Neurological Sciences

, Volume 37, Issue 2, pp 165–179 | Cite as

Relationship between brain volume loss and cognitive outcomes among patients with multiple sclerosis: a systematic literature review

  • Timothy Vollmer
  • Lynn Huynh
  • Caroline Kelley
  • Philip Galebach
  • James Signorovitch
  • Allitia DiBernardo
  • Rahul Sasane
Review Article


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.


Multiple 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.

Compliance with ethical standards

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.


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Copyright information

© Springer-Verlag Italia 2015

Authors and Affiliations

  • Timothy Vollmer
    • 1
  • Lynn Huynh
    • 2
  • Caroline Kelley
    • 2
  • Philip Galebach
    • 2
  • James Signorovitch
    • 2
  • Allitia DiBernardo
    • 3
  • Rahul Sasane
    • 3
  1. 1.Department of NeurologyUniversity of Colorado DenverAuroraUSA
  2. 2.Analysis Group, Inc.BostonUSA
  3. 3.Novartis Pharmaceuticals CorporationEast HannoverUSA

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