Skip to main content
Erschienen in: Journal of Neurology 7/2015

01.07.2015 | Original Communication

Cognitive impairment and memory disorders in relapsing–remitting multiple sclerosis: the role of white matter, gray matter and hippocampus

verfasst von: R. Sacco, A. Bisecco, D. Corbo, M. Della Corte, A. d’Ambrosio, R. Docimo, A. Gallo, F. Esposito, S. Esposito, M. Cirillo, L. Lavorgna, G. Tedeschi, S. Bonavita

Erschienen in: Journal of Neurology | Ausgabe 7/2015

Einloggen, um Zugang zu erhalten

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 volume and white matter volume were estimated using SIENAX. 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 hippocampal atrophy. Our results emphasize the role of T2-LL and WM atrophy in determining clinically evident cognitive impairment in MS patients and provide evidence that GM and hippocampal atrophy occur in MS patients regardless of cognitive status.
Literatur
1.
2.
Zurück zum Zitat Chiaravalloti ND, DeLuca J (2008) Cognitive impairment in multiple sclerosis. Lancet Neurol 7:1139–1151CrossRefPubMed Chiaravalloti ND, DeLuca J (2008) Cognitive impairment in multiple sclerosis. Lancet Neurol 7:1139–1151CrossRefPubMed
3.
Zurück zum Zitat Benedict RH, Weinstock-Guttman B, Fishman I et al (2004) Prediction of neuropsychological impairment in multiple sclerosis: comparison of conventional magnetic resonance imaging measures of atrophy and lesion burden. Arch Neurol 61:226–230CrossRefPubMed Benedict RH, Weinstock-Guttman B, Fishman I et al (2004) Prediction of neuropsychological impairment in multiple sclerosis: comparison of conventional magnetic resonance imaging measures of atrophy and lesion burden. Arch Neurol 61:226–230CrossRefPubMed
4.
Zurück zum Zitat Zivadinov R, Sepcic J, Nasuelli D et al (2001) A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychol 70:773–780CrossRef Zivadinov R, Sepcic J, Nasuelli D et al (2001) A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychol 70:773–780CrossRef
5.
Zurück zum Zitat Benedict RH, Bruce JM, Dwyer MG et al (2006) Neocortical atrophy, third ventricular width, and cognitive dysfunction in multiple sclerosis. Arch Neurol 63:1301–1306CrossRefPubMed Benedict RH, Bruce JM, Dwyer MG et al (2006) Neocortical atrophy, third ventricular width, and cognitive dysfunction in multiple sclerosis. Arch Neurol 63:1301–1306CrossRefPubMed
6.
Zurück zum Zitat Pelletier J, Suchet L, Witjas T et al (2001) A longitudinal study of callosal atrophy and interhemispheric dysfunction in relapse-remitting multiple sclerosis. Arch Neurol 58:105–111CrossRefPubMed Pelletier J, Suchet L, Witjas T et al (2001) A longitudinal study of callosal atrophy and interhemispheric dysfunction in relapse-remitting multiple sclerosis. Arch Neurol 58:105–111CrossRefPubMed
7.
Zurück zum Zitat Roosendaal SD, Moraal B, Pouwels PJ et al (2009) Accumulation of cortical lesions in MS: relation with cognitive impairment. Mult Scler 15(6):708–714CrossRefPubMed Roosendaal SD, Moraal B, Pouwels PJ et al (2009) Accumulation of cortical lesions in MS: relation with cognitive impairment. Mult Scler 15(6):708–714CrossRefPubMed
8.
Zurück zum Zitat Sicotte NL, Kern KC, Giesser BS et al (2008) Regional hippocampal atrophy in multiple sclerosis. Brain 131(pt 4):1134–1141CrossRefPubMed Sicotte NL, Kern KC, Giesser BS et al (2008) Regional hippocampal atrophy in multiple sclerosis. Brain 131(pt 4):1134–1141CrossRefPubMed
9.
Zurück zum Zitat Kiy G, Lehmann P, Hahn HK et al (2011) Decreased hippocampal volume, indirectly measured, is associated with depressive symptoms and consolidation deficits in multiple sclerosis. Mult Scler 17(9):1088–1097CrossRefPubMed Kiy G, Lehmann P, Hahn HK et al (2011) Decreased hippocampal volume, indirectly measured, is associated with depressive symptoms and consolidation deficits in multiple sclerosis. Mult Scler 17(9):1088–1097CrossRefPubMed
10.
Zurück zum Zitat Anderson VM, Fisniku LK, Zi Khaleel et al (2010) Hippocampal atrophy in relapsing-remitting and primary progressive MS: a comparative study. Mult Scler 16(9):1083–1090CrossRefPubMed Anderson VM, Fisniku LK, Zi Khaleel et al (2010) Hippocampal atrophy in relapsing-remitting and primary progressive MS: a comparative study. Mult Scler 16(9):1083–1090CrossRefPubMed
12.
Zurück zum Zitat Bird CM, Burgess N (2008) The hippocampus and memory: insights from spatial processing. Nat Rev Neurosci 9:182–194CrossRefPubMed Bird CM, Burgess N (2008) The hippocampus and memory: insights from spatial processing. Nat Rev Neurosci 9:182–194CrossRefPubMed
13.
Zurück zum Zitat Geurts JJ, Bö L, Roosendaal SD et al (2007) Extensive hippocampal demyelination in multiple sclerosis. J Neuropathol Exp Neurol 66(9):819–827CrossRefPubMed Geurts JJ, Bö L, Roosendaal SD et al (2007) Extensive hippocampal demyelination in multiple sclerosis. J Neuropathol Exp Neurol 66(9):819–827CrossRefPubMed
14.
Zurück zum Zitat Roosendaal SD, Moraal B, Vrenken H et al (2008) In vivo MR imaging of hippocampal lesions in multiple sclerosis. J Magn Reson Imaging 27(4):726–731CrossRefPubMed Roosendaal SD, Moraal B, Vrenken H et al (2008) In vivo MR imaging of hippocampal lesions in multiple sclerosis. J Magn Reson Imaging 27(4):726–731CrossRefPubMed
15.
Zurück zum Zitat Sumowski JF, Wylie GR, De Luca J, Chiaravalloti N (2010) Intellectual enrichment is linked to cerebral efficiency in multiple sclerosis: functional magnetic resonance imaging evidence for cognitive reserve. Brain 133:362–374PubMedCentralCrossRefPubMed Sumowski JF, Wylie GR, De Luca J, Chiaravalloti N (2010) Intellectual enrichment is linked to cerebral efficiency in multiple sclerosis: functional magnetic resonance imaging evidence for cognitive reserve. Brain 133:362–374PubMedCentralCrossRefPubMed
16.
Zurück zum Zitat Roosendaal SD, Hulst HE, Vrenken H et al (2010) Structural and Functional Hippocampal Changes in Multiple Sclerosis Patients with Intact Memory Function. Radiology 255:595–604CrossRefPubMed Roosendaal SD, Hulst HE, Vrenken H et al (2010) Structural and Functional Hippocampal Changes in Multiple Sclerosis Patients with Intact Memory Function. Radiology 255:595–604CrossRefPubMed
17.
Zurück zum Zitat Hulst HE, Schoonheim MM, Roosendaal SD et al (2012) Functional adaptive changes within the hippocampal memory system of patients with multiple sclerosis. Hum Brain Mapp 33(10):2268–2280CrossRefPubMed Hulst HE, Schoonheim MM, Roosendaal SD et al (2012) Functional adaptive changes within the hippocampal memory system of patients with multiple sclerosis. Hum Brain Mapp 33(10):2268–2280CrossRefPubMed
18.
Zurück zum Zitat Polman CH, Reingold SC, Edan G et al (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 58:840–846CrossRefPubMed Polman CH, Reingold SC, Edan G et al (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 58:840–846CrossRefPubMed
19.
Zurück zum Zitat Spielberg CD, Gorsuch RL, Luskene RE (1996) STAI, State-Trait Anxiety Inventory, Forma Y. Florence, Organizzazioni Speciali Spielberg CD, Gorsuch RL, Luskene RE (1996) STAI, State-Trait Anxiety Inventory, Forma Y. Florence, Organizzazioni Speciali
20.
Zurück zum Zitat Solari A, Motta A, Mendozzi L et al (2004) Italian version of the Chicago multiscale depression inventory: translation, adaptation and testing in people with multiple sclerosis. Neurol Sci 24(6):375–383CrossRefPubMed Solari A, Motta A, Mendozzi L et al (2004) Italian version of the Chicago multiscale depression inventory: translation, adaptation and testing in people with multiple sclerosis. Neurol Sci 24(6):375–383CrossRefPubMed
21.
Zurück zum Zitat Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452CrossRefPubMed Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452CrossRefPubMed
22.
Zurück zum Zitat Rao SM, Leo GJ, Bernardin L et al (1991) Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 41(5):685–691CrossRefPubMed Rao SM, Leo GJ, Bernardin L et al (1991) Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 41(5):685–691CrossRefPubMed
23.
Zurück zum Zitat Amato MP, Portaccio E, Goretti B et al (2006) The Rao’s Brief Repeatable Battery and Stroop Test: normative values with age, education and gender corrections in an Italian population. Mult Scler 12:787–793CrossRefPubMed Amato MP, Portaccio E, Goretti B et al (2006) The Rao’s Brief Repeatable Battery and Stroop Test: normative values with age, education and gender corrections in an Italian population. Mult Scler 12:787–793CrossRefPubMed
24.
Zurück zum Zitat Smith SM, Zhang Y, Jenkinson M et al (2002) Accurate, robust and automated longitudinal and cross-sectional brain change analysis. NeuroImage 17:479–489CrossRefPubMed Smith SM, Zhang Y, Jenkinson M et al (2002) Accurate, robust and automated longitudinal and cross-sectional brain change analysis. NeuroImage 17:479–489CrossRefPubMed
25.
Zurück zum Zitat Zhang Y, Brady M, Smith S (2001) Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans Med Imaging 20:45–57CrossRefPubMed Zhang Y, Brady M, Smith S (2001) Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans Med Imaging 20:45–57CrossRefPubMed
26.
Zurück zum Zitat Battaglini M, Jenkinson M, De Stefano N (2012) Evaluating and reducing the impact of white matter lesions on brain volume measurements. Hum Brain Mapp 33:2062–2071CrossRefPubMed Battaglini M, Jenkinson M, De Stefano N (2012) Evaluating and reducing the impact of white matter lesions on brain volume measurements. Hum Brain Mapp 33:2062–2071CrossRefPubMed
27.
Zurück zum Zitat Pruessner JC, Li LM, Serles W et al (2000) Volumetry of hippocampus and amygdala with high-resolution MRI and three-dimensional analysis software: minimizing the discrepancies between laboratories. Cereb Cortex 10:433–442CrossRefPubMed Pruessner JC, Li LM, Serles W et al (2000) Volumetry of hippocampus and amygdala with high-resolution MRI and three-dimensional analysis software: minimizing the discrepancies between laboratories. Cereb Cortex 10:433–442CrossRefPubMed
28.
Zurück zum Zitat Cavedo E, Redolfi A, Angeloni F et al (2014) The Italian Alzheimer’s disease neuroimaging initiative (I-ADNI): validation of structural MR imaging. J Alzheimer’s Dis 40(4):941–952 Cavedo E, Redolfi A, Angeloni F et al (2014) The Italian Alzheimer’s disease neuroimaging initiative (I-ADNI): validation of structural MR imaging. J Alzheimer’s Dis 40(4):941–952
29.
Zurück zum Zitat Pedraza O, Bowers D, Gilmore R (2004) Asymmetry of the hippocampus and amygdala in MRI volumetric measurements of normal adults. J Int Neuropsychol Soc 10(5):664–678CrossRefPubMed Pedraza O, Bowers D, Gilmore R (2004) Asymmetry of the hippocampus and amygdala in MRI volumetric measurements of normal adults. J Int Neuropsychol Soc 10(5):664–678CrossRefPubMed
30.
Zurück zum Zitat Giorgio A, De Stefano N (2010) Cognition in Multiple Sclerosis: relevance of lesions, Brain atrophy and proton MR spectroscopy. Neurol Sci 31(Suppl 2):S245–S248CrossRefPubMed Giorgio A, De Stefano N (2010) Cognition in Multiple Sclerosis: relevance of lesions, Brain atrophy and proton MR spectroscopy. Neurol Sci 31(Suppl 2):S245–S248CrossRefPubMed
31.
Zurück zum Zitat Rocca MA, Amato MP, De Stefano N et al (2015) Clinical and imaging assessment of cognitive dysfunction in multiple sclerosis. Lancet Neurol 14(3):302–317CrossRefPubMed Rocca MA, Amato MP, De Stefano N et al (2015) Clinical and imaging assessment of cognitive dysfunction in multiple sclerosis. Lancet Neurol 14(3):302–317CrossRefPubMed
32.
Zurück zum Zitat Hou G, Yang X, Yuan TF (2013) Hippocampal asymmetry: differences in structures and functions. Neurochem Res 38(3):453–460CrossRefPubMed Hou G, Yang X, Yuan TF (2013) Hippocampal asymmetry: differences in structures and functions. Neurochem Res 38(3):453–460CrossRefPubMed
33.
Zurück zum Zitat Hulst HE, Steenwijk MD, Versteeg A et al (2013) Cognitive impairment MS: impact of white matter integrity, gray matter volume, and lesions. Neurology 80(11):1025–1032CrossRefPubMed Hulst HE, Steenwijk MD, Versteeg A et al (2013) Cognitive impairment MS: impact of white matter integrity, gray matter volume, and lesions. Neurology 80(11):1025–1032CrossRefPubMed
34.
Zurück zum Zitat Papadopoulou A, Müller-Lenke N, Naegelin Y et al (2013) Contribution of cortical and white matter lesions to cognitive impairment in multiple sclerosis. Mult Scler 19:1290–1296CrossRefPubMed Papadopoulou A, Müller-Lenke N, Naegelin Y et al (2013) Contribution of cortical and white matter lesions to cognitive impairment in multiple sclerosis. Mult Scler 19:1290–1296CrossRefPubMed
35.
Zurück zum Zitat Llufriu S, Martinez-Heras E, Fortea J et al (2014) Cognitive functions in multiple sclerosis: impact of gray matter integrity. Mult Scler 20:424–432CrossRefPubMed Llufriu S, Martinez-Heras E, Fortea J et al (2014) Cognitive functions in multiple sclerosis: impact of gray matter integrity. Mult Scler 20:424–432CrossRefPubMed
36.
Zurück zum Zitat Patti F, De Stefano M, Lavorgna L et al (2015) Lesion load may predict long-term cognitive dysfunction in multiple sclerosis patients. PLoS One 10(3):e0120754PubMedCentralCrossRefPubMed Patti F, De Stefano M, Lavorgna L et al (2015) Lesion load may predict long-term cognitive dysfunction in multiple sclerosis patients. PLoS One 10(3):e0120754PubMedCentralCrossRefPubMed
37.
Zurück zum Zitat Sanfilipo MP, Benedict RHB, Weinstock-Guttman B, Bakshi R (2006) Gray and white matter brain atrophy and neuropsychological impairment in multiple sclerosis. Neurology 66(5):685–692CrossRefPubMed Sanfilipo MP, Benedict RHB, Weinstock-Guttman B, Bakshi R (2006) Gray and white matter brain atrophy and neuropsychological impairment in multiple sclerosis. Neurology 66(5):685–692CrossRefPubMed
38.
Zurück zum Zitat Covey TJ1, Zivadinov R, Shucard JL, Shucard DW (2011) Information processing speed, neural efficiency, and working memory performance in multiple sclerosis: differential relationships with structural magnetic resonance imaging. J Clin Exp Neuropsychol 33(10):1129–1145 Covey TJ1, Zivadinov R, Shucard JL, Shucard DW (2011) Information processing speed, neural efficiency, and working memory performance in multiple sclerosis: differential relationships with structural magnetic resonance imaging. J Clin Exp Neuropsychol 33(10):1129–1145
39.
Zurück zum Zitat Guimara˜es J, Sa´ MJ (2012) Cognitive dysfunction in multiple sclerosis. Front Neurol 3:74 Guimara˜es J, Sa´ MJ (2012) Cognitive dysfunction in multiple sclerosis. Front Neurol 3:74
40.
Zurück zum Zitat Dineen RA, Vilisaar J, Hlinka J et al (2009) Disconnection as a mechanism for cognitive dysfunction in multiple sclerosis. Brain 132:239–249CrossRefPubMed Dineen RA, Vilisaar J, Hlinka J et al (2009) Disconnection as a mechanism for cognitive dysfunction in multiple sclerosis. Brain 132:239–249CrossRefPubMed
41.
Zurück zum Zitat Mesaros S, Rocca MA, Kacar K et al (2012) Diffusion tensor MRI tractography and cognitive impairment in multiple sclerosis. Neurology 78:969–975CrossRefPubMed Mesaros S, Rocca MA, Kacar K et al (2012) Diffusion tensor MRI tractography and cognitive impairment in multiple sclerosis. Neurology 78:969–975CrossRefPubMed
42.
Zurück zum Zitat Bisecco A, Rocca MA, Pagani E et al (2015) Connectivity-based parcellation of the thalamus in multiple sclerosis and its implications for cognitive impairment: A multicenter study. Hum Brain Mapp. doi:10.1002/hbm.22809 PubMed Bisecco A, Rocca MA, Pagani E et al (2015) Connectivity-based parcellation of the thalamus in multiple sclerosis and its implications for cognitive impairment: A multicenter study. Hum Brain Mapp. doi:10.​1002/​hbm.​22809 PubMed
43.
Zurück zum Zitat Bonavita S, Gallo A, Sacco R et al (2011) Distributed changes in default-mode resting-state connectivity in multiple sclerosis. Mult Scler 17:411–422CrossRefPubMed Bonavita S, Gallo A, Sacco R et al (2011) Distributed changes in default-mode resting-state connectivity in multiple sclerosis. Mult Scler 17:411–422CrossRefPubMed
44.
Zurück zum Zitat Rocca MA, Valsasina P, Absinta M et al (2010) Default-mode network dysfunction and cognitive impairment in progressive MS. Neurology 20(74):1252–1259CrossRef Rocca MA, Valsasina P, Absinta M et al (2010) Default-mode network dysfunction and cognitive impairment in progressive MS. Neurology 20(74):1252–1259CrossRef
45.
Zurück zum Zitat Sumowski JF, Wylie GR, Leavitt VM et al (2013) Default network activity is a sensitive and specific biomarker of memory in multiple sclerosis. Mult Scler 19(2):199–208CrossRefPubMed Sumowski JF, Wylie GR, Leavitt VM et al (2013) Default network activity is a sensitive and specific biomarker of memory in multiple sclerosis. Mult Scler 19(2):199–208CrossRefPubMed
46.
Zurück zum Zitat Morey RA, Petty CM, Xu Y et al (2009) Rebuttal to Hasan and Pedraza in comments and controversies: “Improving the reliability of manual and automated methods for hippocampal and amygdala volume measurements”. Neuroimage 48(3):499–500 Morey RA, Petty CM, Xu Y et al (2009) Rebuttal to Hasan and Pedraza in comments and controversies: “Improving the reliability of manual and automated methods for hippocampal and amygdala volume measurements”. Neuroimage 48(3):499–500
47.
Zurück zum Zitat Cherbuin N, Anstey KJ, Réglade-Meslin C et al (2009) In vivo hippocampal measurement and memory: a comparison of manual tracing and automated segmentation in a large community-based sample. PLoS One 4(4):e5265PubMedCentralCrossRefPubMed Cherbuin N, Anstey KJ, Réglade-Meslin C et al (2009) In vivo hippocampal measurement and memory: a comparison of manual tracing and automated segmentation in a large community-based sample. PLoS One 4(4):e5265PubMedCentralCrossRefPubMed
Metadaten
Titel
Cognitive impairment and memory disorders in relapsing–remitting multiple sclerosis: the role of white matter, gray matter and hippocampus
verfasst von
R. Sacco
A. Bisecco
D. Corbo
M. Della Corte
A. d’Ambrosio
R. Docimo
A. Gallo
F. Esposito
S. Esposito
M. Cirillo
L. Lavorgna
G. Tedeschi
S. Bonavita
Publikationsdatum
01.07.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Neurology / Ausgabe 7/2015
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-015-7763-y

Weitere Artikel der Ausgabe 7/2015

Journal of Neurology 7/2015 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.