Age-Related Change in the Number of Neurons in the Human Vestibular Ganglion JOHN J. PARK, 1 YONG TANG, 1,2 IVAN LOPEZ, 1 AND AKIRA ISHIYAMA 1 * 1 Division of Head and Neck Surgery, UCLA School of Medicine, Los Angeles, California 90095 2 Department of Neurology, UCLA School of Medicine, Los Angeles, California 90095 ABSTRACT Dysequilibrium of aging in humans has been speculated to arise from progressive deterio- ration within anatomical components of the vestibular system. An integral part of this system is vestibular ganglions, which are bipolar neurons that relay peripheral vestibular information to the central nervous system. To assess the effect of aging on the number of human vestibular ganglion neurons, assumption-free stereology in the form of the optical fractionator was used on 20 serially sectioned archival human temporal bone specimens. Donors had no history of vestib- ular pathology and ranged in age from 2 to 88 years. An average of 25,812 (coefficient of variation = 0.13) vestibular ganglion neurons was found throughout this age range, a significant departure from the results of past studies. Logistics-based regression analysis pointed to a nonlinear pattern of decline in the neuronal population: the number of cells remained roughly constant at about 28,952 cells in youth and then declined gradually between 30 and 60 years of age before leveling off at approximately 23,349 cells in older individuals. This study confirmed the existence of an age-related decline in the primary neurons of the human vestibular system, thus providing one anatomical basis for the increased incidence of imbalance seen with age. J. Comp. Neurol. 431:437– 443, 2001. © 2001 Wiley-Liss, Inc. Indexing terms: stereology; optical fractionator; archival human temporal bone; Scarpa’s ganglia Dysequilibrium of aging refers to a progressive decline in motor skills along with mild episodic unsteadiness as a consequence of the aging vestibular system. The problem is commonly reported in an increasingly aging population, contributing to the high incidence of dizziness and falls. According to the National Ambulatory Medical Care Study, dizziness was the most common complaint in office practice among patients 75 years of age and older (Koch and Smith, 1985). Although some elderly patients suffer- ing from imbalance have known vestibular disorders, such as Menie `re’s disease, benign positional vertigo, and vas- cular disease affecting the vestibular system, a large per- centage of patients (ranging from 25% [Jenkins et al., 1989] to as high as 79% [Belal and Glorig, 1986]) cannot be categorized by a specific pathological diagnosis. Clinical tests of vestibular function have shown various degrees of age-related decline. Caloric testing by using warm and cold water irrigation into the ear canal showed only a modest decline in response with age (Mulch and Petermann, 1979). However, as pointed out by Jenkins et al. (1989) and Baloh et al. (1993), the caloric stimulus is nonphysiological and depends on multiple factors related to heat transfer and unrelated to vestibular function, such as ear canal volume, temporal bone thickness, and blood supply to the temporal bone. A more vestibular-specific test is rotational vestibular function testing, where re- flexes such as the vestibuloocular reflex (VOR) are mea- sured while the person sits in a chair rotating at various velocities. A large-scale cross-sectional study by Baloh et al. (1993) compared normal individuals over 75 years of age with individuals 18 –39 years of age. The study found a marked age-related decrease in VOR gain (peak velocity of the eyes relative to the peak velocity of the rotational chair), regardless of the amplitude of the rotational stim- ulus. These findings point to possible age-related deterio- ration in the sensory and neural pathways within the Grant sponsor: National Institutes of Health; Grant numbers: DC 00140-02 and AG 09693. *Correspondence to: Akira Ishiyama, Division of Head and Neck Sur- gery, UCLA School of Medicine, Los Angeles, CA 90095. E-mail: Ishiyama@ucla.edu Received 22 August 2000; Revised 5 December 2000; Accepted 11 De- cember 2000 THE JOURNAL OF COMPARATIVE NEUROLOGY 431:437– 443 (2001) © 2001 WILEY-LISS, INC.