Associations of Neurological Biomarkers in Serum With Gait Measures: The Cardiovascular Health Study

Gait impairment leads to increased mobility decline and may have neurological contributions. This study explores how neurological biomarkers are related to gait in older adults.

We studied participants in the Cardiovascular Health Study, a population-based cohort of older Americans, who underwent a serum biomarker assessment from samples collected in 1996-1997 for neurofilament light chain (NfL), glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1, and total tau (n = 1 959, mean age = 78.0 years, 60.8% female). In a subsample (n = 380), cross-sectional associations with quantitative gait measures were explored. This subsample was assessed on a mat for gait speed, step length, double support time, step time, step length variability, and step time variability. Gait speed was also measured over a 15-ft walkway annually from 1996-1997 to 1998-1999 for longitudinal analyses. Linear regression models assessed cross-sectional associations of biomarkers with gait measures, whereas mixed effects models assessed longitudinal gait speed change from baseline to 1998-1999.

Neurofilament light chain was significantly associated with annual gait speed decline (standardized β = -0.64 m/s, 95% CI: [-1.23, -0.06]) after adjustment for demographic and health factors. Among gait mat-assessed phenotypes, NfL was also cross-sectionally associated with gait speed (β = 0.001 m/s [0.0003, 0.002]) but not with other gait measures. None of the remaining biomarkers were significantly related to gait in either longitudinal or cross-sectional analyses.

Higher NfL levels were related to greater annual gait speed decline. Gait speed decline may be related to axonal degeneration. The clinical utility of NfL should be explored.