Differential Associations of Mobility With Fronto-Striatal Integrity and Lesion Load in Older Adults With and Without Multiple Sclerosis

Abstract

Background Mobility impairment is common in older persons with multiple sclerosis (MS), and further compounded by general age-related mobility decline but its underlying brain substrates are poorly understood. Objective Examine fronto-striatal white matter (WM) integrity and lesion load as imaging correlates of mobility outcomes in older persons with and without MS. Methods Fifty-one older MS patients (age 64.9 ± 3.7 years, 29 women) and 50 healthy, matched controls (66.2 ± 3.2 years, 24 women), participated in the study, which included physical and cognitive test batteries and 3T MRI imaging session. Primary imaging measures were fractional anisotropy (FA) and WM lesion load. The relationship between mobility impairment, defined using a validated short physical performance battery cutoff score, and neuroimaging measures was assessed with stratified logistic regression models. FA was extracted from six fronto-striatal circuits (left/right): dorsal striatum (dStr)-to-anterior dorsolateral prefrontal cortex (aDLPFC), dStr-to-posterior DLPFC, and ventral striatum (vStr)-to-ventromedial prefrontal cortex (VMPFC). Results Mobility impairment was significantly associated with lower FA in two circuits, left dStr-aDLPFC ( P = .003) and left vStr-VMPFC ( P = .004), in healthy controls but not in MS patients ( P > .20), for fully adjusted regression models. Conversely, in MS patients but not in healthy controls, mobility impairment was significantly associated with greater lesion volume ( P < .02). Conclusions Comparing older persons with and without MS, we provide compelling evidence of a double dissociation between the presence of mobility impairment and two neuroimaging markers of white matter integrity, fronto-striatal fractional anisotropy, and whole brain lesion load.