Relationship between brain volume loss and cognitive outcomes among patients with multiple sclerosis: a systematic literature review
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Patients with multiple sclerosis (MS) experience varying rates of brain volume (BV) loss ranging from 0.5 to 1.5 % per year. In addition, 66 % of patients with MS experience cognitive impairment, resulting in impact on daily activities. A systematic literature review (2003–2013) was conducted to identify all studies reporting a relationship between whole BV measures and selected patient outcomes measuring cognition, including the Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT) and MS Functional Composite (MSFC) scores. We identified 18 studies reporting associations between whole BV and cognitive outcomes. Six studies (33 %) examined the association between BV and SDMT; all six studies reported that BV loss (BVL) was significantly associated with a decline in SDMT scores (all p < 0.05). Among 14 studies (78 %) that examined the association between BV and PASAT scores, 12 (86 %) found a significant relationship between BVL and lower PASAT scores (all p < 0.05). Of the seven studies (39 %) that looked at BV and MSFC, six studies (86 %) found BVL significantly associated with lower MSFC scores (all p < 0.05). Our study demonstrated that BVL is associated with declines in cognition in MS patients across several cognition measures. The results of this study suggest that BV is a critical component of disease activity and progression in MS and has implications for treatment decisions to minimize BVL and preserve cognitive functioning.
KeywordsMultiple sclerosis Patient outcomes Brain volume loss Cognition Systematic literature review
Lynn Huynh, Philip Galebach, and Caroline Kelley contributed to the acquisition, analysis, and interpretation of the data, manuscript development, and approval of the final submitted version. James Signorovitch, Rahul Sasane, Allitia DiBernardo, and Timothy Vollmer conceived and planned the work that led to the manuscript, provided substantive suggestions for revisions, and approved the final submitted version. Dr. Vollmer has received consulting fees, and his institution has received a grant and consulting fee for his participation in the BRAVO study; is the medical director for the Rocky Mountain MS Center; he or his institution has received consultancy fees from Biogen-Idec, Teva, Hoffman-LaRoche, Accelerated Cure Project, Genzyme, Acorda, Novartis, Questor, Medscape, Xenoport, and Sanofi; his institution received fees/Grants from Teva, Biogen Idec, Genzyme, Ono, Eli Lilly, Novartis, BioMS, Orasi, Sanofi-Aventis, NIH, EMD Sorono, Acorda, Accelerated Cure Project, Hoffmann-LaRoche, Jensen Research, Janssen Pharmaceutical, MedImmune, Delta Quest, and Roche/Genentech. He is a co-holder of a patent with Teva Pharmaceuticals.
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Conflict of interest
Lynn Huynh, Caroline Kelley, Phil Galebach, and James Signorovitch are employees of Analysis Group, Inc., a consulting company that has received research Grants from Novartis Pharmaceuticals Corporation. Rahul Sasane is an employee of Novartis Pharmaceuticals Corporation. Allitia DiBernardo was an employee of Novartis Pharmaceuticals Corporation at the time the study was conducted. Financial support for this study was provided by Novartis Pharmaceuticals Corporation.
- 7.Benedict RHB (2011) Cognitive dysfunction in multiple sclerosis. Clinical Bulletin Information for Health Professionals. National Multiple Sclerosis Society, Professional Resource Center. http://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Clinical-Bulletin-Cognitive-Dysfunction-Benedict.pdf
- 9.Achiron A, Chapman J, Magalashvili D, Dolev M, Lavie M, Bercovich E, Polliack M, Doniger GM, Stern Y, Khilkevich O, Menascu S, Hararai G, Gurevich M, Barak Y (2013) Modeling of cognitive impairment by disease duration in multiple sclerosis: a cross-sectional study. PLoS One 8(8):e71058. doi: 10.1371/journal.pone.0071058 PubMedCentralCrossRefPubMedGoogle Scholar
- 10.Achiron A, Polliack M, Rao SM, Barak Y, Lavie M, Appelboim N, Harel Y (2005) Cognitive patterns and progression in multiple sclerosis: construction and validation of percentile curves. J Neurol Neurosurg Psychiatry 76(5):744–749. doi: 10.1136/jnnp.2004.045518 PubMedCentralCrossRefPubMedGoogle Scholar
- 12.Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. Bmj 339. doi: 10.1136/bmj.b2700
- 14.Benedict RH, Bruce JM, Dwyer MG, Abdelrahman N, Hussein S, Weinstock-Guttman B, Garg N, Munschauer F, Zivadinov R (2006) Neocortical atrophy, third ventricular width, and cognitive dysfunction in multiple sclerosis. Arch Neurol 63(9):1301–1306. doi: 10.1001/archneur.63.9.1301 CrossRefPubMedGoogle Scholar
- 16.Benedict RH, Weinstock-Guttman B, Fishman I, Sharma J, Tjoa CW, Bakshi R (2004) Prediction of neuropsychological impairment in multiple sclerosis: comparison of conventional magnetic resonance imaging measures of atrophy and lesion burden. Arch Neurol 61(2):226–230. doi: 10.1001/archneur.61.2.226 CrossRefPubMedGoogle Scholar
- 17.Calabrese M, Agosta F, Rinaldi F, Mattisi I, Grossi P, Favaretto A, Atzori M, Bernardi V, Barachino L, Rinaldi L, Perini P, Gallo P, Filippi M (2009) Cortical lesions and atrophy associated with cognitive impairment in relapsing-remitting multiple sclerosis. Arch Neurol 66(9):1144–1150. doi: 10.1001/archneurol.2009.174 CrossRefPubMedGoogle Scholar
- 19.Furby J, Hayton T, Anderson V, Altmann D, Brenner R, Chataway J, Hughes R, Smith K, Miller D, Kapoor R (2008) Magnetic resonance imaging measures of brain and spinal cord atrophy correlate with clinical impairment in secondary progressive multiple sclerosis. Mult Scler 14(8):1068–1075. doi: 10.1177/1352458508093617 CrossRefPubMedGoogle Scholar
- 20.Hayton T, Furby J, Smith KJ, Altmann DR, Brenner R, Chataway J, Hughes RA, Hunter K, Tozer DJ, Miller DH, Kapoor R (2009) Grey matter magnetization transfer ratio independently correlates with neurological deficit in secondary progressive multiple sclerosis. J Neurol 256(3):427–435. doi: 10.1007/s00415-009-0110-4 CrossRefPubMedGoogle Scholar
- 26.Mineev KK, Prakhova LN, Il’ves AG, Kataeva GV, Petrov AM, Reznikova TN, Pozdnyakov AV, Stolyarov ID (2009) Characteristics of neurological and cognitive status in patients with multiple sclerosis in relation to the location and volumes of demyelination foci and the severity of brain atrophy. Neurosci Behav Physiol 39(1):35–38. doi: 10.1007/s11055-008-9086-2 CrossRefPubMedGoogle Scholar
- 29.Shiee N, Bazin PL, Zackowski KM, Farrell SK, Harrison DM, Newsome SD, Ratchford JN, Caffo BS, Calabresi PA, Pham DL, Reich DS (2012) Revisiting brain atrophy and its relationship to disability in multiple sclerosis. PLoS One 7(5):e37049. doi: 10.1371/journal.pone.0037049 PubMedCentralCrossRefPubMedGoogle Scholar
- 37.Langdon DW, Amato MP, Boringa J, Brochet B, Foley F, Fredrikson S, Hamalainen P, Hartung HP, Krupp L, Penner IK, Reder AT, Benedict RH (2012) Recommendations for a brief international cognitive assessment for multiple sclerosis (BICAMS). Mult Scler 18(6):891–898. doi: 10.1177/1352458511431076 PubMedCentralCrossRefPubMedGoogle Scholar
- 41.Tauhid S, Chu R, Sasane R, Glanz B, Neema M, Miller J, JKim G, Signorivich J, Healy B, Chitnis T, Weiner H, Bakshi R (2014) Brain MRI lesions and atrophy are associated with employment status in patients with multiple sclerosis. Paper presented at the ACTRIMS-ECTRIMS, Boston, MAGoogle Scholar
- 42.Li DK, Held U, Petkau J, Daumer M, Barkhof F, Fazekas F, Frank JA, Kappos L, Miller DH, Simon JH, Wolinsky JS, Filippi M, Sylvia Lawry Centre for MSR (2006) MRI T2 lesion burden in multiple sclerosis: a plateauing relationship with clinical disability. Neurology 66(9):1384–1389. doi: 10.1212/01.wnl.0000210506.00078.5c CrossRefPubMedGoogle Scholar
- 44.Calabrese M, De Stefano N, Atzori M, Bernardi V, Mattisi I, Barachino L, Morra A, Rinaldi L, Romualdi C, Perini P, Battistin L, Gallo P (2007) Detection of cortical inflammatory lesions by double inversion recovery magnetic resonance imaging in patients with multiple sclerosis. Arch Neurol 64(10):1416–1422. doi: 10.1001/archneur.64.10.1416 CrossRefPubMedGoogle Scholar
- 46.Lucchinetti CF, Popescu BF, Bunyan RF, Moll NM, Roemer SF, Lassmann H, Bruck W, Parisi JE, Scheithauer BW, Giannini C, Weigand SD, Mandrekar J, Ransohoff RM (2011) Inflammatory cortical demyelination in early multiple sclerosis. N Engl J Med 365(23):2188–2197. doi: 10.1056/NEJMoa1100648 PubMedCentralCrossRefPubMedGoogle Scholar