Early imaging predicts later cognitive impairment in primary progressive multiple sclerosis.

Background: Cognitive impairment in primary progressive multiple sclerosis (PPMS) is common and correlates modestly with contemporary lesion burden and brain volume. Using a cohort/case control methodology, we explore the ability of MRI abnormalities, including those in the normal-appearing brain tissue, to predict future cognitive dysfunction in PPMS. Methods: Thirty-one patients recruited into a longitudinal study within 5 years of onset of PPMS were assessed neuropsychologically on average 5.5 years later along with 31 matched healthy controls. MRI data obtained at entry into the study (lesion metrics, brain volumes, magnetization transfer ratio histogram metrics, and magnetic resonance spectroscopy metabolite concentrations) were used to predict cognitive impairment at follow-up. Results: Twenty-nine percent of patients were categorized as cognitively impaired. T2 lesion volume was the best MRI predictor of overall cognitive function and performance on tests of verbal memory and attention/speed of information processing. Low gray matter magnetization transfer ratio was the best predictor of poor performance on a further test of attention/speed of information processing and an executive function test. Low gray and white matter volumes were independent predictors of poor performance on a second test of executive function. Conclusions: MRI abnormalities observed in early primary progressive multiple sclerosis can predict cognitive impairment 5 years later. While focal damage disrupting white matter tracts appears to be the most important predictor of subsequent cognitive dysfunction, gray matter pathology also plays a role.