ORIGINAL COMMUNICATION Cognitive impairment and memory disorders in relapsing–remitting multiple sclerosis: the role of white matter, gray matter and hippocampus R. Sacco 1,2 • A. Bisecco 1 • D. Corbo 2 • M. Della Corte 1,2 • A. d’Ambrosio 1 • R. Docimo 1 • A. Gallo 1,2 • F. Esposito 3 • S. Esposito 1 • M. Cirillo 2,4 • L. Lavorgna 1 • G. Tedeschi 1,2 • S. Bonavita 1,2 Received: 11 December 2014 / Revised: 20 April 2015 / Accepted: 21 April 2015 / Published online: 10 May 2015 Ó Springer-Verlag Berlin Heidelberg 2015 Abstract Cognitive disorders occur in up to 65 % of multiple sclerosis (MS) patients; they have been correlated with different MRI measures of brain tissue damage, whole and regional brain atrophy. The hippocampal involvement has been poorly investigated in cognitively impaired (CI) MS patients. The objective of this study is to analyze and compare brain tissue abnormalities, including hippocampal atrophy, in relapsing–remitting MS (RRMS) patients with and without cognitive deficits, and to investigate their role in determining cognitive impairment in MS. Forty-six RRMS patients [20 CI and 26 cognitively preserved (CP)] and 25 age, sex and education-matched healthy controls (HCs) underwent neuropsychological evaluation and 3-Tesla anatomical MRI. T2 lesion load (T2-LL) was computed with a semiautomatic method, gray matter vol- ume and white matter volume were estimated using SIE- NAX. Hippocampal volume (HV) was obtained by manual segmentation. Brain tissues volumes were compared among groups and correlated with cognitive performances. Compared to HCs, RRMS patients had significant atrophy of WM, GM, left and right Hippocampus (p \ 0.001). Compared to CP, CI RRMS patients showed higher T2-LL (p = 0.02) and WM atrophy (p = 0.01). In the whole RRMS group, several cognitive tests correlated with brain tissue abnormalities (T2-LL, WM and GM atrophy); only verbal memory performances correlated with left hip- pocampal atrophy. Our results emphasize the role of T2-LL and WM atrophy in determining clinically evident cogni- tive impairment in MS patients and provide evidence that GM and hippocampal atrophy occur in MS patients re- gardless of cognitive status. Keywords Multiple sclerosis Á Cognitive disorders Á Hippocampal volumes Á MRI, lesion load, white matter, gray matter Introduction Cognitive disorders (CD) are frequently reported in Mul- tiple Sclerosis (MS) occurring in 40–65 % of patients [1]. They start early in the disease, generally worsen over time and are partially independent of physical disability [1]. The most frequent deficits are found in processing speed, working memory, new learning, visual and verbal memory [2]. Cognitive impairment deeply impacts on quality of life and therapy adherence in MS patients; the definition of its pathogenic mechanisms and the identification of markers useful to monitor its evolution might contribute to identify pharmacologic and rehabilitative strategies. CD have been associated with different magnetic reso- nance imaging (MRI) measures of brain tissue damage such as T2 lesion load (T2-LL) [3], whole brain [4], ven- tricular and cortical volumes [5], corpus callosum size [6] and cortical lesions [7]. The clinical relevance of regional cortical volume, including hippocampal volume, has R. Sacco and A. Bisecco contributed equally to this study. & S. Bonavita simona.bonavita@unina2.it 1 Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy 2 Neurological Institute for Diagnosis and Care ‘‘Hermitage Capodimonte’’, MRI Center SUN-FISM, Naples, Italy 3 Department of Medicine and Surgery, University of Salerno, Baronissi, Salerno, Italy 4 Neuroradiology Service, Department of Radiology, Second University of Naples, Naples, Italy 123 J Neurol (2015) 262:1691–1697 DOI 10.1007/s00415-015-7763-y