problems may be a preclinical marker of neurofibrillary neurodegeneration, although replication is needed.

Glossary

AD=
Alzheimer disease;
ADC=
Alzheimer's Disease Center;
ADNC=
AD neuropathologic change;
CDR-SB=
Clinical Dementia Rating Dementia Staging Instrument Sum of Boxes;
CERAD=
Consortium to Establish a Registry for Alzheimer's Disease;
CI=
confidence interval;
FTLD=
frontotemporal lobar degeneration;
NACC=
National Alzheimer's Coordinating Center;
PART=
primary age-related tauopathy;
RR=
relative risk;
TDP-43=
TAR DNA-binding protein 43;
UDS=
Uniform Data Set;
VBI=
vascular brain injury

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 511

  • Received August 9, 2019.
  • Accepted in final form March 30, 2020.
  • © 2020 American Academy of Neurology
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