Thalamic atrophy moderates associations among aerobic fitness, cognitive processing speed, and walking endurance in persons with multiple sclerosis

Background and objectives: Thalamic atrophy (TA) represents a biomarker of neurodegeneration and associated dysfunction/decline in physical and cognitive functioning among persons with multiple sclerosis (MS). Aerobic fitness, as an end point of exercise training, represents a promising target for restoring function in MS, but it is unknown if such effects differ by TA. This cross-sectional study examined whether aerobic fitness was differentially associated with cognitive processing speed and walking endurance in persons with MS who present with and without TA. Methods: 44 fully ambulatory persons with MS completed a graded exercise test for measuring aerobic fitness (VO_2peak) and underwent 3T MRI for measuring TA, the Symbol Digit Modalities Test (SDMT), and the 6-min walk (6MW). We performed Spearman correlations (r_s) among VO_2peak, SDMT, and 6MW scores overall, and in persons with and without TA. We applied Fisher’s z-test for comparing correlations based on TA status. Results: When controlling for age, EDSS score, and global MRI measures of atrophy, VO_2peak was strongly associated with SDMT scores (pr_s = 0.74, p < 0.01) and 6MW performance (pr_s = 0.77, p < 0.01) in persons with TA, whereas VO_2peak was not associated with SDMT scores (pr_s = − 0.01, p = 0.99) or 6MW performance (pr_s = 0.25, p = 0.38) in those without TA. The correlations between VO_2peak and SDMT (z = 2.86, p < 0.01) and VO_2peak and 6MW (z = 2.33, p = 0.02) were significantly stronger in the TA group. Discussion: This study provides initial evidence of strong, selective associations among aerobic fitness, cognitive processing speed, and walking endurance in persons with TA as a biomarker for MS-related neurodegeneration. Such data support TA as a moderator of the association among aerobic fitness, cognitive processing speed, and walking endurance in persons with MS. Future research should carefully consider the role of TA when designing trials of aerobic exercise, cognition, and mobility in MS.