NEUROLOGY 2010;74:321-328
© 2010 American Academy of Neurology
Widespread cortical thinning characterizes patients with MS with mild cognitive impairment
M. Calabrese, MD,
F. Rinaldi, MD,
I. Mattisi, MD,
P. Grossi, PhD,
A. Favaretto, MD,
M. Atzori, MD,
V. Bernardi, MD,
L. Barachino, RT,
C. Romualdi, PhD,
L. Rinaldi, MD, PhD,
P. Perini, MD and
P. Gallo, MD, PhD
From The Multiple Sclerosis Centre of Veneto Region–First Neurology Clinic (M.C., F.R., I.M., P.G., A.F., M.A., V.B., L.B., L.R., P.P., P.G.), Department of Neurosciences, University Hospital of Padua; and CRIBI–Biotechnology Centre and Department of Biology (C.R.), University of Padua, Italy.
Address correspondence and reprint requests to Dr. Massimiliano Calabrese, Multiple Sclerosis Centre of Veneto Region, First Neurology Clinic, Department of Neurosciences, University Hospital of Padova, Via Giustiniani 5, 35128 Padova, Italy calabresem{at}hotmail.it
Background: Although cognitive dysfunction affects a relevant portion of patients with multiple sclerosis (MS), its pathologic substrate has not been clarified and it does not seem entirely explained by white matter changes.
Methods: A total of 100 consecutive patients with relapsing remitting MS (RRMS) and 42 normal controls (NC) were enrolled in the study. Cognitive performance was assessed by Rao's Brief Repeatable Battery of Neuropsychological Tests (BRB). Regional cortical thickness (CTh) was evaluated by Freesurfer.
Results: Thirty-one patients with RRMS failed 1 or 2 tests of BRB and were considered to have a mild cognitive impairment (mCI-RRMS), while 8 patients failed at least 3 tests and were classified as markedly impaired (sCI-RRMS). The mean CTh of mCI-RRMS and sCI-RRMS group was significantly lower than in NC (p < 0.001) and cognitively normal patients with RRMS (CN-RRMS) (p < 0.001). The regional analysis revealed significant cortical thinning in frontal and temporal regions (frontotemporal thinning) of CN-RRMS compared to NC, while a widespread pattern of cortical thinning was observed in mCI-RRMS and in sCI-RRMS compared to both CN-RRMS and NC. A correlation was observed between cognitive score (CS) and the mean CTh (r = –0.69, p < 0.001) and between CS and CTh of almost all the cortical areas analyzed (r value between –0.20 and –0.65, p < 0.01). A correlation was found between T2-WM-LV and mean CTh (r = –0.31, p = 0.004) or CS (r = 0.21, p = 0.031). The multivariate analysis confirmed a widespread cortical thinning as the best predictor of cognitive impairment.
Conclusions: A widespread pattern of cortical thinning characterizes patients with cognitive dysfunction, suggesting such dysfunction as expression of a more aggressive and widespread cortical pathology.
Abbreviations: ANOVA = analysis of variance; BDIFS = Beck Depression Inventory–Fast Screen; BRB = Rao's Brief Repeatable Battery of Neuropsychological Tests; CN = cognitively normal; CS = cognitive score; CTh = cortical thickness; DWI = diffusion-weighted imaging; EDSS = Expanded Disability Status Scale; ETL = echo train length; FOV = field of view; GMF = gray matter fraction; mCI = mild cognitive impairment; MR = magnetic resonance; MS = multiple sclerosis; NC = normal controls; PASAT = Paced Auditory Serial Addition Test; RRMS = relapsing remitting multiple sclerosis; sCI = severe cognitive impairment; SDMT = Symbol Digit Modalities Test; SPART = Spatial Recall Test; SRT = Selective Reminding Test; TE = echo time; TI = inversion time; TR = repetition time; WLG = Word List Generation; WM = white matter.
Supplemental data at www.neurology.org
*These authors contributed equally.
Disclosure: The authors report no disclosures.
Received January 28, 2009. Accepted in final form November 4, 2009.
