Research: Grey Matter Disease and Cognition

Epub: Nocentini et al.  Exploration of the relationships between regional grey matter atrophy and cognition in multiple sclerosis. Brain Imaging Behav. 2012 May 15.

Background: Cognitive impairment may result in significant disability in MSers. Previous MRI studies on cognition in MS were mainly based on measures of gross brain involvement. This study, using voxel-based morphometry (VBM), a technique designed to look a fine detail, aims to investigate associations between the regional distribution of grey matter (GM) damage and cognitive performance in MSers. 

Methods: 18 MSers underwent an extensive neuropsychological battery and MRI, including T2-weighted scans and T1-weighted volumes. A group of 18 healthy individuals were also investigated by MRI and served as controls for the VBM. A cross-sectional analysis was first performed, to assess the pattern of regional GM atrophy in MSers. Then, the impact of regional GM damage on patients' neuropsychological performance was investigated by multiple regression analyses in the MSer group. Correlations between global indexes of brain damage and neuropsychological measures were also assessed for comparison with previous literature. 

Results: The comparison between MSers and healthy controls revealed a widespread pattern of regional GM atrophy (loss). Consistent with previous studies, associations were found between neuropsychological scores, and global brain atrophy and T2-lesion volumes (MS lesion volume). Critically, significant associations were found between scores on the Symbol Digit Modalities test and Long Delay Cued Recall on the California Verbal Learning Test (these are all tests of cognition), and regional GM volumes in well localized areas of the prefrontal, parietal, temporal, and insular cortex (specific areas of the brain). 

Conclusions: This study confirms that global assessments of brain damage correlate with measures of cognitive impairment in MS. Interestingly, VBM contributes to clarify those brain regions that more likely determine the cognitive deficits observed in MSers. These findings clarify the pathophysiology of cognitive impairment in MS, and propose measures which could be considered for longitudinal monitoring of patients.

"This study confirms that MS is a serious illness and results in damage to the gray matter of the brain with it shrinking in specific areas. These brain areas that have been shown to shrink are linked to important cognitive functions. Therefore it is not surprising that the brain damage in MSers correlated with deficits on cognitive testing."

"How early does this brain damage occur in MS? Very early; at the very first clinical event or CIS there is evidence of gray matter damage. This then accumulates over time. There is evidence that effective DMTs delays or slows down this damage. This is why I am a proponent of treating early and actively; I think it is important to try and suppress all disease activity. Whether we can do this or not is currently unknown. The strategy also implies that if MSers understand why we need to treat early and actively may choose more risky treatments with greater efficacy early on. Unfortunately, access to these more risky treatments is not universal and are limited by factors such as cost and regulatory issues, for example in  the UK NICE limits access of certain drugs to MSers with very active or so called highly-active disease."

CoI: multiple

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