Brain atrophy as a marker of cognitive impairment in mildly disabling relapsing–remitting multiple sclerosis
M. P. Sánchez
Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, University of La Laguna, Canary Islands, Spain
Search for more papers by this authorA. Nieto
Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, University of La Laguna, Canary Islands, Spain
Search for more papers by this authorJ. Barroso
Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, University of La Laguna, Canary Islands, Spain
Search for more papers by this authorV. Martín
Servicio de Neuroradiología, Hospital Ntra. Sra. de Candelaria, Canary Islands, Spain
Search for more papers by this authorM. A. Hernández
Servicio de Neurología, Hospital Ntra, Sra. de Candelaria, Canary Islands, Spain
Search for more papers by this authorM. P. Sánchez
Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, University of La Laguna, Canary Islands, Spain
Search for more papers by this authorA. Nieto
Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, University of La Laguna, Canary Islands, Spain
Search for more papers by this authorJ. Barroso
Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, University of La Laguna, Canary Islands, Spain
Search for more papers by this authorV. Martín
Servicio de Neuroradiología, Hospital Ntra. Sra. de Candelaria, Canary Islands, Spain
Search for more papers by this authorM. A. Hernández
Servicio de Neurología, Hospital Ntra, Sra. de Candelaria, Canary Islands, Spain
Search for more papers by this authorAbstract
Background and purpose: We have studied the relationship between neuropsychological impairment and magnetic resonance imaging (MRI) measures in mildly disabling relapsing–remitting multiple sclerosis (RRMS).
Methods: We compared measures of lesion burden and atrophy in 52 patients with Expanded Disability Status Scale ≤ 3.0. Neuropsychological testing explored various cognitive domains: attention and processing speed (APS), verbal and visual memory (VerbM; VisM), visual/constructional processes (VC), executive functions and motor programming/coordination. Specific and global index scores were derived to classify patients as deteriorated or not deteriorated by comparing their performance with 51 matched normal control subjects. Brain MRI analysis included proton density (PD)-lesion volume and T1-hypointensity volume, measures of central atrophy, including the third ventricle width, and corpus callosum (CC).
Results: Patients with either APS, MCP or Verbal Learning impairments had a higher ventricular atrophy than unimpaired. The atrophy of the CC was only associated to VisM dysfunction. Patients with VisM deficits had higher lesion load on PD images. After controlling for age and education a higher third ventricle width was the best predictor for global and specific cognitive impairment.
Conclusion: Our results suggest that cognitive impairment in RR patients with mild disease is better explained by atrophic changes than by total lesion load.
References
- 1 Rovaris M, Filippi M, Falautano M, et al. Relation between MR abnormalities and patterns of cognitive impairment in multiple sclerosis. Neurology 1998; 50: 1601–1608.
- 2 Sperling RA, Guttmann CRG, Hohol MJ, et al. Regional magnetic resonance imaging lesion burden and cognitive function in multiple sclerosis. A longitudinal study. Archives of Neurology 2001; 58: 115–121.
- 3 Randolph JJ, Wishart HA, Saykin AJ, et al. FLAIR lesion volume in multiple sclerosis: relation to processing speed and verbal memory. Journal of the International Neuropsychological Society 2005; 11: 205–209.
- 4 Archibald CJ, Wei X, Scott JN, et al. Posterior fossa lesion volume and slowed information processing in multiple sclerosis. Brain 2004; 127: 1526–1534.
- 5 Benedict RH, Zivadinov R, Carone DA, et al. Regional lobar atrophy predicts memory impairment in multiple sclerosis. American Journal of Neuroradiology 2005; 26: 1824–1831.
- 6 Comi G, Rovaris M, Falautano M, et al. A multiparametric MRI study of frontal lobe dementia in multiple sclerosis. Journal of the Neurological Sciences 1999; 171: 135–144.
- 7 Zivadinov R, De Masi R, Nasuelli D, et al. MRI techniques and cognitive impairment in the early phase of relapsing–remitting multiple sclerosis. Neuroradiology 2001; 43: 272–278.
- 8 Lazeron RH, Boringa JB, Schouten M, et al. Brain atrophy and lesion load as explaining parameters for cognitive impairment in multiple sclerosis. Multiple Sclerosis 2005; 11: 524–531.
- 9 Benedict RH, Bruce JM, Dwyer MG, et al. Neocortical atrophy, third ventricular width, and cognitive dysfunction in multiple sclerosis. Archives of Neurology 2006; 63: 1301–1306.
- 10 Hildebrandt H, Hahn HK, Kraus JA, et al. Memory performance in multiple sclerosis patients correlates with central brain atrophy. Multiple Sclerosis 2006; 12: 428–436.
- 11 Lazeron RH, De Sonneville LM, Scheltens P, Polman CH, Barkhof F. Cognitive slowing in multiple sclerosis is strongly associated with brain volume reduction. Multiple Sclerosis 2006; 12: 760–768.
- 12 Morgen K, Sammer G, Courtney SM, et al. Evidence for a direct association between cortical atrophy and cognitive impairment in relapsing–remitting MS. Neuroimage 2006; 30: 891–898.
- 13 Portaccio E, Amato MP, Bartolozzi ML, et al. Neocortical volume decrease in relapsing–remitting multiple sclerosis with mild cognitive impairment. Journal of the Neurological Sciences 2006; 245: 195–199.
- 14 Sanfilipo MP, Benedict RH, Weinstock-Guttman B, Bakshi R. Gray and white matter brain atrophy and neuropsychological impairment in multiple sclerosis. Neurology 2006; 66: 685–692.
- 15 Tekok-Kilic A, Benedict RH, Weinstock-Guttman B, et al. Independent contributions of cortical gray matter atrophy and ventricle enlargement for predicting neuropsychological impairment in multiple sclerosis. Neuroimage 2007; 36: 1294–1300.
- 16 Lanz M, Hahn HK, Hildebrandt H. Brain atrophy and cognitive impairment in multiple sclerosis: a review. Journal of Neurology 2007; 254(Suppl. 2): II43–II48.
- 17 Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Annals of Neurology 1983; 13: 227–231.
- 18 Kurtzke JF. Rating neurologic impairment in multiple scleroris: an expanded disability status scale (EDSS). Neurology (Cleveland) 1983; 33: 1444–1452.
- 19 Folstein MF, Folstein SE, McHugh PR. Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 1975; 49: 189–198.
- 20 Wechsler D. WAIS-R Manual. New York: The Psychological Corporation, 1981.
- 21 Benton AL, Hamsher K. Multilingual Aphasia Examination, 2nd edn. Iowa City: Department of Neurology and Psychology, The University of Iowa, 1989.
- 22 Kaplan EF, Goodglass H, Weintraub S. The Boston Naming Test. Philadelphia: Lea y Febiger, 1983.
- 23 Beck A. Beck Depression Inventory. San Antonio, TX: The Psychological Corporation, 1978.
- 24 Smith A. Symbol Digit Modalities Test (SDMT). Manual (Revised). Los Angeles: Western Psychological Services, 1982.
- 25 Golden CJ. Stroop Color and Word Test. A Manual for Clinical and Experimental Uses. Illinois: Stoelting Company, 1978.
- 26 Wechsler D. Wechsler Memory Scale Revise-Manual. New York: Psychological Corporation, 1987.
- 27 Gronwall D. Paced auditory serial addition task: a measure of recovery from concussion. Perceptual and Motor Skills 1977; 44: 367–373.
- 28 Schuhfried G. Vienna Reaction Unit (Manual). Vienna, Austria: Schuhfried Ges.m.b.H., 1992.
- 29 Delis DC, Kramer JH, Kaplan E, Ober BA. California Verbal Learning Test. Research Edition Manual. New York: Psychological Corporation, 1987.
- 30 Benton AL. Test de Retention Visuelle. Paris: Les Editions du Centre de Psychologie Appliqueé, 1953.
- 31 Barbizet J, Cany E. Clinical and psychometrical study of a patient with memory disturbances. International Journal of Neurology 1968; 7: 44–54.
- 32 Rao SM, Hammeke TA, McQuillen MP, Khatri BO, Lloyd D. Memory disturbance in chronic progressive multiple sclerosis. Archives of Neurology 1984; 41: 625–631.
- 33 Benton AL, Sivan AB, Hamsher K de S, Varney NR, Spreen O. Contributions to Neuropsychological Assessment: A Clinical Manual, 2nd edn. New York, NY: Oxford University Press, 1994.
- 34 Hooper HE. Hooper Visual Organization Test (VOT). Los Angeles, CA: Western Psychological Services, 1983.
- 35 Rao SM. Cognitive Functions Study Group. A Manual for the Core Battery of Neuropsychological Tests in Multiple Sclerosis. WI: National Multiple Sclerosis Society, 1989.
- 36 Heaton RK. Wisconsin Card Sorting Test Manual. Odessa, FL: Psychological Assessement Resources, 1981.
- 37 Benton AL, Sivan AB, Hamsher K deS, Varney NR, Spreen O. Multilingual Aphasia Examination. Iowa City, IA: University of Iowa, 1976.
- 38 Schuhfried G. Motor Performance Test Series (Manual). Mödling, Austria: Schuhfried Ges.m.b.H., 1992.
- 39 Bermel RA, Bakshi R, Tjoa C, Puli SR, Jacobs L. Bicaudate ratio as a magnetic resonance imaging marker of brain atrophy in multiple sclerosis. Archives of Neurology 2002; 59: 275–280.
- 40 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. Archives of Neurology 2004; 61: 226–230.
- 41 Turner B, Ramli N, Blumhardt LD, Jaspan T. Ventricular enlargement in multiple sclerosis: a comparison of three-dimensional and linear MRI estimates. Neuroradiology 2001; 43: 608–614.
- 42 Rao SM, Leo GJ, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns and prediction. Neurology 1991; 41: 685–691.
- 43 Wishart H, Sharpe D. Neuropsychological aspects of multiple sclerosis: a quantitative review. Journal of Clinical and Experimental Neuropsychology 1997; 19: 810–824.
- 44 Deloire MS, Salort E, Bonnet M, et al. Cognitive impairment as marker of diffuse brain abnormalities in early relapsing remitting multiple sclerosis. Journal of Neurology, Neurosurgery and Psychiatry 2005; 76: 519–526.
- 45 Minden SL, Moes EJ, Orav J, Kaplan E, Reich P. Memory impairment in multiple sclerosis. Journal of Clinical and Experimental Neuropsychology 1990; 12: 566–586.
- 46 Beatty WW, Monson N. Picture and motor sequencing in multiple sclerosis. Journal of Clinical and Experimental Neuropsychology 1994; 16: 165–172.
- 47 Gaudino EA, Chiaravalloti ND, DeLuca J, Diamond BJ. A comparison of memory performance in relapsing–remitting, primary progressive and secondary progressive, multiple sclerosis. Neuropsychiatry, Neuropsychology, & Behavioral Neurology 2001; 14: 32–44.
- 48 Olivares T, Nieto A, Sánchez MP, Wollmann T, Hernández MA, Barroso J. Pattern of neuropsychological impairment in the early phase of relapsing–remitting multiple sclerosis. Multiple Sclerosis 2005; 11: 191–197.
- 49 Landrø´ NI, Celins EG, Sletvold H. Depressive symptoms account for deficient information processing speed but not for impaired working memory in early phase multiple sclerosis. Journal of the Neurological Sciences 2004; 217: 211–216.
- 50 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.
- 51 Huber SJ, Bornstein RA, Rammohan KW, Christy JA, Chakeres DW, McGhee RB. Magnetic resonance imaging correlates of neuropsychological impairment in multiple sclerosis. The Journal of Neuropsychiatry and Clinical Neurosciences 1992; 4: 152–158.
- 52 Swirsky-Sacchetti T, Mitchell DR, Seward J, et al. Neuropsychological and structural brain lesions in MS: a regional analysis. Neurology 1992; 42: 1291–1295.
- 53 Edwards SGM, Liu C, Blumhardt LD. Cognitive correlates of supratentorial atrophy on MRI in multiple sclerosis. Acta Neurologica Scandinavica 2001; 104: 214–223.
- 54 Brass SD, Benedict RH, Weinstock-Guttman B, Munschauer F, Bakshi R. Cognitive impairment is associated with subcortical magnetic resonance imaging grey matter T2 hypointensity in multiple sclerosis. Multiple Sclerosis 2006; 12: 437–444.
- 55 Christodoulou C, Krupp LB, Liang Z, et al. Cognitive performance and MR markers of cerebral injury in cognitively impaired MS patients. Neurology 2003; 60: 1793–1798.
- 56 Simon JH. Brain atrophy in multiple sclerosis: what we know and would like to know. Multiple Sclerosis 2006; 12: 679–687.
- 57 Filippi M, Bozzali M, Rovaris M, et al. Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis. Brain 2003; 126: 433–437.
- 58 Houtchens MK, Benedict RH, Killiany R, et al. Thalamic atrophy and cognition in multiple sclerosis. Neurology 2007; 69: 1213–1223.
