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

BACKGROUND: Cognitive impairment is a disabling and underestimated consequence of multiple sclerosis (MS), with multiple determinants that are poorly understood. OBJECTIVES: We 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. METHODS: We 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. RESULTS: Interhemispheric 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. DISCUSSION: Corticospinal 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.