Exploration of the relationships between regional grey matter atrophy and cognition in multiple sclerosis. (original) (raw)
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In a multicenter setting, we applied voxel-based methods to different structural MR imaging modalities to define the relative contributions of focal lesions, normal-appearing white matter (NAWM) and gray matter (GM) damage and their regional distribution to cognitive deficits as well as impairment of specific cognitive domains in multiple sclerosis (MS) patients. Approval of the institutional review boards was obtained, together with written informed consent from all participants. Standardized neuropsychological assessment and conventional, diffusion tensor and volumetric brain MRI sequences were collected from 61 relapsing-remitting MS patients and 61 healthy controls (HC) from seven centers. Patients with ≥2 abnormal tests were considered cognitively impaired (CI). The distribution of focal lesions, GM and WM atrophy and microstructural WM damage were assessed using voxel-wise approaches. A random forest analysis identified the best imaging predictors of global cognitive impairment and deficits of specific cognitive domains. Twenty-three (38%) MS patients were CI. Compared to cognitively preserved (CP), CI MS patients had GM atrophy of the left thalamus, right hippocampus and parietal regions. They also showed atrophy of several WM tracts, mainly located in posterior brain regions and widespread WM diffusivity abnormalities. WM diffusivity abnormalities in cognitive-relevant WM tracts followed by atrophy of cognitive-relevant GM regions explained global cognitive impairment. Variable patterns of NAWM and GM damage were associated with deficits in selected cognitive domains. Structural, multiparametric, voxel-wise MRI approaches are feasible in a multicenter setting. The combination of different images modalities is needed to assess and monitor cognitive impairment in MS.
Structural MRI correlates of cognitive impairment in patients with multiple sclerosis
Human Brain Mapping, 2016
In a multicenter setting, we applied voxel-based methods to different structural MR imaging modalities to define the relative contributions of focal lesions, normal-appearing white matter (NAWM) and gray matter (GM) damage and their regional distribution to cognitive deficits as well as impairment of specific cognitive domains in multiple sclerosis (MS) patients. Approval of the institutional review boards was obtained, together with written informed consent from all participants. Standardized neuropsychological assessment and conventional, diffusion tensor and volumetric brain MRI sequences were collected from 61 relapsing-remitting MS patients and 61 healthy controls (HC) from seven centers. Patients with ≥2 abnormal tests were considered cognitively impaired (CI). The distribution of focal lesions, GM and WM atrophy and microstructural WM damage were assessed using voxel-wise approaches. A random forest analysis identified the best imaging predictors of global cognitive impairment and deficits of specific cognitive domains. Twenty-three (38%) MS patients were CI. Compared to cognitively preserved (CP), CI MS patients had GM atrophy of the left thalamus, right hippocampus and parietal regions. They also showed atrophy of several WM tracts, mainly located in posterior brain regions and widespread WM diffusivity abnormalities. WM diffusivity abnormalities in cognitive-relevant WM tracts followed by atrophy of cognitive-relevant GM regions explained global cognitive impairment. Variable patterns of NAWM and GM damage were associated with deficits in selected cognitive domains. Structural, multiparametric, voxel-wise MRI approaches are feasible in a multicenter setting. The combination of different images modalities is needed to assess and monitor cognitive impairment in MS.
The contribution of MRI in assessing cognitive impairment in multiple sclerosis
Neurology, 2010
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.
Relation between MR abnormalities and patterns of cognitive impairment in multiple sclerosis
Neurology, 1998
This study correlated the extent of abnormalities detected by different magnetic resonance imaging (MRI) techniques [proton density (PD)-weighted, T1-weighted, and magnetization transfer imaging (MTI)] with the overall cognitive, frontal lobe, and memory impairments in patients with MS. Patients: There were 30 clinically definite MS patients, with different disease courses. Exclusion criteria: psychoactivelsteroid treatments, mood disorders, acute relapse phase. Main Outcome Measures: Neuropsychological test results. Total (TLL) and frontal (FLL) lesion loads assessed from PD-weighted, T1-weighted (22 patients), and MTI (22 patients) MRI scans. Average lesion MT ratios (MTR) and analysis of the MTR histograms from brain tissue axial slabs on MTI scans. Results: Patients with frontal lobe deficits (n = 15) or memory impairment (n = 17) had a higher TLL on PD scans (p = 0.04 and p = 0.01, respectively). Patients with frontal lobe deficits had higher FLL on PD scans (p = 0.01) and TLL on MTI (p = 0.03) scans. No significant relationships between the extent of T1-weighted lesion loads and the presence of any neuropsychological impairment. Mean MTR of both MS lesions and whole brain tissue was lower in patients with frontal lobe impairment (p = 0.04). MRI lesion loads correlated significantly with some neuropsychological test scores. Conclusions: Lesion loads on PD-weighted MRI and MTI-derived measures are associated with cognitive decline in MS patients. Overall macroscopic and microscopic brain damage is more important than the corresponding regional brain disease in determining deficits of selective cognitive domains.
American Journal of Neuroradiology, 2016
BACKGROUND AND PURPOSE: The structural MR imaging correlates of cognitive impairment in multiple sclerosis are still debated. This study assessed lesional and atrophy measures of white matter and gray matter involvement in patients with MS acquired in 7 European sites to identify the MR imaging variables most closely associated with cognitive dysfunction. MATERIALS AND METHODS: Brain dual-echo, 3D T1-weighted, and double inversion recovery scans were acquired at 3T from 62 patients with relapsing-remitting MS and 65 controls. Patients with at least 2 neuropsychological tests with abnormal findings were considered cognitively impaired. Focal WM and cortical lesions were identified, and volumetric measures from WM, cortical GM, the hippocampus, and deep GM nuclei were obtained. Age-and site-adjusted models were used to compare lesion and volumetric MR imaging variables between patients with MS who were cognitively impaired and cognitively preserved. A multivariate analysis identified MR imaging variables associated with cognitive scores and disability. RESULTS: Twenty-three patients (38%) were cognitively impaired. Compared with those with who were cognitively preserved, patients with MS with cognitive impairment had higher T2 and T1 lesion volumes and a trend toward a higher number of cortical lesions. Significant brain, cortical GM, hippocampal, deep GM nuclei, and WM atrophy was found in patients with MS with cognitive impairment versus those who were cognitively preserved. Hippocampal and deep GM nuclei atrophy were the best predictors of cognitive impairment, while WM atrophy was the best predictor of disability. CONCLUSIONS: Hippocampal and deep GM nuclei atrophy are key factors associated with cognitive impairment in MS. These MR imaging measures could be applied in a multicenter context, with cognition as clinical outcome. ABBREVIATIONS: CI ϭ cognitively impaired; CL ϭ cortical lesion; CP ϭ cognitively preserved; DIR ϭ double inversion recovery; EDSS ϭ Expanded Disability Status Scale; HC ϭ healthy controls; LV ϭ lesion volumes; WCST ϭ Wisconsin Card Sorting Test C ognitive impairment is a frequent finding in patients with multiple sclerosis, with 40%-70% of patients showing cognitive deficits. 1 The most affected domains are attention, information-processing speed, executive functions, and memory and visuospatial abilities. 1 Given its dramatic effect on the activities of patients' daily lives, there is a critical need to define the pathophysiologic mechanisms of cognitive impairment in MS, to develop markers for its monitoring, and to identify valid therapeutic strategies. Many studies tried to characterize the structural MR imaging correlates of cognitive impairment in patients with MS. T2 and T1 lesion volumes were found to be generally higher in patients with
Clinical and imaging assessment of cognitive dysfunction in multiple sclerosis
The Lancet Neurology, 2015
In patients with multiple sclerosis (MS), grey matter damage is widespread and might underlie many of the clinical symptoms, especially cognitive impairment. This relation between grey matter damage and cognitive impairment has been lent support by fi ndings from clinical and MRI studies. However, many aspects of cognitive impairment in patients with MS still need to be characterised. Standardised neuropsychological tests that are easy to administer and sensitive to disease-related abnormalities are needed to gain a better understanding of the factors aff ecting cognitive performance in patients with MS than exists at present. Imaging measures of the grey matter are necessary, but not suffi cient to fully characterise cognitive decline in MS. Imaging measures of both lesioned and normal-appearing white matter lend support to the hypothesis of the existence of an underlying disconnection syndrome that causes clinical symptoms to trigger. Findings on cortical reorganisation support the contribution of brain plasticity and cognitive reserve in limiting cognitive defi cits. The development of clinical and imaging biomarkers that can monitor disease development and treatment response is crucial to allow early identifi cation of patients with MS who are at risk of cognitive impairment.
A multiparametric MRI study of frontal lobe dementia in multiple sclerosis
Journal of the Neurological Sciences, 1999
Previous studies achieved conflicting results when correlating magnetic resonance imaging (MRI) abnormalities and cognitive impairment in multiple sclerosis (MS) patients. Recently, the estimation of MS lesion load on T1-weighted images and the analysis of magnetization transfer ratio (MTR) histograms, increased the degree of the correlation between physical disability and MRI findings in MS. We assessed the relationship of conventional and non-conventional MRI-derived measures with frontal lobe dementia in MS. Dual echo, T1-weighted and MT MRI scans of the brain were obtained in 11 MS patients with and in 11 without frontal lobe dementia, matched for age, sex, education and disability. Total (TLL) and frontal (FLL) lesion loads were assessed from T2-and T1-weighted scans. MTR histogram analysis was performed for the whole brain, the frontal lobe and the cerebellum. Median TLL and FLL were significantly higher in cognitively impaired patients on both T2-and T1-weighted scans. The MRI measure that better discriminated the two groups of patients was T1-weighted TLL (median values were 19.1 ml for demented and 1.9 ml for non-demented patients, P50.006). Average MTR, peak height and location of overall brain and frontal lobe histograms were significantly lower for cognitively impaired than for cognitively intact patients (P values ranged from 0.0001 to 0.001). Cerebellar MTR histogram metrics did not significantly differ in patients with and without cognitive decline. The presence of cognitive decline in MS is associated with the extent and pathological severity of brain MRI abnormalities.
Cognitive functions in multiple sclerosis: impact of gray matter integrity
Multiple Sclerosis Journal, 2013
Objectives: Our aim was to investigate the impact of gray matter (GM) integrity on cognitive performance in multiple sclerosis (MS), and its relationship with white matter (WM) integrity and presence of lesions. Methods: Sixty-seven patients with MS and 26 healthy controls underwent voxel-based analysis of diffusion tensor images (DTI) in GM and tract-based spatial statistics (TBSS) from WM to identify the regional correlations between cognitive functions and integrity. Lesion probability mapping (LPM) was generated for correlation analysis with cognition. Multiple linear regression analyses were used to identify the imaging measures associated with cognitive scores. Results: Compared with controls, patients showed abnormal DTI indices in several GM regions and in most WM tracts. Impairment in DTI indices in specific GM regions was associated with worse performance of distinct cognitive functions. Those regions showed anatomical correspondence with cognitively relevant tracts in TBSS and LPM. The combination of regional GM and WM DTI and lesion volume accounted for 36-51% of the variance of memory and attention scores. Regional GM DTI explained less than 5% of that variance. Conclusion: GM and WM integrity of specific networks influences cognitive performance in MS. However, GM damage assessed by DTI only adds a small increment to the explained variance by WM in predicting cognitive functioning.
Regional MRI lesion burden and cognitive function in MS: A longitudinal study
Objective: To investigate the relationship between magnetic resonance imaging (MRI) regional lesion burden and cognitive performance in multiple sclerosis (MS) over a four year follow-up period. Design: Twenty-eight patients with MS underwent MRI and the Brief Repeatable Battery of Neuropsychological Tests in MS [1] (BRB) at baseline, 1 year and 4 year follow-up. An automated 3-D lesion detection method was used to identify MS lesions within anatomic regions on proton density/T2-weighted images. The relationship between MRI regional lesion volumes and BRB tests was examined using regression analyses. Results: At all time points, frontal lesion volume represented the greatest proportion of total lesion volume, and the percentage of white matter classified as lesion was also highest in frontal and parietal regions. On neuropsychological testing, when compared to age and education matched control subjects, MS patients showed significant impairments on tests of sustained attention, proc...