The contribution of MRI in assessing cognitive impairment in multiple sclerosis

Abstract

Cognitive impairment affects a large proportion of patients with multiple sclerosis (MS) and has a profound impact on their daily-life activities. Improving the knowledge of the pathophysiology of cognitive impairment in MS and of the mechanisms responsible for its evolution over time might contribute to development of better outcome measures and targets for innovative treatment strategies. Due to their ability to detect MS-related abnormalities, MRI techniques are a valuable tool to achieve these goals. Following an updated overview of the assessment methods and profile of cognitive impairment in patients with MS, this review provides a state-of-the-art summary of the main results obtained from the application of conventional and modern magnetic resonancebased techniques to quantify MS-related damage, in terms of macroscopic lesions, as well as involvement of the normal-appearing white matter and gray matter and their association with cognitive impairment. The possible role of brain cortical reorganization in limiting the clinical consequences of disease-related damage is also discussed. Finally, the utility of the previous techniques to monitor the progression of cognitive deficits over time and the efficacy of possible therapeutic strategies is considered. Neurology Cognitive impairment affects a large proportion of patients with multiple sclerosis (MS), with a prevalence rate ranging from 40% to 70%.1,2 Although cognitive deficits have been observed from the early stages of the disease, they are more frequent and pronounced in chronic progressive MS and tend to worsen over time. Cognitive capacity is critical for a range of activities such as work, driving, and adherence to medication regimen, but in diseases such as MS, where physical disability is prominent, cognitive impairment is sometimes overlooked or even disregarded. The definition of the mechanisms underlying its development and the identification of markers useful to monitor its progression might contribute to drive future pharmacologic and rehabilitative strategies.MRI is the most used paraclinical tool to investigate in vivo the pathobiology of MS and to monitor disease evolution.3 After providing a clinical background of the main cognitive deficits encountered in patients with MS, and of the most suitable tests for their assessment, this review summarizes the contribution provided by conventional and quantitative magnetic resonance

Differential diagnosis, discerning depression from cognition

“…Moreover, brain regions involved in dysfunctional emotion regulation and mood disorders greatly overlap with key regions affected in MS-related cognitive impairment. 11 With this background, it is straightforward to wonder whether there is a relationship between depression and cognitive functioning in MS and whether there is a specific profile of depression-related cognitive impairment.…”

Functional MRI in investigating cognitive impairment in multiple sclerosis

“…4 The application of functional MRI (fMRI) has led to the exploration of the role of brain plasticity and functional reorganization in contrasting cognitive dysfunction in MS.…”

Contribution of cortical lesion subtypes at 7T MRI to physical and cognitive performance in MS

“…Conventional and quantitative MRI have identified potential biomarkers and better defined the pathophysiology of cognitive dysfunction in MS. 4 To date, global rather than regional metrics of cortical atrophy and cortical lesion (CL) volume using double inversion recovery (DIR) sequences at 3 tesla (3T) better account for the variance seen in cognitive performance in MS-supplanting conventional white matter (WM) MRI metrics. 5,6 These findings are not entirely unexpected because MS neuropathology has highlighted the cortex as a major location of demyelination.…”

“…Moreover, we were able to determine these correlations with a small group of patients with MS. Because cognitive impairment in MS increases as the disease ensues, with or without similar levels of physical disability progression, further longitudinal observation of this cohort should allow us to identify global and regional mechanisms of injury responsible for both physical and cognitive disease progression. 4,39 …”