These data are the first to demonstrate two main findings: 1) There is a significant reduction in OCR linearly related to age that is greater in females then males; and 2) Reductions in otolith function are correlated to sway measures that are known risk factors for falls.
Our finding of a reduction in otolith-ocular function related to age () is consistent with previous data from samples as large as a 1000 patients in which decreases in amplitude of the vestibular evoked myogenic potential (VEMP) were correlated with increasing age, reporting R2
values of 0.21 [2
] and 0.14–0.22, depending on stimulus intensity [20
]. Therefore, the VEMP changes with age are comparable to OCR. These data in combination with our current data suggest that both otolith saccule (VEMP) and utricle (OCR) function decrease with age.
This decreased otolith function is likely due to morphological changes in the otoliths since both the number of hair cells and otoconia mass decrease with age [23
]. Ross et al [26
] demonstrated that the first change in the human vestibular system is demineralization of the otoliths. In addition, decreases in hair cell number have been found to be linearly related to age [17
], consistent with our functional change in OCR. Increasing age is associated with decreased blood flow to the utricle [14
] and attenuation of the neural response to otolith activation.[24
] This is supported by the attenuated otolith-ocular responses of older subjects during linear acceleration stimuli.[8
Our data are the first to demonstrate a sex difference in the age related decline in otolith-ocular function. While our female subjects demonstrated twice the decrease in OCR per decade than our males (~10% per decade for females compared to 5% for males), previous data using VEMP found no sex differences.[2
] The reason for this difference remains unclear. One possibility is sex-dependent aging effects may differ between utricular (OCR) vs saccular (VEMP) function. Another possibility is that variability in the VEMP response may obscure the underlying sex difference. Further work is necessary to clarify this disparity.
The increase in postural sway in older subjects was first shown by Peterka and Black [21
]. Subsequent to this initial publication, Black et al. reported over a three decade longitudinal study that changes in vestibular function decreased equally in each decade for this same population [1
]. Interestingly, subjects in the lower 50th
percentile showed decrements as early as the 2nd
decade in females and the 4th
decade for males.
Our data raise the question of whether loss of otolith function with age may be related to increased fall risk. While direct measures of falls during activities of daily living in these subjects were not performed, correlations to various balance measures that have been assessed with regards to fall risk were performed. We found a strikingly strong relationship between OCR and mediolateral sway with eyes closed on a firm surface (Figure 3). In a review of studies examining the use of force platform measures to predict falls, the best predictors were ML sway amplitude with eyes open and closed and the ML RMS [22
]. Similarly in both an ambulatory and independent older population aged 62–96 years, ML sway with eyes closed was closely correlated with future falling risk and was able to predict falls in individuals with no recent history of falling [15
]. Based on our current data, subjects with increased mediolateral sway also had significantly reduced OCR, suggesting the role of otolith function in falls appears to be an important area for consideration.
In addition in the subjects that were classified as having a fall during the balance trials, their OCR values were significantly lower than non-fallers. In fact, the only two subjects under age 50 that fell had OCR values of 0.03 and 0.09, which were extremely low for their age group. In addition, if we compare ML sway in fallers vs. non-fallers of the same age range, the only condition in which fallers had significantly greater sway was the eyes closed on a firm surface, which is closely correlated to future falling risk [15
]. These data suggest that even in young subjects, low OCR may be related to increased likelihood of falls when missing visual information.
If OCR is related to fall risk, based on our finding of a linear decrease in OCR, one would expect an increase in fall incidence with increasing age. Consistent with this, Era et al [7
] found that sway measures increased in subjects from young to middle age to older subjects. Elderly patients (65–74) with bilateral vestibular loss had a 2.5x greater incidence of falls and unilateral patients had 1.6x greater incidence than aged matched controls [11
]. Talbot et al [29
], found that fall incidence increased from young to middle to older adults and that rates were higher in women than men. These data are consistent with our finding that the rate of decrease in OCR is greater in women.
However, the mechanism for these gender effects remains unclear. Previous data examining hair cell loss with aging found no sex differences [17
]. One possible explanation is that loss of calcium from the otoconia could reduce the response of the otoliths. Consistent with this, women demonstrate significantly greater bone mineral density decreases throughout life than men [34
]. In addition women with benign paroxysmal positional vertigo are more likely to have reduced bone mineral density than age matched controls [33
]. Thus, indirect evidence may suggest a connection between bone loss and vestibular issues, however, further work is needed to determine the mechanism behind the greater OCR decrease in women.
One possible explanation for the correlation between OCR and measures of mediolateral postural sway may be the fact that both are impaired with age. However, if this were true then all measures of postural control function that were significantly correlated with increasing age, should positively correlate with reduced OCR gain. However, we found that anterior-posterior measures of sway were not correlated with OCR, even though they were correlated with age. In addition, we found that this strong relationship between ML sway and OCR was present in the elderly group alone even though there was not a wide spread in age in this group ( lower right panel). Therefore, age alone does not explain this effect. These data suggest an independent role for OCR in the relationship between vestibular and postural control function. However, further longitudinal work using expanded measures of vestibular otolith function, postural sway and falls are necessary to substantiate this finding.
While we found a reduction in OCR with age, this study used a cross sectional design. Thus, we cannot exclude the possibility that subjects with reduced OCR when older did not also have impaired function when younger. However, comparing the OCR of our under 30 and over 60 subjects, the likelihood that these values came from the same population is ~1.5% (T-test, P=0.015). In addition we did not directly measure falls in our subjects so we could not directly correlate OCR with fall risk.
The fact that OCR was significantly correlated with measures of ML sway is not surprising since both occur in the roll plane. It’s important to note that this was the case for a natural stance in which subjects stood with feet spaced shoulder width apart, i.e., their base of support was greater in the ML direction. The effect would have been arguably more evident with a narrower stance such as tandem or standing on one leg. This further underscores the potential of OCR as a fall risk indicator since control of ML sway is important in dynamic movements such as navigating corners, which most vestibular impaired patients find challenging.
To our knowledge these are the first data to demonstrate that there is a linearly related age related decline in utricular otolith-ocular function that is correlated with mediolateral measures of postural sway. In addition our data demonstrate a greater age-related decrement in females than males. Finally, the loss of otolith function is correlated with impairment of postural control measures that are associated with increased risk of falls. This is consistent with our hypothesis that loss of utricular otolith function contributes significantly to fall risk in the elderly.