​Prof. Sten Fredrikson

Long term cognitive decline in multiple sclerosis

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In multiple sclerosis (MS) there is a scarcity of long-term cognitive studies in combination with long-term neuroimaging evaluations. In a recent study, the long term progression of cognitive dysfunction and its neuroanatomical correlates and predictors were analysed (Ouellette 2018).

A cohort of 37 MS-patients that have been followed for more than 17 years by the same neurologist and neuropsychologist was included. The patients represented all subtypes of the disease and reflected five decades of disease duration. The patients were analysed at onset, after 9 years and after 17.5 years. As expected, there was a switch from mostly relapsing-remitting patients at onset of the study, to mostly secondary-progressive patients at the final follow-up. EDSS was evaluated by the same neurologist at all occasions. Global cognitive functioning was assessed by a standardised neuropsychological test battery, including symbol digit modality test (SDMT), the Rey-Osterrieth Complex Figure Test Copy, the FAS Verbal Fluency Test and the Rey Auditory Verbal learning Test. The long follow-up time between the neuropsychological tests should reduce the risk of learning effects.  Cognitive impairment was defined as an abnormally low performance in any of the four tests. Matched controls were included at the latest follow-up. During the last 8.5 years of the study, brain MRI was used to analyze normalized volumetrics of three tissue compartments (grey and white matter, lesions) and certain strategic areas (hippocampus, thalamus and hypothalamus).

The study showed that cognitive decline develops in a predominantly linear fashion on a group level in MS. SDMT was most frequently abnormal and the largest cognitive decline over the disease duration was found for Rey-Osterreith Complex Figure Test. There was a partial correlation between EDSS and the cognitive index, but individual patients may show a predominantly physical or cognitive disability. For MRI measurements, cognitively impaired patients had lower white matter fraction, lower corpus callosum faction, lower thalamus fraction and higher lesion fraction, while there was no difference in hippocampal fraction. Multiple linear regression analysis showed that cognitive disabilities are mainly associated with lesion accumulation and corpus callosum atrophy. These results together with the finding that some of the neuropsychological tests reflecting more wide spread functions were more affected could support the the hypothesis of a disconnection mechanism for cognitive decline in MS.

Ouellette R, Bergendal Å, Shams S, Martola J, Mainero C, Kristoffersen Wiberg M, Fredrikson S, Granberg T. Lesion accumulation is predictive of long-term cognitive decline in multiple sclerosis. Mult Scler Relat Disord. 2018 Apr;21:110-116