Otology & Neurotology 36:260Y266 Ó 2015, Otology & Neurotology, Inc.
Association Between Saccular Function and Gait Speed: Data From the Baltimore Longitudinal Study of Aging *Andrew J. Layman, *Carol Li, †Eleanor Simonsick, †Luigi Ferrucci, *John P. Carey, and *Yuri Agrawal *Department of OtolaryngologyYHead and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore; and the ÞNational Institute on Aging, Longitudinal Studies Section, Harbor Hospital, Baltimore, Maryland, U.S.A.
Objective: To investigate whether otolith function (saccular and utricular) is associated with walking performance. Study Design: Cross-sectional analysis of observational data collected in the Baltimore Longitudinal Study of Aging. Setting: National Institute on Aging Intramural Research Program Clinical Research Unit at Harbor Hospital, Baltimore, Maryland. Patients: Community-dwelling participants. Intervention(s): Cervical and ocular vestibular evoked myogenic potentials (VEMPs) were used to assess saccular and utricular function, respectively. Main outcome measure(s): Cervical and ocular VEMP latency and amplitude responses and usual, rapid, and narrow (20 cm) gait speed assessed over a 6-m course. Results: In 314 participants (mean age, 73.1 yr; range, 26Y96 yr), cervical VEMP amplitude mediated the association between age
and gait speedVparticularly narrow walk speedVin both men and women. Cervical VEMP latency had an independent association with gait speed in age-, height-, and weight-adjusted analyses, although the direction of the association differed by sex. Greater cervical VEMP latency was associated with slower usual, rapid, and narrow gait speed in women but faster rapid gait speed in men. Neither the amplitude nor latency of ocular VEMP was associated with gait speed in men or women. Conclusion: These findings suggest that age-related slowing of gait speed is in part mediated by the decreased magnitude of saccular response associated with age. The sex-related differential association between saccular response latency and gait speed requires further study. Key Words: Vestibular evoked myogenic potentialsVAgingVGaitVVestibular dysfunction. Otol Neurotol 36:260Y266, 2015.
The vestibular system is responsible for sensing head orientation and acceleration, both at rest and in motion (1,2). Vestibular inputs are essential for stabilizing gaze (3) and the head (4,5) through vestibulo-ocular connections and trunk through vestibulo-spinal connections. Vestibular information particularly from the otolith organs (the saccule and the utricle) is critical for coordinating body movements aimed at maintaining dynamic balance especially during walking. Disorders of the vestibular system have been associated with gait abnormalities, including shorter stride length (6), slower gait speeds (7), and greater variation of stance, swing, and double support duration (8). Slower gait speed and greater gait variability in turn have been associated with increased fall risk and diminished survival, particularly in older populations (9,10). Although several cross-sectional (11Y20) and longitudinal (21) studies have reported age-related declines in
vestibular function, the impact of vestibular loss because of age on gait parameters has not been fully addressed. Previous studies have shown that head impulse testing, when used to screen for semicircular canal function in older individuals, is associated with slower gait speeds and increased fall risk (22). Yet the association between otolith function and functional gait parameters has not been fully investigated. The identification of vestibular evoked myogenic potentials (VEMPs) and the characterization of different stimulus and response parameters have made possible the independent assessment of saccular versus utricular function. Air-conducted cervical VEMP (cVEMP) and bone vibration conducted ocular VEMP (oVEMP) have been described as measures of saccular and utricular function, respectively (23). In this study, we investigated the crosssectional associations between saccular and utricular function and gait speed under three conditions (usual, rapid, and narrow) in a cohort of community volunteers aged 26 to 98 years who participated in an ongoing longitudinal study. Assessing gait under different conditions allows investigation of the association between otolith function and gait with increased vertical displacement (rapid gait) and decreased base of support (narrow gait). Thus, this study
Address correspondence and reprint requests to Yuri Agrawal, M.D., 601 North Caroline St, Johns Hopkins Outpatient Center, Baltimore, MD 21287, U.S.A.; E-mail: [email protected] This study was supported by the National Institutes of Health, the American Otological Society Clinician Scientist Award, and the NIA Older Americans Independence Center Research Career Development Core grant. The authors disclose no conflicts of interest.
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SACCULAR FUNCTION AND GAIT SPEED aimed to measure VEMP and gait characteristics in a community-dwelling population across the age range to determine the relationship between otolith function and the age-associated slowing of gait speed. MATERIALS AND METHODS This study was conducted as part of the Baltimore Longitudinal Study of Aging (BLSA), a longitudinal observational study initiated in 1958 to evaluate normative aging with eligibility at enrollment restricted to persons free of cognitive impairment, functional limitations, chronic diseases, and cancer within the past 10 years. Once enrolled, participants are followed until death through regularly scheduled comprehensive health, cognitive, and functional evaluations that take place over a three-day visit to the National Institute on Aging Intramural Research Program Clinical Research Unit at Harbor Hospital, Baltimore, Maryland.
261 Gait Testing
Gait data were collected as part of the extended Short Physical Performance Battery (24). All gait speeds were hand-timed across a 6-m course. Two trials each were administered for usual and rapid gait tests with the fastest of each trial used in the analyses. Participants were asked to complete the course at their usual walking speed before being asked to attempt the course at their fastest possible speed. For the narrow walk, participants were instructed to walk only within a marked 20-cm wide path. Touching or crossing the marked boundaries two or more times resulted in a failed attempt. Three attempts were permitted with the fastest of any successful attempts used in the analyses. Participants unable to complete the gait courses without assistance were excluded from the analyses.
Covariates Height in centimeters and weight in kilograms were assessed for all participants at each study visit and were included in analyses because of their known associations with gait speed.
Participants Data for this study come from BLSA participants who had their regular clinic visit between February 2013 and September 2013 and underwent both cVEMP and oVEMP testing and completed a standardized physical performance battery that included usual, rapid, and narrow gait speed assessment without using a walking aid. Participants were excluded from oVEMP testing if they could not participate in the calibration procedures because of blindness. Exclusion criteria for cVEMP testing included conductive hearing loss or the inability to maintain a flexed sternocleidomastoid muscle during the testing interval. Information on participant age and gender was also collected.
VEMP Testing VEMP testing was conducted using a commercial electromyographic system (Medelec Synergy, software version 14.1; Care Fusion, Dublin, OH, USA). Cervical VEMPs were elicited using monoaural air-conducted 500-Hz (125 dB SPL) tone bursts at a rate of 5 pulses per second delivered for 20 seconds through over-the-ear headphones (Viasys Healthcare, Madison, WI, USA). Recording electrodes were placed along the ipsilateral sternocleidomastoid belly and the sternoclavicular junction as well as a ground electrode on the sternum. Participants were placed in the supine position, with their upper bodies elevated 30 degrees above the horizontal and were asked to actively flex their neck by raising their heads just before testing. The beginning of the cVEMP response was identified as the maximal positive deflection between 11 and 15 milliseconds after the onset of the stimulus, with the subsequent maximal negative deflection indicating the end of the response. Peak-to-peak amplitudes were corrected for the background electromyographic activity (940 KV) recorded just before stimulus onset. Ocular VEMPS were elicited using manual taps delivered to the hairline in the midline using a reflex hammer with an inertial trigger (VIASYS Healthcare). The first recording electrode was centered 2 cm below the pupil, with the second located 0.5 cm below the edge of the first. Electrode placement and symmetry were checked with 20-degree vertical saccades (G25% asymmetry) before testing. During administration of the stimulus, the participants were instructed to fix their gaze at a target 30 degrees above their normal gaze position. The beginning of the oVEMP response was identified as the maximal negative peak occurring 5 to 10 milliseconds after the onset of the stimulus, with the subsequent maximal positive deflection indicating the end of the response.
Statistical Analysis Left- and right-sided responses were correlated within each participant, with correlation coefficients as follows: oVEMP latency (r = 0.666, p = 0.000); oVEMP amplitude (r = 0.986, p G 0.001); cVEMP latency (r = 0.432, p G 0.001); and cVEMP amplitude (r = 0.665, p G 0.001). Thus, right- and left-sided responses were averaged for analysis. In the absence of a VEMP response, the amplitude was assigned a value of zero, whereas for latency analysis, an absent VEMP response was treated as missing data. Participants with unilateral VEMP losses were excluded from analysis. Multiple linear regression analysis was used to evaluate the association between VEMP predictor variables and gait speed outcome variables adjusted for age. All results were considered significant at the level of p G 0.05. Stata/SE version 12.0 (StataCorp, College Station, TX, USA) was used for statistical analysis.
RESULTS Demographics A sample of 314 participants from the BLSA underwent VEMP testing and was available for analysis. The mean age of this sample was 73.1 years (SD, 12.8; range, 26Y96 yr). Men comprised 45.2% of the sample. Among women, mean (SD) for height was 160.7 cm (6.2), and mean (SD) for weight was 68.2 kg (14.1). Among men, mean (SD) for height was 173.9 cm (7.6), and mean (SD) for weight was 83.3 kg (15.7). Otolith Function and Aging Consistent with prior studies, we observed significant trends in VEMP amplitude and latency associated with increasing age. Trends varied between men and women; therefore, analyses are presented separately by gender. Ocular VEMP latency increased with age in men (A = 0.022 ms/year; p G 0.001) but did not vary with age in women (A = 0.002 ms/year; p = 0.661); the age-bygender interaction term was significant (p = 0.013). Ocular VEMP ˙ peak-to-peak amplitude was lower for both men (A = Y0.299 KV/year; p G 0.001) and women (A = Y0.312 KV/year; p G 0.001) with increasing age Otology & Neurotology, Vol. 36, No. 2, 2015
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FIG. 1. Effect of aging on ocular vestibular-evoked myogenic potential (oVEMP) latency and amplitude. Ocular VEMP latencies significantly increased only in men (p G 0.05). Cervical VEMP amplitudes decreased significantly for both men and women with age (p G 0.05).
(Fig. 1). Cervical VEMP latency did not vary with age for either men (A = 0.012 ms/year; p = 0.322) or women (A = 0.002 ms/year; p = 0.180), whereas cVEMP peakto-peak amplitude was lower with increasing age for both men (A = Y0.034 units/year; p = 0.000) and women (A = Y0.029 units/year; p = 0.001) (Fig. 2).
Gait Speed and Aging Gait speed was slower with increasing age for usual, rapid, and narrow walks (A = Y0.0087 m/s/year; p G 0.0001; A = Y0.016 m/s/year; p G 0.0001; A = Y0.0091 m/s/year; p G 0.0001, respectively). Because there were no differences in age-related slowing between men and women for
FIG. 2. Effect of aging on cervical vestibular-evoked myogenic potential (cVEMP) amplitude and latency. Cervical VEMP latency was not significant for either men or women. Cervical VEMP amplitude significantly decreased with age for both men and women (p G 0.05). Otology & Neurotology, Vol. 36, No. 2, 2015
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SACCULAR FUNCTION AND GAIT SPEED
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FIG. 3. Effect of aging on gait speed for three different gait types. Significant associations between age and gait speed were observed for all three gait types (p G 0.05).
usual gait speed ( p interaction term = 0.838), rapid gait speed ( p interaction term = 0.236), or narrow walk gait speed ( p interaction term = 0.826), aggregate data across gender are presented (Fig. 3). Associations Between Otolith Function and Gait Speed We next evaluated associations between VEMP and gait speed in analyses adjusted for age, height in centimeters, and weight in kilograms (Table 1). We ran a series of regression models to evaluate whether cervical and ocular VEMP amplitude and latency mediate the association between age and gait speed. For a variable to be considered a mediator: 1) the mediator must be associated with the predictor variable; 2) the mediator must be associated with the outcome, and 3) when both mediator and predictor variable are included in the model simultaneously, the association between the predictor and outcome variable is greatly attenuated or eliminated (25). In Model 1, we evaluated the association between age and gait speed adjusting only for height and weight. In Model 2, we added the VEMP amplitude or latency variable and evaluated the coefficients associated with the age term and the VEMP term. We observed that cVEMP amplitude partially mediated the association between age and usual gait, rapid gait, and narrow walk speed (Table 1). When cVEMP amplitude was added to the regression model for usual gait speed, the effect of age decreased by 23% (from A = Y0.00882 m/s/year to A = Y0.00679 m/s/year). When cVEMP amplitude was added to the regression model for rapid gait speed, the effect of age decreased by 25% (from A = Y0.01487 m/s/year to A = Y0.01114 m/s/year). When cVEMP amplitude was added to the regression model for narrow walk gait speed, the effect of age decreased by 39% (from A = Y0.00890 m/s/year to A = Y0.00542 m/s/year),
and cVEMP amplitude was also independently associated with narrow walk gait speed (A = 0.09608 m/s/year; p = 0.0078). We analyzed cVEMP latency separately for men and women because the association between age and cVEMP latency differed significantly by gender. cVEMP latency did not appear to mediate the association between age and gait speed in both men and women; the association between age and gait speed did not change appreciably with the addition of cVEMP latency into the models (Table 2). cVEMP latency did have an independent association with gait speed after adjustment for age, particularly in women. In women, longer cVEMP latency was associated with slower usual (A = Y0.05251; p = 0.0197), rapid (A = Y0.0934; p = 0.006), and narrow walk (A = Y0.07975; p = 0.014) gait speeds. In men, longer cVEMP latency predicted faster rapid gait speed (A = 0.12693; p = 0.0158), but was not significantly associated with usual or narrow walk gait speed.
Regression models of cVEMP amplitude and gait speed
TABLE 1. Gait Usual Rapid Narrow
Model
Aage
P Value
1 2 1 2 1 2
j0.00882 j0.00679 j0.01487 j0.01114 j0.00890 j0.00542
G0.0001 0.0002 G0.0001 0.0003 G0.0001 0.0262
Ac_amp
P Value
0.02127
0.4190
0.06855
0.1230
0.09608
0.0078
cVEMP indicates cervical vestibular-evoked myogenic potential; Model 1, age only; Model 2, age and cVEMP amplitude or latency; Aage, the change in gait speed associated with each 1-year increase in age; Ac_amp, the change in gait speed associated with each 1-unit increase in cVEMP amplitude. Otology & Neurotology, Vol. 36, No. 2, 2015
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A. J. LAYMAN ET AL. Regression models of cVEMP latency and gait speed by gender
TABLE 2. Gait
Model
Aage
P Value
1 2 1 2 1 2
j0.00541 j0.00508 j0.01488 j0.01429 j0.00888 j0.00823
0.0295 0.0333 0.0002 0.0001 0.0103 0.0127
1 2 1 2 1 2
j0.00874 j0.00906 j0.01690 j0.01823 j0.00802 j0.00816
0.0038 0.0030 0.0017 0.0005 0.0576 0.0578
Women Usual
Ac_lat
P Value
Narrow Men Usual Rapid Narrow
j0.0525
0.0197
Rapid
j0.0934
0.0061
Narrow
j0.0798
0.0137
0.03045
0.3201
0.12693
0.0158
0.01242
0.7790
cVEMP indicates cervical vestibular-evoked myogenic potential; Model 1, age only; Model 2, age and cVEMP amplitude or latency; Aage, the change in gait speed associated with each 1-year increase in age; Ac_lat, the change in gait speed associated with each 1-millisecond increase in cVEMP latency.
Neither oVEMP amplitude nor latency appeared to be a mediator of the association between age and gait speed, or had significant independent associations with gait speed in age-adjusted analyses (Tables 3 and 4). DISCUSSION This study evaluated the association between otolith function and age-associated slowing of gait speed. Although previous studies have collected VEMP data in aging populations (22), these data have not been linked to gait performance. Studies that have evaluated the relationship between vestibular function and gait have largely focused on tests of semicircular canal function such as head-impulse testing (24) or head-shake tests (8). Our analysis suggests that impaired saccular function may impact gait speed. Specifically, we found that saccular response magnitude partially mediates the association between age and gait speed, and saccular response timing independently predicts gait speed, and the direction of this latter association differs by sex. The saccular response has two dimensions: magnitude and timing. The magnitude or strength of the response, Regression models of oVEMP amplitude and gait speed
TABLE 3. Gait
Rapid Narrow
Gait Usual
Rapid
Usual
TABLE 4.
Model
Aage
P Value
1 2 1 2 1 2
j0.0101 j0.0098 j0.0166 j0.0156 j0.0093 j0.0098
G0.0001 G0.0001 G0.0001 G0.0001 G0.0001 0.0019
Ao_amp
P Value
j0.0016
0.411
j0.002
0.4957
j0.0015
0.5532
oVEMP indicates ocular vestibular-evoked myogenic potential; Model 1, age only; Model 2, age and oVEMP amplitude or latency; Aage, the change in gait speed associated with each 1-year increase in age; Ao_amp, the change in gait speed associated with each 1-KV increase in oVEMP amplitude.
Regression models of oVEMP latency and gait speed
Model
Aage
P Value
1 2 1 2 1 2
j0.0093 j0.0091 j0.015 j0.0146 j0.0082 j0.0082
G0.0001 G0.0001 G0.0001 G0.0001 G0.0001 G0.0001
Ao_lat
P Value
j0.0124
0.6318
j0.0277
0.493
0.00488
0.8399
oVEMP indicates ocular vestibular-evoked myogenic potential; Model 1, age only; Model 2, age and oVEMP amplitude or latency; Aage, the change in gait speed associated with each 1-year increase in age; Ao_lat, the change in gait speed associated with each 1-millisecond increase in oVEMP latency.
measured by cVEMP amplitude, has been consistently shown to decrease with age (17,19,28). We observed that the association between age and declining gait speed was partially mediated by the decline in cVEMP amplitude with age. Prior studies suggest an important role for the saccule during locomotion (4,5). Vertical linear accelerations in the sagittal plane during locomotion generate shearing forces within the vertically oriented saccular macula, resulting in increased saccular signaling. Saccular signaling may then contribute to head stabilization and postural stabilization during gait via sacculo-collic and sacculospinal reflexes. As such, reduced saccular sensitivity may lead to destabilization and compensatory slowing of gait. Interestingly, direction of association between saccular latency and gait speed appear to differ between men and women. In the presence of increased saccular latency, men have faster gait speeds, whereas women have lower gait speeds. Studies suggest that the adoption of a rapid gait confers greater stability in patients with a vestibulopathy because automated spinal locomotion overrides the vestibular inputs (27,28). However, the advantages associated with a more rapid gait may not be the same for men and women because of differences in hip geometry, body composition (e.g., muscle mass), or center of mass. The different strategies in men and women may alternatively be attributable to a difference in the sensitivity of the saccule to vertical linear displacement between men and women. Although absolute vertical head displacement is larger in men, when corrected for leg length, men and women experience the same relative head bob during gait (29). If the size of the saccule is conserved between men and women, the smaller absolute displacement experienced by women may lead to decreased saccular signaling compared with men. The adoption of gender-specific gait strategies in response to a physiologic impairment has been observed previously. For example, studies have shown that men and women adopt different gait strategies in response to osteoarthritis, with faster and longer leg swings and decreased single-support time being observed in men (30). We present a conceptual causal model of the association between the two dimensions of saccular function (magnitude and timing) and aging and gait speed (Fig. 4). The magnitude of the saccular response appears to partially mediate the association between age and gait speed,
Otology & Neurotology, Vol. 36, No. 2, 2015
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SACCULAR FUNCTION AND GAIT SPEED
FIG. 4.
265
Conceptual model for association among age, saccular responses magnitude, saccular response timing, and gait speed.
whereas the timing of the saccular response has an independent influence on gait speed. Of note, we did not observe any association between utricular function and gait speed, as evidenced by non-significant oVEMP correlations with gait speed in these data. This may reflect the anatomy and physiology of the utricle. The utricular maculi are horizontally oriented, and are most responsive to head tilt and horizontal translation. Thus utricular dysfunction may not affect gait as markedly as a dysfunction of the saccule. Several limitations of this study should be noted. The participants of this study represent a generally healthy population who are available to travel and are committed to recurrent visits for several decades. Thus, our findings may not be applicable to the general population and in particular to people affected by substantial morbidity. Moreover, we only considered gait speed in this study, and speed is only one performance dimension of gait. Ongoing analyses are currently examining kinematic data from a three-dimensional motion capture system to more fully characterize gait characteristics (e.g., joint movements, center of mass sway) of individuals with decreased otolith and semicircular canal function. However, such measurements may not be readily available to the clinician, making them less practical as a diagnostic or evaluative measure. Finally, our analyses adjusted for age, as a surrogate for age-related losses of other sensory and motor functions that influence gait function. There is a possibility of residual confounding by sensory or motor impairment not captured by the age variable alone. This study confirms age-associated declines in both otolith function and gait speed. These findings further suggest that age-related declines in saccular response magnitude partially mediate the association between age and gait speed in a cohort of community-dwelling individuals. Additionally, these data suggest saccular response latency is an independent predictor of gait speed, and that men and women with increased saccular response latency make opposite adjustments to their gait: men increase gait speed while women decrease gait speed. REFERENCES 1. Horak FB, Shupert CL, Dietz V, et al. Vestibular and somatosensory contributions to responses to head and body displacements in stance. Exp Brain Res 1994;100:93Y106. 2. Goldberg JM. The Vestibular System: A Sixth Sense. Oxford, NY: Oxford University Press, 2012:xiii, 541 p.
3. Whitney SL, Marchetti GF, Pritcher M, et al. Gaze stabilization and gait performance in vestibular dysfunction. Gait Posture 2009; 29:194Y8. 4. Pozzo T, Berthoz A, Lefort L, et al. Head stabilization during various locomotor tasks in humans. II. Patients with bilateral peripheral vestibular deficits. Exp Brain Res 1991;85:208Y17. 5. Pozzo T, Berthoz A, Vitte E, et al. Head stabilization during locomotion. Perturbations induced by vestibular disorders. Acta Otolaryngol Suppl 1991;481:322Y7. 6. Lang J, Ishikawa K, Hatakeyama K, et al. 3D body segment oscillation and gait analysis for vestibular disorders. Auris Nasus Larynx 2013;40:18Y24. 7. Roberts JC, Cohen HS, Sangi-Haghpeykar H. Vestibular disorders and dual task performance: impairment when walking a straight path. J Vestib Res 2011;21:167Y74. 8. Angunsri N, Ishikawa K, Yin M, et al. Gait instability caused by vestibular disorders - analysis by tactile sensor. Auris Nasus Larynx 2011;38:462Y8. 9. Studenski S, Perera S, Patel K, et al. Gait speed and survival in older adults. JAMA 2011;305:50Y8. 10. Schrager MA, Kelly VE, Price R, et al. The effects of age on mediolateral stability during normal and narrow base walking. Gait Posture 2008;28:466Y71. 11. Peterka RJ, Black FO. Age-related changes in human posture control: sensory organization tests. J Vestib Res 1990;1:73Y85. 12. Peterka RJ, Black FO, Schoenhoff MB. Age-related changes in human vestibulo-ocular and optokinetic reflexes: pseudorandom rotation tests. J Vestib Res 1990;1:61Y71. 13. Peterka RJ, Black FO, Schoenhoff MB. Age-related changes in human vestibulo-ocular reflexes: sinusoidal rotation and caloric tests. J Vestib Res 1990;1:49Y59. 14. Nguyen KD, Welgampola MS, Carey JP. Test-retest reliability and age-related characteristics of the ocular and cervical vestibular evoked myogenic potential tests. Otol Neurotol 2010; 31:793Y802. 15. Welgampola MS, Colebatch JG. Vestibulocollic reflexes: normal values and the effect of age. Clin Neurophysiol 2001;112:1971Y9. 16. Welgampola MS, Colebatch JG. Selective effects of ageing on vestibular-dependent lower limb responses following galvanic stimulation. Clin Neurophysiol 2002;113:528Y34. 17. Brantberg K, Granath K, Schart N. Age-related changes in vestibular evoked myogenic potentials. Audiol Neurootol 2007;12: 247Y53. 18. Paige GD. Senescence of human visual-vestibular interactions. 1. Vestibulo-ocular reflex and adaptive plasticity with aging. J Vestib Res 1992;2:133Y51. 19. Paige GD. Senescence of human visual-vestibular interactions: smooth pursuit, optokinetic, and vestibular control of eye movements with aging. Exp Brain Res 1994;98:355Y72. 20. Agrawal Y, Zuniga MG, Davalos-Bichara M, et al. Decline in semicircular canal and otolith function with age. Otol Neurotol 2012; 33:832Y9. 21. Baloh RW, Enrietto J, Jacobson KM, et al. Age-related changes in vestibular function: a longitudinal study. Ann N Y Acad Sci 2001; 942:210Y9. Otology & Neurotology, Vol. 36, No. 2, 2015
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22. Agrawal Y, Davalos-Bichara M, Zuniga MG, et al. Head impulse test abnormalities and influence on gait speed and falls in older individuals. Otol Neurotol 2013;34:1729Y35. 23. Welgampola MS, Carey JP. Waiting for the evidence: VEMP testing and the ability to differentiate utricular versus saccular function. Otolaryngol Head Neck Surg 2010;143:281Y3. 24. Simonsick EM, Newman AB, Nevitt MC, et al. Measuring higher level physical function in well-functioning older adults: expanding familiar approaches in the Health ABC study. J Gerontol A Biol Sci Med Sci 2001;56:M644Y9. 25. Baron RM, Kenny DA. The moderator-mediator variable distinction insocial psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol 1986;51:1173Y82.
26. Basta D, Todt I, Ernst A. Normative data for P1/N1-latencies of vestibular evoked myogenic potentials induced by air- or boneconducted tone bursts. Clin Neurophysiol 2005;116:2216Y9. 27. Jahn K, Strupp M, Schneider E, et al. Differential effects of vestibular stimulation on walking and running. Neuroreport 2000;11:1745Y8. 28. Brandt T, Strupp M, Benson J. You are better off running than walking with acute vestibulopathy. Lancet 1999;354:746. 29. Senden R, Grimm B, Heyligers IC, et al. Acceleration-based gait test for healthy subjects: reliability and reference data. Gait Posture 2009;30:192Y6. 30. Debi R, Mor A, Segal O, et al. Differences in gait patterns, pain, function and quality of life between males and females with knee osteoarthritis: a clinical trial. BMC Musculoskelet Disord 2009;10:127.
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Association Between Saccular Function and Gait Speed: Data From the Baltimore Longitudinal Study of Aging *Andrew J. Layman, *Carol Li, †Eleanor Simonsick, †Luigi Ferrucci, *John P. Carey, and *Yuri Agrawal *Department of OtolaryngologyYHead and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore; and the ÞNational Institute on Aging, Longitudinal Studies Section, Harbor Hospital, Baltimore, Maryland, U.S.A.
Objective: To investigate whether otolith function (saccular and utricular) is associated with walking performance. Study Design: Cross-sectional analysis of observational data collected in the Baltimore Longitudinal Study of Aging. Setting: National Institute on Aging Intramural Research Program Clinical Research Unit at Harbor Hospital, Baltimore, Maryland. Patients: Community-dwelling participants. Intervention(s): Cervical and ocular vestibular evoked myogenic potentials (VEMPs) were used to assess saccular and utricular function, respectively. Main outcome measure(s): Cervical and ocular VEMP latency and amplitude responses and usual, rapid, and narrow (20 cm) gait speed assessed over a 6-m course. Results: In 314 participants (mean age, 73.1 yr; range, 26Y96 yr), cervical VEMP amplitude mediated the association between age
and gait speedVparticularly narrow walk speedVin both men and women. Cervical VEMP latency had an independent association with gait speed in age-, height-, and weight-adjusted analyses, although the direction of the association differed by sex. Greater cervical VEMP latency was associated with slower usual, rapid, and narrow gait speed in women but faster rapid gait speed in men. Neither the amplitude nor latency of ocular VEMP was associated with gait speed in men or women. Conclusion: These findings suggest that age-related slowing of gait speed is in part mediated by the decreased magnitude of saccular response associated with age. The sex-related differential association between saccular response latency and gait speed requires further study. Key Words: Vestibular evoked myogenic potentialsVAgingVGaitVVestibular dysfunction. Otol Neurotol 36:260Y266, 2015.
The vestibular system is responsible for sensing head orientation and acceleration, both at rest and in motion (1,2). Vestibular inputs are essential for stabilizing gaze (3) and the head (4,5) through vestibulo-ocular connections and trunk through vestibulo-spinal connections. Vestibular information particularly from the otolith organs (the saccule and the utricle) is critical for coordinating body movements aimed at maintaining dynamic balance especially during walking. Disorders of the vestibular system have been associated with gait abnormalities, including shorter stride length (6), slower gait speeds (7), and greater variation of stance, swing, and double support duration (8). Slower gait speed and greater gait variability in turn have been associated with increased fall risk and diminished survival, particularly in older populations (9,10). Although several cross-sectional (11Y20) and longitudinal (21) studies have reported age-related declines in
vestibular function, the impact of vestibular loss because of age on gait parameters has not been fully addressed. Previous studies have shown that head impulse testing, when used to screen for semicircular canal function in older individuals, is associated with slower gait speeds and increased fall risk (22). Yet the association between otolith function and functional gait parameters has not been fully investigated. The identification of vestibular evoked myogenic potentials (VEMPs) and the characterization of different stimulus and response parameters have made possible the independent assessment of saccular versus utricular function. Air-conducted cervical VEMP (cVEMP) and bone vibration conducted ocular VEMP (oVEMP) have been described as measures of saccular and utricular function, respectively (23). In this study, we investigated the crosssectional associations between saccular and utricular function and gait speed under three conditions (usual, rapid, and narrow) in a cohort of community volunteers aged 26 to 98 years who participated in an ongoing longitudinal study. Assessing gait under different conditions allows investigation of the association between otolith function and gait with increased vertical displacement (rapid gait) and decreased base of support (narrow gait). Thus, this study
Address correspondence and reprint requests to Yuri Agrawal, M.D., 601 North Caroline St, Johns Hopkins Outpatient Center, Baltimore, MD 21287, U.S.A.; E-mail: [email protected] This study was supported by the National Institutes of Health, the American Otological Society Clinician Scientist Award, and the NIA Older Americans Independence Center Research Career Development Core grant. The authors disclose no conflicts of interest.
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SACCULAR FUNCTION AND GAIT SPEED aimed to measure VEMP and gait characteristics in a community-dwelling population across the age range to determine the relationship between otolith function and the age-associated slowing of gait speed. MATERIALS AND METHODS This study was conducted as part of the Baltimore Longitudinal Study of Aging (BLSA), a longitudinal observational study initiated in 1958 to evaluate normative aging with eligibility at enrollment restricted to persons free of cognitive impairment, functional limitations, chronic diseases, and cancer within the past 10 years. Once enrolled, participants are followed until death through regularly scheduled comprehensive health, cognitive, and functional evaluations that take place over a three-day visit to the National Institute on Aging Intramural Research Program Clinical Research Unit at Harbor Hospital, Baltimore, Maryland.
261 Gait Testing
Gait data were collected as part of the extended Short Physical Performance Battery (24). All gait speeds were hand-timed across a 6-m course. Two trials each were administered for usual and rapid gait tests with the fastest of each trial used in the analyses. Participants were asked to complete the course at their usual walking speed before being asked to attempt the course at their fastest possible speed. For the narrow walk, participants were instructed to walk only within a marked 20-cm wide path. Touching or crossing the marked boundaries two or more times resulted in a failed attempt. Three attempts were permitted with the fastest of any successful attempts used in the analyses. Participants unable to complete the gait courses without assistance were excluded from the analyses.
Covariates Height in centimeters and weight in kilograms were assessed for all participants at each study visit and were included in analyses because of their known associations with gait speed.
Participants Data for this study come from BLSA participants who had their regular clinic visit between February 2013 and September 2013 and underwent both cVEMP and oVEMP testing and completed a standardized physical performance battery that included usual, rapid, and narrow gait speed assessment without using a walking aid. Participants were excluded from oVEMP testing if they could not participate in the calibration procedures because of blindness. Exclusion criteria for cVEMP testing included conductive hearing loss or the inability to maintain a flexed sternocleidomastoid muscle during the testing interval. Information on participant age and gender was also collected.
VEMP Testing VEMP testing was conducted using a commercial electromyographic system (Medelec Synergy, software version 14.1; Care Fusion, Dublin, OH, USA). Cervical VEMPs were elicited using monoaural air-conducted 500-Hz (125 dB SPL) tone bursts at a rate of 5 pulses per second delivered for 20 seconds through over-the-ear headphones (Viasys Healthcare, Madison, WI, USA). Recording electrodes were placed along the ipsilateral sternocleidomastoid belly and the sternoclavicular junction as well as a ground electrode on the sternum. Participants were placed in the supine position, with their upper bodies elevated 30 degrees above the horizontal and were asked to actively flex their neck by raising their heads just before testing. The beginning of the cVEMP response was identified as the maximal positive deflection between 11 and 15 milliseconds after the onset of the stimulus, with the subsequent maximal negative deflection indicating the end of the response. Peak-to-peak amplitudes were corrected for the background electromyographic activity (940 KV) recorded just before stimulus onset. Ocular VEMPS were elicited using manual taps delivered to the hairline in the midline using a reflex hammer with an inertial trigger (VIASYS Healthcare). The first recording electrode was centered 2 cm below the pupil, with the second located 0.5 cm below the edge of the first. Electrode placement and symmetry were checked with 20-degree vertical saccades (G25% asymmetry) before testing. During administration of the stimulus, the participants were instructed to fix their gaze at a target 30 degrees above their normal gaze position. The beginning of the oVEMP response was identified as the maximal negative peak occurring 5 to 10 milliseconds after the onset of the stimulus, with the subsequent maximal positive deflection indicating the end of the response.
Statistical Analysis Left- and right-sided responses were correlated within each participant, with correlation coefficients as follows: oVEMP latency (r = 0.666, p = 0.000); oVEMP amplitude (r = 0.986, p G 0.001); cVEMP latency (r = 0.432, p G 0.001); and cVEMP amplitude (r = 0.665, p G 0.001). Thus, right- and left-sided responses were averaged for analysis. In the absence of a VEMP response, the amplitude was assigned a value of zero, whereas for latency analysis, an absent VEMP response was treated as missing data. Participants with unilateral VEMP losses were excluded from analysis. Multiple linear regression analysis was used to evaluate the association between VEMP predictor variables and gait speed outcome variables adjusted for age. All results were considered significant at the level of p G 0.05. Stata/SE version 12.0 (StataCorp, College Station, TX, USA) was used for statistical analysis.
RESULTS Demographics A sample of 314 participants from the BLSA underwent VEMP testing and was available for analysis. The mean age of this sample was 73.1 years (SD, 12.8; range, 26Y96 yr). Men comprised 45.2% of the sample. Among women, mean (SD) for height was 160.7 cm (6.2), and mean (SD) for weight was 68.2 kg (14.1). Among men, mean (SD) for height was 173.9 cm (7.6), and mean (SD) for weight was 83.3 kg (15.7). Otolith Function and Aging Consistent with prior studies, we observed significant trends in VEMP amplitude and latency associated with increasing age. Trends varied between men and women; therefore, analyses are presented separately by gender. Ocular VEMP latency increased with age in men (A = 0.022 ms/year; p G 0.001) but did not vary with age in women (A = 0.002 ms/year; p = 0.661); the age-bygender interaction term was significant (p = 0.013). Ocular VEMP ˙ peak-to-peak amplitude was lower for both men (A = Y0.299 KV/year; p G 0.001) and women (A = Y0.312 KV/year; p G 0.001) with increasing age Otology & Neurotology, Vol. 36, No. 2, 2015
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FIG. 1. Effect of aging on ocular vestibular-evoked myogenic potential (oVEMP) latency and amplitude. Ocular VEMP latencies significantly increased only in men (p G 0.05). Cervical VEMP amplitudes decreased significantly for both men and women with age (p G 0.05).
(Fig. 1). Cervical VEMP latency did not vary with age for either men (A = 0.012 ms/year; p = 0.322) or women (A = 0.002 ms/year; p = 0.180), whereas cVEMP peakto-peak amplitude was lower with increasing age for both men (A = Y0.034 units/year; p = 0.000) and women (A = Y0.029 units/year; p = 0.001) (Fig. 2).
Gait Speed and Aging Gait speed was slower with increasing age for usual, rapid, and narrow walks (A = Y0.0087 m/s/year; p G 0.0001; A = Y0.016 m/s/year; p G 0.0001; A = Y0.0091 m/s/year; p G 0.0001, respectively). Because there were no differences in age-related slowing between men and women for
FIG. 2. Effect of aging on cervical vestibular-evoked myogenic potential (cVEMP) amplitude and latency. Cervical VEMP latency was not significant for either men or women. Cervical VEMP amplitude significantly decreased with age for both men and women (p G 0.05). Otology & Neurotology, Vol. 36, No. 2, 2015
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SACCULAR FUNCTION AND GAIT SPEED
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FIG. 3. Effect of aging on gait speed for three different gait types. Significant associations between age and gait speed were observed for all three gait types (p G 0.05).
usual gait speed ( p interaction term = 0.838), rapid gait speed ( p interaction term = 0.236), or narrow walk gait speed ( p interaction term = 0.826), aggregate data across gender are presented (Fig. 3). Associations Between Otolith Function and Gait Speed We next evaluated associations between VEMP and gait speed in analyses adjusted for age, height in centimeters, and weight in kilograms (Table 1). We ran a series of regression models to evaluate whether cervical and ocular VEMP amplitude and latency mediate the association between age and gait speed. For a variable to be considered a mediator: 1) the mediator must be associated with the predictor variable; 2) the mediator must be associated with the outcome, and 3) when both mediator and predictor variable are included in the model simultaneously, the association between the predictor and outcome variable is greatly attenuated or eliminated (25). In Model 1, we evaluated the association between age and gait speed adjusting only for height and weight. In Model 2, we added the VEMP amplitude or latency variable and evaluated the coefficients associated with the age term and the VEMP term. We observed that cVEMP amplitude partially mediated the association between age and usual gait, rapid gait, and narrow walk speed (Table 1). When cVEMP amplitude was added to the regression model for usual gait speed, the effect of age decreased by 23% (from A = Y0.00882 m/s/year to A = Y0.00679 m/s/year). When cVEMP amplitude was added to the regression model for rapid gait speed, the effect of age decreased by 25% (from A = Y0.01487 m/s/year to A = Y0.01114 m/s/year). When cVEMP amplitude was added to the regression model for narrow walk gait speed, the effect of age decreased by 39% (from A = Y0.00890 m/s/year to A = Y0.00542 m/s/year),
and cVEMP amplitude was also independently associated with narrow walk gait speed (A = 0.09608 m/s/year; p = 0.0078). We analyzed cVEMP latency separately for men and women because the association between age and cVEMP latency differed significantly by gender. cVEMP latency did not appear to mediate the association between age and gait speed in both men and women; the association between age and gait speed did not change appreciably with the addition of cVEMP latency into the models (Table 2). cVEMP latency did have an independent association with gait speed after adjustment for age, particularly in women. In women, longer cVEMP latency was associated with slower usual (A = Y0.05251; p = 0.0197), rapid (A = Y0.0934; p = 0.006), and narrow walk (A = Y0.07975; p = 0.014) gait speeds. In men, longer cVEMP latency predicted faster rapid gait speed (A = 0.12693; p = 0.0158), but was not significantly associated with usual or narrow walk gait speed.
Regression models of cVEMP amplitude and gait speed
TABLE 1. Gait Usual Rapid Narrow
Model
Aage
P Value
1 2 1 2 1 2
j0.00882 j0.00679 j0.01487 j0.01114 j0.00890 j0.00542
G0.0001 0.0002 G0.0001 0.0003 G0.0001 0.0262
Ac_amp
P Value
0.02127
0.4190
0.06855
0.1230
0.09608
0.0078
cVEMP indicates cervical vestibular-evoked myogenic potential; Model 1, age only; Model 2, age and cVEMP amplitude or latency; Aage, the change in gait speed associated with each 1-year increase in age; Ac_amp, the change in gait speed associated with each 1-unit increase in cVEMP amplitude. Otology & Neurotology, Vol. 36, No. 2, 2015
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A. J. LAYMAN ET AL. Regression models of cVEMP latency and gait speed by gender
TABLE 2. Gait
Model
Aage
P Value
1 2 1 2 1 2
j0.00541 j0.00508 j0.01488 j0.01429 j0.00888 j0.00823
0.0295 0.0333 0.0002 0.0001 0.0103 0.0127
1 2 1 2 1 2
j0.00874 j0.00906 j0.01690 j0.01823 j0.00802 j0.00816
0.0038 0.0030 0.0017 0.0005 0.0576 0.0578
Women Usual
Ac_lat
P Value
Narrow Men Usual Rapid Narrow
j0.0525
0.0197
Rapid
j0.0934
0.0061
Narrow
j0.0798
0.0137
0.03045
0.3201
0.12693
0.0158
0.01242
0.7790
cVEMP indicates cervical vestibular-evoked myogenic potential; Model 1, age only; Model 2, age and cVEMP amplitude or latency; Aage, the change in gait speed associated with each 1-year increase in age; Ac_lat, the change in gait speed associated with each 1-millisecond increase in cVEMP latency.
Neither oVEMP amplitude nor latency appeared to be a mediator of the association between age and gait speed, or had significant independent associations with gait speed in age-adjusted analyses (Tables 3 and 4). DISCUSSION This study evaluated the association between otolith function and age-associated slowing of gait speed. Although previous studies have collected VEMP data in aging populations (22), these data have not been linked to gait performance. Studies that have evaluated the relationship between vestibular function and gait have largely focused on tests of semicircular canal function such as head-impulse testing (24) or head-shake tests (8). Our analysis suggests that impaired saccular function may impact gait speed. Specifically, we found that saccular response magnitude partially mediates the association between age and gait speed, and saccular response timing independently predicts gait speed, and the direction of this latter association differs by sex. The saccular response has two dimensions: magnitude and timing. The magnitude or strength of the response, Regression models of oVEMP amplitude and gait speed
TABLE 3. Gait
Rapid Narrow
Gait Usual
Rapid
Usual
TABLE 4.
Model
Aage
P Value
1 2 1 2 1 2
j0.0101 j0.0098 j0.0166 j0.0156 j0.0093 j0.0098
G0.0001 G0.0001 G0.0001 G0.0001 G0.0001 0.0019
Ao_amp
P Value
j0.0016
0.411
j0.002
0.4957
j0.0015
0.5532
oVEMP indicates ocular vestibular-evoked myogenic potential; Model 1, age only; Model 2, age and oVEMP amplitude or latency; Aage, the change in gait speed associated with each 1-year increase in age; Ao_amp, the change in gait speed associated with each 1-KV increase in oVEMP amplitude.
Regression models of oVEMP latency and gait speed
Model
Aage
P Value
1 2 1 2 1 2
j0.0093 j0.0091 j0.015 j0.0146 j0.0082 j0.0082
G0.0001 G0.0001 G0.0001 G0.0001 G0.0001 G0.0001
Ao_lat
P Value
j0.0124
0.6318
j0.0277
0.493
0.00488
0.8399
oVEMP indicates ocular vestibular-evoked myogenic potential; Model 1, age only; Model 2, age and oVEMP amplitude or latency; Aage, the change in gait speed associated with each 1-year increase in age; Ao_lat, the change in gait speed associated with each 1-millisecond increase in oVEMP latency.
measured by cVEMP amplitude, has been consistently shown to decrease with age (17,19,28). We observed that the association between age and declining gait speed was partially mediated by the decline in cVEMP amplitude with age. Prior studies suggest an important role for the saccule during locomotion (4,5). Vertical linear accelerations in the sagittal plane during locomotion generate shearing forces within the vertically oriented saccular macula, resulting in increased saccular signaling. Saccular signaling may then contribute to head stabilization and postural stabilization during gait via sacculo-collic and sacculospinal reflexes. As such, reduced saccular sensitivity may lead to destabilization and compensatory slowing of gait. Interestingly, direction of association between saccular latency and gait speed appear to differ between men and women. In the presence of increased saccular latency, men have faster gait speeds, whereas women have lower gait speeds. Studies suggest that the adoption of a rapid gait confers greater stability in patients with a vestibulopathy because automated spinal locomotion overrides the vestibular inputs (27,28). However, the advantages associated with a more rapid gait may not be the same for men and women because of differences in hip geometry, body composition (e.g., muscle mass), or center of mass. The different strategies in men and women may alternatively be attributable to a difference in the sensitivity of the saccule to vertical linear displacement between men and women. Although absolute vertical head displacement is larger in men, when corrected for leg length, men and women experience the same relative head bob during gait (29). If the size of the saccule is conserved between men and women, the smaller absolute displacement experienced by women may lead to decreased saccular signaling compared with men. The adoption of gender-specific gait strategies in response to a physiologic impairment has been observed previously. For example, studies have shown that men and women adopt different gait strategies in response to osteoarthritis, with faster and longer leg swings and decreased single-support time being observed in men (30). We present a conceptual causal model of the association between the two dimensions of saccular function (magnitude and timing) and aging and gait speed (Fig. 4). The magnitude of the saccular response appears to partially mediate the association between age and gait speed,
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SACCULAR FUNCTION AND GAIT SPEED
FIG. 4.
265
Conceptual model for association among age, saccular responses magnitude, saccular response timing, and gait speed.
whereas the timing of the saccular response has an independent influence on gait speed. Of note, we did not observe any association between utricular function and gait speed, as evidenced by non-significant oVEMP correlations with gait speed in these data. This may reflect the anatomy and physiology of the utricle. The utricular maculi are horizontally oriented, and are most responsive to head tilt and horizontal translation. Thus utricular dysfunction may not affect gait as markedly as a dysfunction of the saccule. Several limitations of this study should be noted. The participants of this study represent a generally healthy population who are available to travel and are committed to recurrent visits for several decades. Thus, our findings may not be applicable to the general population and in particular to people affected by substantial morbidity. Moreover, we only considered gait speed in this study, and speed is only one performance dimension of gait. Ongoing analyses are currently examining kinematic data from a three-dimensional motion capture system to more fully characterize gait characteristics (e.g., joint movements, center of mass sway) of individuals with decreased otolith and semicircular canal function. However, such measurements may not be readily available to the clinician, making them less practical as a diagnostic or evaluative measure. Finally, our analyses adjusted for age, as a surrogate for age-related losses of other sensory and motor functions that influence gait function. There is a possibility of residual confounding by sensory or motor impairment not captured by the age variable alone. This study confirms age-associated declines in both otolith function and gait speed. These findings further suggest that age-related declines in saccular response magnitude partially mediate the association between age and gait speed in a cohort of community-dwelling individuals. Additionally, these data suggest saccular response latency is an independent predictor of gait speed, and that men and women with increased saccular response latency make opposite adjustments to their gait: men increase gait speed while women decrease gait speed. REFERENCES 1. Horak FB, Shupert CL, Dietz V, et al. Vestibular and somatosensory contributions to responses to head and body displacements in stance. Exp Brain Res 1994;100:93Y106. 2. Goldberg JM. The Vestibular System: A Sixth Sense. Oxford, NY: Oxford University Press, 2012:xiii, 541 p.
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