Presbycusis - age-related hearing loss - is an increasingly common communication disorder due to the aging and noisiness of our society.The prevalence and severity of presbycusis vary substantially in people of the same age and gender but the source(s) of this variability are incompletely understood. A major putative factor for this variability is heredity. The proposed research will continue our study of presbycusis using comprehensive examination methods to determine the inheritability of presbycusis in relation to its epidemiology and biomedical risk factors. We propose to: a) finish the auditory testing of the targeted members of the Framingham Offspring Group to determine the prevalence of presbycusis (as for their parents; b) delineate clinical presbycusis phenotypes in both groups; c) perform quantitative linkage analysis using the existing Genescan data base for the families with presbycusis pedigrees, d) perform complex segregation analysis of presbycusic families to assess the Mendelian inheritance patterns; and e) identity risk factors in families with genetic transmission. This is the first modern human study to assess the heritability of presbycusis. State-of-the-art methodology for auditory testing and genetic epidemiology are used. This research can only be done in a large parent-offspring group such as the Framingham Heart Study. Because the parents' hearing testing is done, and about 2/3 of the target Offspring will have been tested under the current funding, completion of this project will require testing of the remaining target Offspring during the first part of Offspring Study 7. Auditory tests are unchanged: pure-tone thresholds, immittance audiometry, acoustic impedance and reflectance, otoacoustic emissions, word recognition in quiet, Dichotic Digits test and the Synthetic Sentence Identification with Ipsilateral Competing Message. Presbycusis will be coded by: a) age-adjusted severity of loss; b) clinical pattern and phenotype, and c) whether it is of an early-onset type or not. Quantitative linkage analysis in the Genescan data base will examine the DNA of large families with presbycusis. Segregation analysis will be done for different phenotypes defined as: a) severity of presbycusis, b) presbycusis pattern, c) early-onset presbycusis, and d) co-variate adjusted models that will include known risk factors (gender, noise exposure, and cardiovascular diseases). Characterizing presbycusis by severity, age of onset, and clinical subtype will help to identify specific risk factors associated with hereditary presbycusis among genetically predisposed individuals. Identification of families with inherited presbycusis will facilitate future molecular genetic studies to identify genes for inherited defects.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
2R01DC001525-07A1
Application #
2853551
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1993-07-01
Project End
2002-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
7
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Washington
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Gates, George A; Anderson, Melissa L; McCurry, Susan M et al. (2011) Central auditory dysfunction as a harbinger of Alzheimer dementia. Arch Otolaryngol Head Neck Surg 137:390-5
Gates, George A; Gibbons, Laura E; McCurry, Susan M et al. (2010) Executive dysfunction and presbycusis in older persons with and without memory loss and dementia. Cogn Behav Neurol 23:218-23
Gates, George A; Anderson, Melissa L; Feeney, M Patrick et al. (2008) Central auditory dysfunction in older persons with memory impairment or Alzheimer dementia. Arch Otolaryngol Head Neck Surg 134:771-7
Gates, George A; Feeney, M Patrick; Mills, David (2008) Cross-sectional age-changes of hearing in the elderly. Ear Hear 29:865-74
Mills, David M; Feeney, M Patrick; Gates, George A (2007) Evaluation of cochlear hearing disorders: normative distortion product otoacoustic emission measurements. Ear Hear 28:778-92
Mills, David M (2006) Determining the cause of hearing loss: differential diagnosis using a comparison of audiometric and otoacoustic emission responses. Ear Hear 27:508-25
Cilento, Benjamin W; Norton, Susan J; Gates, George A (2003) The effects of aging and hearing loss on distortion product otoacoustic emissions. Otolaryngol Head Neck Surg 129:382-9
DeStefano, Anita L; Gates, George A; Heard-Costa, Nancy et al. (2003) Genomewide linkage analysis to presbycusis in the Framingham Heart Study. Arch Otolaryngol Head Neck Surg 129:285-9
Gates, George A; Feeney, M Patrick; Higdon, Roger J (2003) Word recognition and the articulation index in older listeners with probable age-related auditory neuropathy. J Am Acad Audiol 14:574-81
Gates, George A; Beiser, Alexa; Rees, Thomas S et al. (2002) Central auditory dysfunction may precede the onset of clinical dementia in people with probable Alzheimer's disease. J Am Geriatr Soc 50:482-8

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