Slowing of gait speed and falls in older people are often due to complex and multifactorial pathophysiologies. The primary goal of our study was to better understand their association with cerebrovascular hemodynamics by examining the relationship between cerebral blood flow regulation, slow gait speed, and the development of falls. Data from population-based studies linking cerebrovascular hemodynamics to slowing of gait speed and the development of falls have not been previously published.
Our data indicate that cerebral vasoreactivity to CO2
, a measure of cerebral endothelial function,8–11
is associated with slower gait speed and marginally with falls. It appears that those in the lowest quintile of VR may have a higher rate of falls compared to those in the highest quintile of VR. Given that low cerebral VR is also associated with WMSA,6,7
the relationship between impairments in VR and mobility may be mediated by WMSA. However, in the absence of imaging data, this possibility is speculative.
Unlike cerebral VR, measures of pressure regulation (cerebral autoregulation) were not related to falls or slow gait speed. Given that age-related WMSA accumulate in the deep watershed border zones, it was our expectation that impaired pressure autoregulation would be associated with slow gait speed and predictive of falls. Our group,26
as well as others,34–36
have previously demonstrated that in a number of other clinical entities, including aging, hypertension, stroke, and carotid stenosis, there is a dissociation between cerebral VR and measures of cerebral pressure autoregulation. In other words, these clinical conditions are all associated with intact cerebral autoregulation, but impaired cerebral VR. One explanation for this dissociation may be that our current measures of autoregulation are not sensitive enough to detect subtle changes. It is also possible that impaired autoregulation occurs after the development of endothelial dysfunction, and with time this association may emerge. The presence and magnitude of WMSA could help us to understand better the dissociation between cerebral vasoreactivity and autoregulation, but our cohort did not have MRI.
Based on recent data which show that individuals with weaker quadriceps muscle strength had greater gait variability and an enhanced effect of WMSA volume on falls,5
we also examined the relationship between cerebral VR and motor function, as measured by SPPB and leg muscle strength. We did not find any association between cerebral VR and these measures of motor function. Our findings suggest that with the exception of gait speed, these other measures of motor function do not appear to be related to cerebral VR. Interestingly, while those individuals in the lowest quintiles of vasoreactivity had lower gait speed and higher fall rates compared to those in the highest quintile, the results were not as clear in middle quintiles, especially in quintile 2. One possible explanation for these findings may be the nonlinear relationship between these variables.
Our study provides novel evidence that impaired cerebral vasoreactivity, as a measure of endothelial function, is associated with slow gait speed and the development of falls in elderly people without dementia. Given that a number of measures such as statins, angiotensin converting enzyme inhibitors (ACEI), and daily exercise can improve endothelial function, as well as promote endothelial repair mechanisms,37
our findings suggest a novel strategy for the prevention of falls in elderly people. The potential value of cardiovascular risk reduction for the prevention of falls is underscored by recent findings that blood pressure lowering with ACEI leads to regression of WMSA.38
There are several limitations to our study. First, the absence of imaging data limits our ability to draw conclusions about the role of WMSA or other structural lesions in our findings. Despite ample data linking WMSA to gait disorders and falls, and WMSA to impaired cerebral VR, there are no direct data on the relationship among all 3 factors. Future imaging studies in our cohort will provide the necessary data to directly examine these relationships. Second, the individuals in the cohort who had a TCD window were generally healthier than those who did not have a window, limiting the generalizability of our findings. While a TCD window is absent in about 35% of the elderly population, no prior studies have compared the clinical characteristics of those with and without a TCD window. Overall, it seems that those who had a window were more likely to be healthy white males. Traditionally, hyperostosis of the skull has been identified as the main obstacle to transtemporal insonation of the basal cerebral arteries. How the differences between those with and without a TCD window relate to hyperostosis or whether there are entirely different mechanisms at play that result in failure of transtemporal insonation is unknown. Third, it is important to note that a number of prior studies have established that the traditional measure of cerebral VR (MFV changes in response to changes in end-tidal CO2) is a complex measure which may also reflect the effects of simultaneous changes in MAP. Fourth, we must also emphasize that this is a cross-sectional study of VR and gait speed. With the future availability of longitudinal data and MRIs from our cohort, we may find that WMSA are the cause of both impaired VR and slow gait. Until we have these data, the causal pathway remains unknown. Finally, it is important to note that while our discussion has been limited to endothelial function and NO reactivity, there may be a host of other factors that could be responsible for the change in VR.
Despite these limitations, our findings are novel and advance our understanding of the relationship between cerebral vasoreactivity, slow gait, and falls. They also should motivate future studies to better define the role of WMSA in the relationship between impaired cerebral VR and falls. These studies will have significant therapeutic implications. Identification of early markers of cerebrovascular dysfunction that are predictive of falls will be an important step toward prevention of these devastating events in elderly people.