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Functional and structural brain MRI changes associated with cognitive worsening in multiple sclerosis: a 3-year
Matteo Azzimonti1,2, Paolo Preziosa1,2,3, Elisabetta Pagani1
1Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.
Background:
Heterogeneous processes may contribute to cognitive impairment in multiple sclerosis (MS).
Objective:
To apply a longitudinal multiparametric MRI approach to identify mechanisms associated with cognitive worsening in MS patients.
Methods:
3 T brain functional and structural MRI scans were acquired at baseline and after a median follow-up of 3.4 years in 35 MS patients and 22 healthy controls (HC). Associations between cognitive worsening (reliable change index score < - 1.25 at the Rao's battery) and longitudinal changes in regional T2-hyperintense white matter (WM) lesions, diffusion tensor microstructural WM damage, gray matter (GM) atrophy and resting state (RS) functional connectivity (FC) were explored.
Results:
At follow-up, HC showed no clusters of significant microstructural WM damage progression, GM atrophy or changes in RS FC. At follow-up, 10 MS patients (29%) showed cognitive worsening. Compared to cognitively stable, cognitively worsened MS patients showed more severe GM atrophy of the right anterior cingulate cortex and bilateral supplementary motor area (p < 0.001). Cognitively worsened vs cognitively stable MS patients showed also decreased RS FC in the right hippocampus of the right working memory network and in the right insula of the default mode network. Increased RS FC in the left insula of the executive control network was found in the opposite comparison (p < 0.001). No significant regional accumulation of focal WM lesions nor microstructural WM abnormalities occurred in both patients' groups.
Conclusions:
GM atrophy progression in cognitively relevant brain regions combined with functional impoverishment in networks involved in cognitive functions may represent the substrates underlying cognitive worsening in MS.
Insights
Cognitive worsening in multiple sclerosis (MS) is linked to gray matter atrophy and reduced functional connectivity in key brain networks. These changes in gray matter and brain networks are the primary drivers of cognitive decline in MS patients.
Area of Science:
- Neuroimaging
- Neurology
- Cognitive Science
Background:
- Multiple Sclerosis (MS) is associated with heterogeneous processes that can lead to cognitive impairment.
- Understanding the underlying mechanisms of cognitive decline in MS is crucial for developing effective interventions.
Purpose of the Study:
- To investigate the longitudinal changes in brain structure and function associated with cognitive worsening in MS patients.
- To identify specific MRI-based biomarkers predictive of cognitive decline in MS.
Main Methods:
- A longitudinal multiparametric MRI approach was used, including functional and structural scans.
- 35 MS patients and 22 healthy controls (HC) underwent MRI at baseline and after a median follow-up of 3.4 years.
- Cognitive function was assessed using Rao's battery, and cognitive worsening was defined by a reliable change index score < -1.25.
Main Results:
- At follow-up, 29% of MS patients showed cognitive worsening.
- Cognitively worsened MS patients exhibited more severe gray matter (GM) atrophy in the anterior cingulate cortex and supplementary motor area compared to stable patients.
- Decreased resting-state functional connectivity (RS FC) was observed in the hippocampus (working memory network) and insula (default mode network) in cognitively worsened MS patients.
Conclusions:
- Gray matter atrophy progression in critical cognitive regions is a key substrate for cognitive worsening in MS.
- Functional impoverishment in brain networks involved in cognitive functions contributes significantly to cognitive decline in MS.
- Longitudinal multiparametric MRI can identify mechanisms underlying cognitive worsening in MS.
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