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Multiple Sclerosis, Vol. 12, No. 6, 760-768 (2006)
DOI: 10.1177/1352458506070924
© 2006 SAGE Publications

Cognitive slowing in multiple sclerosis is strongly associated with brain volume reduction

R HC Lazeron

Department of Neurology, MS-Center, Vrije Universiteit Medical Center, Amsterdam, The Netherlands, rhc.lazeron{at}vumc.nl

L MJ de Sonneville

Department of Clinical Child and Adolescent Studies, Leiden University, Leiden, The Netherlands

P Scheltens

Department of Neurology, MS-Center, Vrije Universiteit Medical Center, Amsterdam, The Netherlands

C H Polman

Department of Neurology, MS-Center, Vrije Universiteit Medical Center, Amsterdam, The Netherlands

F Barkhof

Department of Radiology, MS-Center, Vrije Universiteit Medical Center, Amsterdam, The Netherlands

Introduction In this study, we investigated the influence of in vivo disease pathology (measured as magnetic resonance imaging (MRI) lesion load and brain volume reduction) on cognitive functioning, especially the speed of processing, in multiple sclerosis (MS) patients. Since MS is characterized by cognitive slowing rather than impaired accuracy, we used the Amsterdam Neuropsychological Tasks (ANT) program, a computerized test proven to be very sensitive to cognitive slowing in MS patients.

Methods Thirty-two patients performed the ANT and underwent MRI scanning. Using the ANT computerized tests, we investigated focused, divided, sustained attention, executive function and psychomotor function, and examined associations of speed, speed fluctuation and accuracy of performance of these tests with MRI lesion load and brain volume parameters.

Results A decrease in the speed of processing and response speed stability, and a decrease in psychomotor accuracy and stability were clearly associated with less brain volume, and with higher lesion loads, in particular at frontal and occipital areas. Correlations with brain volume reduction were found for all domains, except for visuo-spatial processing. In particular, speed and speed fluctuation scores correlated with brain volume reduction, while accuracy of performance, in general, did not correlate. Only some test speed scores and speed fluctuation scores correlated with lesion load measurements.

Conclusion This study shows that, in MS patients, accuracy of processing is not compromised unless high working memory demands are involved. Problems in neurocognitive functioning in MS are mainly modulated by speed and stability of speed processing, in particular when attention-demanding controlled information processing is required. Abnormalities in these domains are most strongly associated with brain volume loss, confirming that pathology beyond focal lesions is important in MS.

Key Words: ANT • magnetic resonance • multiple sclerosis • neuropsychology

References

  • Beatty PA, Gange JJ. Neuropsychological aspects of multiple sclerosis . J Nerv Ment Dis 1977; 164: 42-50 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Rao SM. Neuropsychology of multiple sclerosis: a critical review . J Clin Exp Neuropsychol 1986; 8: 503-542 .[ISI][Medline] [Order article via Infotrieve]
  • Rao SM, Leo GJ, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction . Neurology 1991; 41: 685-691 .[ISI][Medline] [Order article via Infotrieve]
  • Wishart H, Sharpe D. Neuropsychological aspects of multiple sclerosis: a quantitative review . J Clin Exp Neuropsychol 1997; 19: 810-824 .[ISI][Medline] [Order article via Infotrieve]
  • De Sonneville LMJ, Boringa JB, Reuling IEW, Lazeron RHC, Ader HJ, Polman CH. Information processing characteristics in subtypes of multiple sclerosis . Neuropsychologia 2002; 40: 1751-1765 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • De Sonneville LMJ. Amsterdam Neuropsychological Task: a computer-aided assessment program. In 6 Cognitive ergonomics, clinical assessment and computer-assisted learning: computers in psychology. Swets & Zeitlinger , 1999: 187-203.
  • De Sonneville LMJ. Amsterdam Neuropsychological Tasks: scientific and clinical applications (Amsterdamse Neuropsychologische Taken: wetenschappelijke en klinische toepassingen) . Ned Tijdschr Neuropsychol 2005; 1: 27-41 .
  • Kujala P, Portin R, Revonsuo A, Ruutiainen J. Automatic and controlled information processing in multiple sclerosis . Brain 1994; 117: 1115-1126 .[Abstract/Free Full Text]
  • Kail R. The neural noise hypothesis: evidence from processing speed in adults with multiple sclerosis . Aging Neuropsychol Cogn 1997; 4: 157-165 .
  • Kail R. Speed of information processing in patients with multiple sclerosis . J Clin Exp Neuropsychol 1998; 20: 98-106 .[ISI][Medline] [Order article via Infotrieve]
  • Comi G, Martinelli V. Pathophysiology of cognitive impairment in multiple sclerosis . Ital J Neurol Sci 1998; 19: S443-S447 .[CrossRef]
  • Davie CA, Barker GJ, Thompson AJ, Tofts PS, McDonald WI, Miller DH. H-1 magnetic resonance spectroscopy of chronic cerebral white matter lesions and normal appearing white matter in multiple sclerosis . J Neurol Neurosurg Psychiatry 1997; 63: 736-742 .[Abstract/Free Full Text]
  • Huijbregts SCJ, De Sonneville LMJ, Van Spronsen FJ, Licht R, Sergeant JA. The neuropsychological profile of early and continuously treated phenylketonuria: orienting, vigilance, and maintenance versus manipulation-functions of working memory . Neurosci Biobehav Rev 2002; 26: 697-712 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Kalff AC, De Sonneville LMJ, Hurks PPM, Hendriksen JGM, Kroes M, Feron FJMet al. Low-and high-level controlled processing in executive motor control tasks in 5-6-year-old children at risk of ADHD . J Child Psychol Psychiatry Allied Discipl 2003; 44: 1049-1057 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • van Walderveen MAA, Barkhof F, Hommes OR, Polman CH, Tobi H, Frequin SMet al. Correlating MRI and clinical disease activity in multiple sclerosis-relevance of hypointense lesions on short-TR short-TE (T-1-weighted) spin-echo images . Neurology 1995; 45: 1684-1690 .[Abstract/Free Full Text]
  • Lazeron RHC, Boringa JB, Schouten M, Uitdehaag BMJ, Bergers E, Lindeboom Jet al. Brain atrophy and lesion load as explaining parameters for cognitive impairment in multiple sclerosis . Mult Scler 2005; 11: 524-531 .[Abstract/Free Full Text]
  • Kalkers NF, Vrenken H, Uitdehaag BMJ, Polman CH, Barkhof F. Brain atrophy in multiple sclerosis: impact of lesions and of damage of whole brain tissue . Mult Scler 2002; 8: 410-414 .[Abstract/Free Full Text]
  • Trefz F, Desonneville L, Matthis P, Benninger C, Lanzenglert B, Bickel H. Neuropsychological and biochemical investigations in heterozygotes for phenylketonuria during ingestion of high-dose aspartame (a sweetener containing phenylalanine) . Hum Gen 1994; 93: 369-374 .[ISI][Medline] [Order article via Infotrieve]
  • Schmidt E, Rupp A, Burgard P, Pietz J, Weglage J, Desonneville L. Sustained attention in adult phenylketonuria-the influence of the concurrent phenylala-nine-blood-level . J Clin Exp Neuropsychol 1994; 16: 681-688 .[ISI][Medline] [Order article via Infotrieve]
  • Jennekens-Schinkel A, Sanders EA, Lanser JB, van der Velde EA. Reaction time in ambulant multiple sclerosis patients. Part II. Influence of task complexity . J Neurol Sci 1988; 85: 187-196 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Jennekens-Schinkel A, Sanders EA, Lanser JB, van der Velde EA. Reaction time in ambulant multiple sclerosis patients. Part I. Influence of prolonged cognitive effort . J Neurol Sci 1988; 85: 173-186 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Rao SM, St Aubin-Faubert P, Leo GJ. Information processing speed in patients with multiple sclerosis . J Clin Exp Neuropsychol 1989; 11: 471-477 .[ISI][Medline] [Order article via Infotrieve]
  • Franklin GM, Heaton RK, Nelson LM, Filley CM, Seibert C. Correlation of neuropsychological and MRI findings in chronic/progressive multiple sclerosis . Neurology 1988; 38: 1826-1829 .[Abstract/Free Full Text]
  • Rao SM, Leo GJ, Haughton VM, St Aubin-Faubert P, Bernardin L. Correlation of magnetic resonance imaging with neuropsychological testing in multiple sclerosis . Neurology 1989; 39: 161-166 .[Abstract/Free Full Text]
  • Swirsky-Sacchetti T, Mitchell DR, Seward J, Gonzales C, Lublin F, Knobler Ret al. Neuropsychological and structural brain lesions in multiple sclerosis: a regional analysis . Neurology 1992; 42: 1291-1295 .[Abstract/Free Full Text]
  • Arnett PA, Rao SM, Bernardin L, Grafman J, Yetkin FZ, Lobeck L. Relationship between frontal lobe lesions and Wisconsin Card Sorting Test performance in patients with multiple sclerosis . Neurology 1994; 44: 420-425 .[ISI]
  • Hohol MJ, Guttmann CR, Orav J, Mackin GA, Kikinis R, Khoury SJet al. Serial neuropsychological assessment and magnetic resonance imaging analysis in multiple sclerosis . Arch Neurol 1997; 54: 1018-1025 .[Abstract]
  • Rovaris M, Filippi M, Falautano M, Minicucci L, Rocca MA, Martinelli Vet al. Relation between MR abnormalities and patterns of cognitive impairment in multiple sclerosis . Neurology 1998; 50: 1601-1608 .[Abstract]
  • Lazeron RHC, Langdon DW, Filippi M, van Waesberghe JHTM, Stevenson VL, Boringa JBSet al. Neuropsychological impairment in multiple sclerosis patients: the role of (juxta)cortical lesion on FLAIR . Mult Scler 2000; 6: 280-285 .[Abstract/Free Full Text]
  • Huber SJ, Paulson GW, Shuttleworth EC, Chakeres D, Clapp LE, Pakalnis Aet al. Magnetic resonance imaging correlates of dementia in multiple sclerosis . Arch Neurol 1987; 44: 732-736 .[Abstract]
  • Mariani C, Farina E, Cappa SF, Anzola GP, Faglia L, Bevilacqua Let al. Neuropsychological assessment in multiple sclerosis: a follow-up study with magnetic resonance imaging . J Neurol 1991; 238: 395-400 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Patti F, Failla G, Ciancio MR, Lepiscopo MR, Reggio A. Neuropsychological, neuroradiological and clinical findings in multiple sclerosis-a 3 year follow-up study . Eur J Neurol 1998; 5: 283-286 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Demaree HA, Deluca J, Gaudino EA, Diamond BJ. Speed of information processing as a key deficit in multiple sclerosis: implications for rehabilitation . J Neurol Neurosurg Psychiatry 1999; 67: 661-663 .[Abstract/Free Full Text]
  • Jonsson A, Korfitzen EM, Heltberg A, Ravnborg MH, Byskovottosen E. Effects of neuropsychological treatment in patients with multiple sclerosis . Acta Neurol Scand 1993; 88: 394-400 .[ISI][Medline] [Order article via Infotrieve]
  • Benedict RHB, Weinstock-Guttman B, Fishman I, Sharma J, Tjoa CW, Bakshi R. Prediction of neuropsychological impairment in multiple sclerosis-comparison of conventional magnetic resonance imaging measures of atrophy and lesion burden . Arch Neurol 2004; 61: 226-230 .[Abstract/Free Full Text]
  • Filippi M, Rocca MA, Martino G, Horsfield MA, Comi G. Magnetization transfer changes in the normal appearing white matter precede the appearance of enhancing lesions in patients with multiple sclerosis . Ann Neurol 1998; 43: 809-814 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • van Waesberghe JHTM, Castelijns JA, Lazeron RHC, Nijeholt GJLA, Barkhof F. Magnetization transfer contrast (MTC) and long repetition time spin-echo MR imaging in multiple sclerosis . Magn Res Imag 1998; 16: 351-358 .
  • Benedict RHB, Bakshi R, Simon JH, Priore R, Miller C, Munschauer F. Frontal cortex atrophy predicts cognitive impairment in multiple sclerosis . J Neuropsychiatry Clin Neurosci 2001; 14: 44-51 .

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