Cognitive decline in multiple sclerosis: impact of topographic lesion distribution on differential cognitive deficit patterns

Background: Multiple sclerosis (MS) is often accompanied by cognitive dysfunction. A negative correlation between cerebral lesion load and atrophy and cognitive performance has been pointed out almost consistently. Further, the distribution of lesions might be critical for the emergence of specific patterns of cognitive deficits. Objective: The current study evaluated the significance of total lesion area (TLA) and central atrophy for the prediction of general cognitive dysfunction and tested for a correspondence between lesion topography and specific cognitive deficit patterns. Methods: Thirty-seven patients with MS underwent neuropsychological assessment and magnetic resonance imaging. Lesion burden and central atrophy were quantified. Patients were classified into three groups by means of individual lesion topography (punctiform lesions/periventricular lesions/confluencing lesions in both periventricular and extra-periventricular regions). Results: TLA was significantly related to 7 cognitive variables, whereas third ventricle width was significantly associated with 20 cognitive parameters. The three groups differed significantly in their performances on tasks concerning alertness, mental speed, and memory function. Conclusion: Third ventricle width as a straight-forward measure of central atrophy proved to be of substantial predictive value for cognitive dysfunction, whereas total lesion load played only a minor role. Periventricular located lesions were significantly related to decreased psychomotor speed, whereas equally distributed cerebral lesion load did not. These findings support the idea that periventricular lesions have a determinant impact on cognition in patients with MS.