Associations of Brain Injury Biomarkers in Serum with Gait Measures: The Cardiovascular Health Study

Gait impairment leads to adverse health consequences and has neurological contributions. However, little is known of how specific brain injury biomarkers are associated with multiple quantitative gait measures. Therefore, this study explored how plasma biomarkers of brain injury are related to gait measures in older adults. We hypothesized that higher levels of neurofilament light-chain (NfL) and glial fibrillary acidic protein (GFAP), but lower levels of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and total tau, predict worse gait performance. Participants (n=1959, mean age=78.0 years) were selected from a population-based cohort study and followed from 1998 to 2000. They received a serum biomarker assessment (Quanterix™) at year 9 for NfL, GFAP, UCH-L1, and total tau. Gait speed was measured each year over a 15-ft walkway. Linear mixed effects models assessed the longitudinal association of serum biomarkers with gait speed at year 9 and the annual change, adjusting for demographic factors. A subsample (n=380, mean age=77.6 years) was assessed on a gait mat at year 9 for gait speed, step length, double support time, step time, step length variability and step time variability. Spearman’s correlations and linear regression adjusted for demographic factors assessed the cross-sectional relationship between serum biomarkers and gait mat measures. NfL was significantly associated with baseline gait speed (standardized β= -0.93 m/s [95% CI: -1.62, -0.24]) and the annual change in gait speed (standardized β = -0.69 m/s [-1.28, -0.10]) after adjustment. Results were similar in the gait mat subsample where NfL was significantly associated with gait speed cross-sectionally. No other biomarkers were significantly related to gait measures in longitudinal or cross-sectional analyses. Higher NfL levels were related to slower baseline gait speed and a greater annual decline over 2 years. Gait speed decline may be related to specific aspects of axonal degeneration. Our study can further inform public health efforts to screen those vulnerable to gait impairment