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MRI techniques and cognitive impairment in the early phase of relapsing-remitting multiple sclerosis
R Zivadinov1, R De Masi, D Nasuelli
1Neurological Clinic, Cattinara Hospital, Strada di Fiume, 447-34149 Trieste, Italy. zivadinov@hotmail.com
Abstract:
Correlation studies between various conventional and non-conventional MRI parameters and cognitive impairment in the early stages of multiple sclerosis (MS) are lacking, although it is known that a number of patients with early MS have mild cognitive impairment. Our aim was to explore whether this cognitive impairment is dependent on the extent and severity of the burden of disease, diffuse microscopic brain damage or both. We studied 63 patients with clinically definite relapsing-remitting (RR) MS, duration of disease 1-10 years and Expanded disability status scale scores < or = 5.0. Mean age was 35.4 years, mean duration of disease 5.8 years and median EDSS score 1.5. Neuropsychological performance, psychological function, neurological impairment and disability were assessed. The patients also underwent MRI, including magnetisation-transfer (MT) studies. We quantified the lesion load on T2- and T1-weighted images, the magnetisation transfer ratio (MTR) of normal-appearing brain tissue (NABT) and the brain parenchymal fraction (BPF). No significant difference was found between lesion loads in patients with and without cognitive impairment. In 15 patients (23.8%) with overall cognitive impairment, median BPF and average NABT MTR were significantly lower than those in patients without cognitive impairment (0.868 vs 0.892, P = 0.02 and 28.3 vs 29.7 P = 0.046, respectively). Multiple regression analysis models demonstrated that the only variables independently correlated with cognitive impairment were: BPF (R = 0.89, P = 0.001) and average NABT MTR (R = 0.76, P = 0.012). Our findings support the hypothesis that, cognitive decline in patients with MS, a low disability score and short duration of disease is directly associated with the extent and severity of diffuse brain damage. The loss of brain parenchyma did not correlate with the severity of microscopic damage in the NABT, indicating that the two processes could be distinct in the early stages of the disease.
Insights
Early multiple sclerosis (MS) cognitive decline is linked to diffuse brain damage, not just lesion load. Brain parenchymal fraction and normal-appearing brain tissue magnetisation transfer ratio are key indicators.
Area of Science:
- Neuroimaging
- Neurology
- Cognitive Science
Background:
- Cognitive impairment is common in early multiple sclerosis (MS), but its relationship with disease burden and brain damage is not fully understood.
- Existing research lacks comprehensive correlation studies between various MRI parameters and cognitive deficits in early MS.
- Investigating these correlations is crucial for understanding the pathophysiology of cognitive decline in MS.
Purpose of the Study:
- To explore the association between cognitive impairment and disease burden, diffuse brain damage, or both in early relapsing-remitting MS.
- To identify specific MRI parameters that correlate with cognitive impairment in early MS patients.
- To differentiate the roles of macroscopic (lesion load) and microscopic (normal-appearing brain tissue) damage in cognitive decline.
Main Methods:
- Studied 63 patients with early relapsing-remitting MS (disease duration 1-10 years, EDSS ≤ 5.0).
- Assessed neuropsychological performance, psychological function, neurological impairment, and disability.
- Utilized MRI, including magnetisation-transfer (MT) imaging, to quantify lesion load, brain parenchymal fraction (BPF), and magnetisation transfer ratio (MTR) of normal-appearing brain tissue (NABT).
Main Results:
- No significant difference in lesion load was found between cognitively impaired and unimpaired patients.
- Patients with cognitive impairment showed significantly lower BPF and average NABT MTR compared to those without.
- Multiple regression analysis revealed BPF and average NABT MTR as independent predictors of cognitive impairment.
Conclusions:
- Cognitive decline in early MS is associated with the extent of diffuse brain damage, specifically reduced BPF and impaired NABT MTR.
- Macroscopic lesion load does not appear to be the primary driver of cognitive impairment in this early MS cohort.
- These findings suggest distinct pathological processes contributing to brain atrophy and white matter integrity loss in early MS, both impacting cognition.