Brain tissue volumes and relaxation rates in multiple sclerosis: implications for cognitive impairment
Both normal gray matter atrophy and brain tissue relaxation rates, in addition to total lesion volume, have shown significant correlations with cognitive test scores in multiple sclerosis (MS). Aim of the study was to assess the relative contributions of macro- and microstructural changes of both normal and abnormal brain tissues, probed, respectively, by their volumes and relaxation rates, to the cognitive status and physical disability of MS patients.
MRI studies from 241 patients with relapsing–remitting MS were retrospectively analyzed by fully automated multiparametric relaxometric segmentation. Ordinal backward regression analysis was applied to the resulting volumes and relaxation rates of both normal (gray matter, normal-appearing white matter and CSF) and abnormal (T2-weighted lesions) brain tissues, controlling for age, sex and disease duration, to identify the main independent contributors to the cognitive status, as measured by the percentage of failed tests at a cognitive test battery (Rao’s Brief Repeatable Battery and Stroop test, available in 186 patients), and to the physical disability, as assessed by the Expanded Disability Status Scale (EDSS).
The R1 relaxation rate (a putative marker of tissue disruption) of the MS lesions appeared the single most significant contributor to cognitive impairment (p < 0.001). On the contrary, the EDSS appeared mainly affected by the decrease in R2 of the gray matter (p < 0.0001), (possibly influenced by cortical plaques, edema and inflammation).
In RR-MS the tissue damage in white matter lesions appears the single main determinant of the cognitive status of patients, likely through disconnection phenomena, while the physical disability appears related to the involvement of gray matter.
KeywordsAtrophy Multiple sclerosis Quantitative MRI Relapsing/remitting Cognitive impairment Relaxation rates
Funding by the European Union’s Seventh Framework Programme (FP7/2007–2013) under Grant agreement no. HEALTH-F2-2011-278850 (INMiND), and by the CNR Strategic Project “The Aging: Technological and Molecular Innovations Aiming to Improve the Health of Older Citizens” (http://www.progettoinvecchiamento.it) is gratefully acknowledged.
Compliance with ethical standards
All human studies have been approved by the Institutional Review Board of the university “Federico II” and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
All participants gave informed written consent.
Conflicts of interest
R.L. received personal fees for public speaking or consultancy from Merck, Novartis, Biogen, Genzyme, Teva and Almirall. V.B.M. received personal fees for public speaking or consultancy from Bayer, Mylan, Merck, Novartis, Biogen, Genzyme, Teva and Almirall. M.M. declares that he has received honoraria and support for travelling from Almirall, Coloplast, Genzyme and Merck Serono. R.M., B.A., T.C., M.C., G.V., A.C., A.P., G.S., and M.Q. declare that they have no conflict of interest.
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