Magnetic resonance imaging techniques as predictors of cognitive impairment in multiple sclerosis

Objectives. The aim of the present exploratory study, which replicates the principal inclusion criteria of most recent clinical trials in patients with relapsing-remitting form of MS, was to establish which magnetic resonance imaging (MRI) parameter is the best predictor of cognitive impairment. This issue could have important implications in choosing MRI protocols for clinical trials in MS, when cognitive dysfunction is considered a secondary clinical outcome. Material and methods. We studied 63 patients with clinically definite relapsing-remitting MS, disease duration 1-10 years and Expanded Disability Status Scale (EDSS) ≤ 5.0. The neuropsychological performances, the psychological functioning, the neurologic impairment and disability have been assessed. Patients also underwent PD/T2- and T1- weighted, and magnetization transfer (MT) brain MRI. Post imaging analysis comprised quantification of total and regional lesion loads, brain atrophy (BA) scores and measures, and normal appearing white matter (NAWM) magnetization transfer ratio (MTR). The relationship between cognitive impairment and MRI abnormalities was investigated by partial correlation and stepwise multiple regression analysis excluding the effects of age, education, depression and anxiety. Results. We did not find any correlation between total and regional lesion loads, BA scores and measures, and overall cognitive impairment, although substantial part of our sample of patients had cognitive deficits (23 patients, 38.1%). Overall cognitive impairment correlated only with NAWM MTR total (r= -0.38, p=0.003) and with NAWM MTR frontal (r= -0.46, p= <0.0001). Multiple regression analysis revealed that total and regional BA scores and NAWM MTR predicted best the neuropsychological variables exploring the frontal lobe function. Conclusions. Our data suggest that in relapsing-remitting MS patients, with low disability score and short disease duration, the overall cognitive impairment probably relies more on microscopic changes in NAWM and parenchimal atrophy than on extent of disease burden in the brain. When cognitive impairment is considered a secondary clinical outcome in MS trials, MT and BA should be considered in the MRI protocol.