Visual deficits and cognitive assessment of multiple sclerosis: confounder, correlate, or both?

Dejan Jakimovski, Ralph H.B. Benedict, Bianca Weinstock-Guttman, Osman Ozel, Tom A. Fuchs, Norah Lincoff, Niels Bergsland, Michael G. Dwyer, Robert Zivadinov

Research output: Contribution to journalArticlepeer-review


Background: The relationship between visual impairment and cognitive performance in multiple sclerosis (MS) remains poorly understood. Objective: To determine associations between visual acuity and optical coherence tomography (OCT) measures with cognitive performance of MS patients and healthy controls (HCs). Methods: 141 MS patients (with and without MS optic neuritis; MSON) and 50 HCs underwent neuropsychological, visual, and OCT testing. California Verbal Learning Test (CVLT-II), Brief Visuospatial Memory Test (BVMT-R), and Symbol Digit Modalities Test (SDMT) were used. Patients with test performance below − 1.5 standard deviations of the mean HCs scores were labeled as cognitive impairment. Visual ability was assessed with 100%, 2.5%, and 1.25% low-contrast letter acuity (LCLA) charts. OCT-derived peripapillary retinal nerve fiber layer (pRNFL) thickness, macular volume (MV), macular ganglion cell inner plexiform (mGCIP) thickness (as a sum of GC and IP layers), and macular inner nuclear layer (mINL) were computed. Results: 100% and 2.5% LCLA associated with SDMT in MS and HCs (p < 0.001; and p < 0.012, respectively). In MSON patients, visually demanding tests were explained by pRNFL and macular volume for SDMT (β = 0.172, p = 0.039 and β = 0.27, p = 0.001) and MV for BVMT-R (β = 0.21, p = 0.012). In non-MSON, only mINL was predictor of CVLT-II. pRNFL and MV predicted cognitive impairment with an accuracy of 72.2% (Negelkerke R2 = 0.234). These findings were driven by associations within the progressive MS subgroup. HC’s SDMT performance was explained by mGCIP (β = 0.316, p = 0.001). Conclusions: Both LCLA and OCT-based measures (pRNFL and macular volume) were associated with MS cognitive performance. OCT-based measures were also significant predictors of cognitive status in MS patients. mGCIP associated with cognitive performance in HCs.

Original languageEnglish
JournalJournal of Neurology
Publication statusAccepted/In press - 2021


  • Cognitive performance
  • GCIP
  • Low-contrast letter acuity
  • Macular volume
  • Multiple sclerosis
  • Optical coherence tomography
  • RNFL

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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