PRESBYCUSIS--BIOMEDICAL RISK FACTORS

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Presbycusis is increasingly common due to the growing number of elderly in 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 have not been elucidated. A major, unexamined factor is heredity. The proposed projects will continue the study of presbycusis by using new examination methods and by determining the heritability of presbycusis in relation to its epidemiology and biomedical risk factors. We will estimate to what extent presbycusis is genetically determined and to what extent it results from acquired insults, both intrinsic and extrinsic. We propose to: a) perform a battery of auditory tests to determine the prevalence of presbycusis in members of the Framingham Offspring Group (as has been done for their parents enrolled in the Framingham Cohort Group); b) delineate clinical presbycusis subtypes (i.e. corresponding to the sensory, strial, neural, and cochlear conductive types of Schuknecht) in both groups; c) perform complex segregation analysis of presbycusis families to assess the Mendelian inheritance patterns for presbycusis; and d) identify risk factors in families with genetic transmission. This will be the first human study to document the heritability of presbycusis, and will employ state-of-the-art methodology for auditory testing and genetic epidemiology. This research can only be done in a large parent-offspring group such as the Framingham Study. Because hearing testing of the parents has been done, completion of this project will require testing only of their children during the 6th examination cycle of the Framingham Offspring Study. Auditory tests proposed are: pure tone thresholds, immittance audiometry, acoustic impedance and reflectance, otoacoustic emissions, world recognition in quiet and two central auditory tests, Dichotic Digits test, and Synthetic Sentence Identification with Ipsilateral Competing message. Multiple measures of hearing and auditory function are necessary to identify presbycusis subtypes. Presbycusis will be coded by a) severity of loss; b) whether it is an early-onset type; and c) clinical subtype. Cardiovascular and general health status data will be obtained as part of the Framingham Offspring Study, funded by a contract from the Nat'L. Heart Lung and Blood Inst. These data will be available for our analyses. Segregation analysis will be done for different phenotypes defined as; a) severity, b) early-onset, c) clinical subtype, and d) co-variate adjusted models including known risk factors (gender, noise exposure, and cardiovascular diseases). By characterizing presbycusis by severity, age of onset, and clinical subtype we hope to identify specific risk factors associated with hereditary presbycusis among genetically predisposed individuals. Identification of families with inherited presbycusis will facilitate future linkage studies and molecular genetic studies which can focus on the identification of genes responsible for inherited defects.