Cognitive impairment and magnetic resonance imaging correlates in primary progressive multiple sclerosis
Corresponding Author
A. Gouveia
Department of Neurology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
Correspondence
A. Gouveia, Department of Neurology, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, Coimbra, Portugal.
Email: [email protected]
Search for more papers by this authorS. P. Dias
Department of Neurology, Centro Hospitalar de Lisboa Central, Lisboa, Portugal
Search for more papers by this authorT. Santos
Department of Neurology, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal
Search for more papers by this authorH. Rocha
Department of Neurology, Centro Hospitalar de São João, Porto, Portugal
Faculty of Medicine, Department of Clinical Neuroscience and Mental Health, University of Porto, Porto, Portugal
Search for more papers by this authorC. R. Coelho
Department of Neurology, Centro Hospitalar de Setúbal, Setúbal, Portugal
Search for more papers by this authorL. Ruano
Department of Neurology, Centro Hospitalar Entre Douro e Vouga, Santa Maria da Feira, Portugal
EPIUnit – Epidemiology Research Unit, Institute of Public Health, University of Porto, Porto, Portugal
Search for more papers by this authorO. Galego
Department of Neuroradiology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
Search for more papers by this authorM. C. Diogo
Department of Neuroradiology, Centro Hospitalar de Lisboa Central, Lisboa, Portugal
Search for more papers by this authorD. Seixas
Department of Imaging Diagnosis, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal
Faculty of Medicine, Department of Experimental Biology, Porto University, Porto, Portugal
Search for more papers by this authorM. J. Sá
Department of Neurology, Centro Hospitalar de São João, Porto, Portugal
Faculty of Health Sciences, University Fernando Pessoa, Porto, Portugal
Search for more papers by this authorS. Batista
Department of Neurology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
Faculty of Medicine, University of Coimbra, Coimbra, Portugal
Search for more papers by this authorCorresponding Author
A. Gouveia
Department of Neurology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
Correspondence
A. Gouveia, Department of Neurology, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, Coimbra, Portugal.
Email: [email protected]
Search for more papers by this authorS. P. Dias
Department of Neurology, Centro Hospitalar de Lisboa Central, Lisboa, Portugal
Search for more papers by this authorT. Santos
Department of Neurology, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal
Search for more papers by this authorH. Rocha
Department of Neurology, Centro Hospitalar de São João, Porto, Portugal
Faculty of Medicine, Department of Clinical Neuroscience and Mental Health, University of Porto, Porto, Portugal
Search for more papers by this authorC. R. Coelho
Department of Neurology, Centro Hospitalar de Setúbal, Setúbal, Portugal
Search for more papers by this authorL. Ruano
Department of Neurology, Centro Hospitalar Entre Douro e Vouga, Santa Maria da Feira, Portugal
EPIUnit – Epidemiology Research Unit, Institute of Public Health, University of Porto, Porto, Portugal
Search for more papers by this authorO. Galego
Department of Neuroradiology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
Search for more papers by this authorM. C. Diogo
Department of Neuroradiology, Centro Hospitalar de Lisboa Central, Lisboa, Portugal
Search for more papers by this authorD. Seixas
Department of Imaging Diagnosis, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal
Faculty of Medicine, Department of Experimental Biology, Porto University, Porto, Portugal
Search for more papers by this authorM. J. Sá
Department of Neurology, Centro Hospitalar de São João, Porto, Portugal
Faculty of Health Sciences, University Fernando Pessoa, Porto, Portugal
Search for more papers by this authorS. Batista
Department of Neurology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
Faculty of Medicine, University of Coimbra, Coimbra, Portugal
Search for more papers by this authorAbstract
Objectives
To characterize cognitive impairment in primary progressive multiple sclerosis (PPMS) and to correlate the pattern of cognitive deficits with brain magnetic resonance imaging (MRI) volumetric data.
Materials and methods
In a multicenter cross-sectional study, we recruited consecutive patients with PPMS as well as age, sex, and education level-matched healthy controls (HC). All participants underwent neuropsychological (NP) assessment, and brain MRI was performed in patients with PPMS for analysis of lesion load, subcortical GM volumes, and regional cortical volumes.
Results
We recruited 55 patients with PPMS and 36 HC. Thirty-six patients were included in the MRI analysis. Patients with PPMS performed significantly worse than HC in all NP tests. Subcortical GM volume was significantly correlated with all NP tests, except for Stroop Test, with the largest effect for the thalamus (r=−.516 [BVMT-R DR, P=.016 FDR-corrected] to r=.664 [SDMT, P<.001 FDR-corrected]). In the stepwise linear regression model, thalamic volume was the only predictor of performance in all NP tests.
Conclusion
Cognitive impairment is common in PPMS and affects all evaluated cognitive domains. Subcortical GM volume, particularly of the thalamus, is a strong predictor of cognitive performance, suggesting it has a central role in the pathophysiology of PPMS-related cognitive dysfunction.
Supporting Information
| Filename | Description |
|---|---|
| ane12702-sup-0001-TableS1.docxWord document, 12.7 KB |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1Amato MP, Zipoli V, Portaccio E. Multiple sclerosis-related cognitive changes: a review of cross-sectional and longitudinal studies. J Neurol Sci. 2006; 245: 41–46.
- 2Wachowius U, Talley M, Silver N, Heinze HJ, Sailer M. Cognitive impairment in primary and secondary progressive multiple sclerosis. J Clin Exp Neuropsychol. 2005; 27: 65–77.
- 3Rao SM, Leo GJ, Ellington L, Nauertz T, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. II. Impact on employment and social functioning. Neurology. 1991; 41: 692–696.
- 4Camp SJ, Stevenson VL, Thompson AJ, et al. Cognitive function in primary progressive and transitional progressive multiple sclerosis: a controlled study with MRI correlates. Brain. 1999; 122(Pt 7): 1341–1348.
- 5Huijbregts SC, Kalkers NF, de Sonneville LM, de Groot V, Reuling IE, Polman CH. Differences in cognitive impairment of relapsing remitting, secondary, and primary progressive MS. Neurology. 2004; 63: 335–339.
- 6Gajofatto A, Turatti M, Bianchi MR, et al. Benign multiple sclerosis: physical and cognitive impairment follow distinct evolutions. Acta Neurol Scand. 2016; 133: 183–191.
- 7Miller DH, Leary SM. Primary-progressive multiple sclerosis. Lancet Neurol. 2007; 6: 903–912.
- 8Rosti-Otajärvi E, Ruutiainen J, Huhtala H, Hämäläinen P. Relationship between subjective and objective cognitive performance in multiple sclerosis. Acta Neurol Scand. 2014; 130: 319–327.
- 9Foong J, Rozewicz L, Chong WK, Thompson AJ, Miller DH, Ron MA. A comparison of neuropsychological deficits in primary and secondary progressive multiple sclerosis. J Neurol. 2000; 247: 97–101.
- 10De Sonneville LM, Boringa JB, Reuling IE, Lazeron RH, Ader HJ, Polman CH. Information processing characteristics in subtypes of multiple sclerosis. Neuropsychologia. 2002; 40: 1751–1765.
- 11Ruet A, Deloire M, Charre-Morin J, Hamel D, Brochet B. Cognitive impairment differs between primary progressive and relapsing-remitting MS. Neurology. 2013; 80: 1501–1508.
- 12Hanssen KT, Beiske AG, Landro NI, Hessen E. Predictors of executive complaints and executive deficits in multiple sclerosis. Acta Neurol Scand. 2014; 129: 234–242.
- 13Batista S, Zivadinov R, Hoogs M, et al. Basal ganglia, thalamus and neocortical atrophy predicting slowed cognitive processing in multiple sclerosis. J Neurol. 2012; 259: 139–146.
- 14Filippi M, Rovaris M, Rocca MA. Imaging primary progressive multiple sclerosis: the contribution of structural, metabolic, and functional MRI techniques. Mult Scler. 2004; 10(Suppl 1): S36–S44. discussion S-5.
- 15Ukkonen M, Vahvelainen T, Hamalainen P, Dastidar P, Elovaara I. Cognitive dysfunction in primary progressive multiple sclerosis: a neuropsychological and MRI study. Mult Scler. 2009; 15: 1055–1061.
- 16Tur C, Penny S, Khaleeli Z, et al. Grey matter damage and overall cognitive impairment in primary progressive multiple sclerosis. Mult Scler, 2011; 17: 1324–1332.
- 17Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria. Ann Neurol. 2011; 69: 292–302.
- 18Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983; 33: 1444–1452.
- 19Smith A. Symbol Digit Modalities Test: Manual. Los Angeles, CA: Western Psychological Services; 1982.
- 20Rao SM. A Manual for the Brief. Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis: National Multiple Sclerosis Society; 1991.
- 21Benedict RHB. Brief Visuospatial Memory Test-Revised: Professional Manual. Odessa, FL: Psychological Assessment Resources; 1997.
- 22Delis DC, Kramer JH, Kaplan E, Ober BA. The California Verbal Learning Test. San Antonio, TX: Psychological Corporation; 1987.
- 23Stroop JR. Studies of interference in serial verbal reactions. J Exp Psychol Gen. 1935; 18: 643–662.
10.1037/h0054651 Google Scholar
- 24Greshwater G. The Stroop Color and Word Test: A Manual for Clinical and Experimental Uses. Wood Dale, IL: Stoelting Co.; 2002.
- 25Langdon D, Amato M, Boringa J, et al. Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Mult Scler 2012; 18: 891–898.
- 26Vaz Serra APA JL. Aferição dos quadros depressivos I – Ensaio de aplicação do Inventário Depressivo de Beck a uma amostra portuguesa de doentes deprimidos. Coimbra Médica. 1973; 20: 623–644.
- 27Vaz Serra A, Pio Abreu JL. Aferição dos quadros depressivos II – Estudo preliminar de novos agrupamentos sintomatológicos para complemento do Inventário Depressivo de Beck. Coimbra Médica. 1973; 20: 713–736.
- 28Fisk JD, Pontefract A, Ritvo PG, Archibald CJ, Murray TJ. The impact of fatigue on patients with multiple sclerosis. Can J Neurol Sci. 1994; 21: 9–14.
- 29Dale AM, Fischl B, Sereno MI. Cortical surface-based analysis I. Segmentation and surface reconstruction. NeuroImage. 1999; 9: 179–194.
- 30Fischl B, Sereno MI, Dale AM. Cortical surface-based analysis. II: inflation, flattening, and a surface-based coordinate system. NeuroImage. 1999; 9: 195–207.
- 31Fischl B, Dale AM. Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc Natl Acad Sci U S A. 2000; 97: 11050–11055.
- 32Fischl B, van der Kouwe A, Destrieux C, et al. Automatically parcellating the human cerebral cortex. Cereb Cortex. 2004; 14: 11–22.
- 33Han X, Jovicich J, Salat D, et al. Reliability of MRI-derived measurements of human cerebral cortical thickness: the effects of field strength, scanner upgrade and manufacturer. NeuroImage. 2006; 32: 180–194.
- 34Cohen AB, Neema M, Arora A, et al. The Relationships among MRI-Defined Spinal Cord Involvement, Brain Involvement, and Disability in Multiple Sclerosis. J Neuroimaging. 2012; 22: 122–128.
- 35Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci. 1986; 9: 357–381.
- 36Inglese M, Liu S, Babb JS, Mannon LJ, Grossman RI, Gonen O. Three-dimensional proton spectroscopy of deep gray matter nuclei in relapsing-remitting MS. Neurology. 2004; 63: 170–172.
- 37Sepulcre J, Sastre-Garriga J, Cercignani M, Ingle GT, Miller DH, Thompson AJ. Regional gray matter atrophy in early primary progressive multiple sclerosis: a voxel-based morphometry study. Arch Neurol. 2006; 63: 1175–1180.
- 38Mesaros S, Rocca MA, Pagani E, et al. Thalamic damage predicts the evolution of primary-progressive multiple sclerosis at 5 years. AJNR Am J Neuroradiol 2011; 32: 1016–1020.
- 39Stewart CC, Griffith HR, Okonkwo OC, et al. Contributions of volumetrics of the hippocampus and thalamus to verbal memory in temporal lobe epilepsy patients. Brain Cogn. 2009; 69: 65–72.
