Mobility-related brain regions linking carotid intima-media thickness to specific gait performances in old age

Abstract

Background: Gait disturbance is common in older adults with vascular diseases. However, how carotid atherosclerosis affects gait remains poorly understood. The objectives were to investigate the associations between carotid intima-media thickness and specific gait performances and explore the potential role of brain structure in mediating these associations.

Methods: A cross-sectional analysis of data from the Taizhou Imaging Study was conducted, including 707 individuals who underwent both gait and carotid ultrasound examinations. Gait assessments include the Timed-Up-and-Go test, the Tinetti test, and quantitative gait assessment using a wearable device. Quantitative parameters were summarized into independent gait domains with factor analysis. Magnetic resonance images were obtained on a 3.0-Tesla scanner, and the volumes of fifteen brain regions related to motor function (primary motor, sensorimotor), visuospatial attention (inferior posterior parietal lobules, superior posterior parietal lobules), executive control function (dorsolateral prefrontal cortex, anterior cingulate), memory (hippocampus, entorhinal cortex), motor imagery (precuneus, parahippocampus, posterior cingulated cortex), and balance (basal ganglia: pallidum, putamen, caudate, thalamus) were computed using FreeSurfer and the Desikan-Killiany atlas. Mediation analysis was conducted with carotid intima-media thickness as the predictor and mobility-related brain regions as mediators.

Results: Carotid intima-media thickness was found to be associated with the Timed-Up-and-Go performance (β = 0.129, p = 0.010) as well as gait performances related to pace (β=-0.213, p < 0.001) and symmetry (β = 0.096, p = 0.045). Besides, gait performances were correlated with mobility-related brain regions responsible for motor, visuospatial attention, executive control, memory, and balance (all FDR < 0.05). Notably, significant regions differed depending on the gait outcomes measured. The primary motor (41.9%), sensorimotor (29.3%), visuospatial attention (inferior posterior parietal lobules, superior posterior parietal lobules) (13.8%), entorhinal cortex (36.4%), and motor imagery (precuneus, parahippocampus, posterior cingulated cortex) (27.3%) mediated the association between increased carotid intima-media thickness and poorer Timed-Up-and-Go performance. For the pace domain, the primary motor (37.5%), sensorimotor (25.8%), visuospatial attention (12.3%), entorhinal cortex (20.7%), motor imagery (24.9%), and balance (basal ganglia: pallidum, putamen, caudate, thalamus) (11.6%) acted as mediators.

Conclusions: Carotid intima-media thickness is associated with gait performances, and mobility-related brain volume mediates these associations. Moreover, the distribution of brain regions regulating mobility varies in the different gait domains. Our study adds value in exploring the underlying mechanisms of gait disturbance in the aging population.

Keywords: Brain structure; Carotid intima-media thickness; Gait; Mediation analysis.

Fig. 1

Associations of IMT and IMT-related gait performances with mobility-related brain regions. (Standardized regression coefficients (β) and significance from linear regression models are presented. All models were adjusted for sex, age, standardized total intracranial volume, BMI, hypertension, diabetes, hyperlipidemia, smoking, alcohol consumption, and physical activity. The significance threshold was set at *p < 0.05, **p < 0.01, and ***p < 0.001 after correcting for the false discovery rate.)

Fig. 2

Mediation effects of mobility-related brain regions in the associations between IMT and specific gait performances. (All models were adjusted for sex, age, BMI, hypertension, diabetes, hyperlipidemia, smoking, alcohol consumption, and physical activity. Standardized total intracranial volume was added when brain volume was included. CI, confidence interval.)