Thomas H. Bak, Siddharthan Chandran and Peter Connick
Background: Impairment of visual cognition occurs in up to 25% of patients with MS, however data on progressive disease is limited and the neural basis remains unknown.
Objective: To evaluate the influence of multifocal inflammatory CNS white matter demyelination burden on visual cognition in equivalent SPMS and PPMS cohorts.
Methods: 59 SPMS and 27 PPMS patients matched for demographic and disease characteristics were evaluated using visuospatial and visuoperceptual components of the Addenbrooke’s cognitive examination-revised (ACE-R) battery. Factors influencing performance were then identified by logistic regression. Exploratory logistic models were also used to determine the predictive value of deficits in attention, working memory, and arithmetic abilities. Finally, comparison of deficits between equivalent primary (PPMS) and secondary (SPMS) progressive disease groups was used to evaluate a potential dose-response for cumulative multifocal inflammatory CNS white matter demyelination.
Results: The overall prevalence of impairment in visual cognition was 14.0% (95%CI=6.4 to 21.4%) with no difference between disease groups. Qualitatively, the observed deficits in visual cognition were subtle, and patients were not able to predict them. Impairment was more common in women (OR 3.2; 95% CI=0.8 to 13.2), and subjects with a Beck depression inventory II score ≥ 25 (OR 5.2; 95% CI=1.1 to 24.2). No effect was seen for: age, years in full-time education, disease duration, clinical evidence of anterior visual pathway dysfunction, or motor disability. Exploratory analyses showed no predictive association with deficits in attention or working memory, however impairment of basic arithmetic skills was a highly significant predictor of impaired visual cognition (OR 29.4, 95% CI 3.0 to 291.9). Allowing for all significant predictors, secondary and primary progressive disease groups had equivalent rates of impairment (OR 1.6, 95% CI 0.4 to 7.1; p=0.538).
Conclusions: Impairment of visual cognition in progressive MS is more common in women and patients with high levels of depressive symptomatology, but occurs independently from anterior visual pathway dysfunction and the cumulative burden of inflammatory CNS white matter demyelination. These findings suggest that the site rather than the absolute quantity of brain pathology is crucial, with the strong association observed to impairment of basic arithmetic skills implicating possible localization to the intraparietal sulcus.