Age and asymmetry of corticospinal excitability, but not cardiorespiratory fitness, predict cognitive impairments in multiple sclerosis

Abstract

BackgroundCognitive impairment is a disabling and underestimated consequence of multiple sclerosis (MS), with multiple determinants that are poorly understood. ObjectivesWe explored predictors of MS-related processing speed impairment (PSI) and age-related mild cognitive impairment (MCI) and hypothesized that cardiorespiratory fitness and corticospinal excitability would predict these impairments. MethodsWe screened 73 adults with MS (53 females; median [range]: Age 48 [21–70] years, EDSS 2.0 [0.0–6.5]) for PSI and MCI using the Symbol Digit Modalities Test and Montréal Cognitive Assessment, respectively. We identified six persons with PSI (No PSI, n = 67) and 13 with MCI (No MCI, n = 60). We obtained clinical data from medical records and self-reports; used transcranial magnetic stimulation to test corticospinal excitability; and assessed cardiorespiratory fitness using a graded maximal exercise test. We used receiver operator characteristic (ROC) curves to discern predictors of PSI and MCI. ResultsInterhemispheric asymmetry of corticospinal excitability was specific for PSI, while age was both sensitive and specific for MCI. MS-related PSI was also associated with statin prescriptions, while age-related MCI was related to progressive MS and GABA agonist prescriptions. Cardiorespiratory fitness was associated with neither PSI nor MCI. DiscussionCorticospinal excitability is a potential marker of neurodegeneration in MS-related PSI, independent of age-related effects on global cognitive function. Age is a key predictor of mild global cognitive impairment. Cardiorespiratory fitness did not predict cognitive impairments in this clinic-based sample of persons with MS.