Cognitive Impairment In Multiple Sclerosis Patients Research Articles

Cognitive impairment in multiple sclerosis is associated to different patterns of gray matter atrophy according to clinical phenotype

To investigate whether cognitive impairment in multiple sclerosis (MS) patients is associated to different patterns of gray matter (GM) atrophy and T2-visible lesion distribution according to the clinical phenotype. Twenty-two relapsing remitting (RR), 29 secondary progressive (SP), and 22 primary progressive (PP) MS patients, and 39 healthy controls underwent high-field structural magnetic resonance imaging and an extensive neuropsychological battery. Voxel-wise distribution of GM damage and T2-lesions was compared between cognitively impaired (CI) and cognitively preserved (CP) patients according to their clinical phenotype. Thirty-nine MS patients were CI. In all MS groups, regional GM loss was correlated with cognitive impairment. Different patterns of regional distribution of GM atrophy and T2-visible lesions were found between CI vs. CP MS patients, according to their clinical phenotype. No areas were significantly more atrophied in CI SPMS vs. CI RRMS patients. Conversely, compared with CI PPMS, CI SPMS patients had a significant GM loss in several regions of the fronto-temporal lobes, the left hypothalamus and thalami. While in RRMS and SPMS patients there was a correspondence between presence of T2 visible lesions and GM atrophy in several areas, this was not the case in PPMS patients. Distinct patterns of regional distribution of GM damage and T2-visible lesions are associated with cognitive impairment in MS patients with different clinical phenotypes. The correspondence between lesion formation and GM atrophy distribution varies in the different forms of MS.

Les troubles cognitifs

Cognitive impairment is common in multiple sclerosis (MS), occurring at all stages of the disease, even at the earliest, and can be a major source of disability, social impairment, and impoverished quality of life. Cognitive dysfunction is mainly focused on working memory, conceptual reasoning, verbal fluency, speed of information processing, attention and executive function. Measures of information-processing speed appear to be the most robust and sensitive markers of cognitive impairment in MS patients. Cognitive testing in MS patients is complex and cognitive screening tests are time- and cost-saving test instruments. A comprehensive and sensitive cognitive test procedure should be administered to detect cognitive dysfunction, and recent studies demonstrate that single, predominantly speed-related cognitive tests may be superior to extensive and time-consuming test batteries in screening cognitive decline. Additional clinical factors, including disease course, fatigue, and affective disturbance, can impact the degree of MS-related cognitive impairment. Despite weak correlation with disease duration and physical disability status, the degree of cognitive impairment in MS has been related to the extent of topographically specific neuronal tissue damage and loss. Numerous studies have applied conventional and quantitative magnetic resonance imaging (MRI) techniques to correlate the profile and degree of cognitive impairment with various MRI-detectable abnormalities. The burden of MRI-visible lesions does not fully account for the degree of MS-related cognitive impairment. Nonconventional MRI findings suggest the extent of subtle tissue damage in normal-appearing white and grey matter to correlate best with the severity of cognitive impairment in MS patients. Structural MRI approaches have recently been extended by functional MRI studies scrutinizing the brain's ability for adaptive functional reorganization in the presence of widespread tissue damage. Cognitive impairment in MS seems to be not simply the result of tissue destruction, but also a balance between tissue destruction, tissue repair, and adaptive functional reorganization. These findings highlight the need to screen for cognitive deficits in MS patients to conduct potential cognitive rehabilitation intervention.

APOE and risk of cognitive impairment in multiple sclerosis.

The APOE gene polymorphism and the -491 A/T polymorphism in its regulatory region have been associated with an increased risk for developing Alzheimer's disease. We examined these polymorphisms in multiple sclerosis (MS) patients, to determine if a genetic predisposition may explain the risk for developing cognitive decline in MS. Eighty-nine relapsing-remitting and secondary progressive MS patients underwent to a full neuropsychological battery as well as to determination of APOE and -491 A/T polymorphisms. Genetic analysis was also performed in 107 population controls. The APOE polymorphism was not associated with the risk of cognitive impairment in MS patients. The AA genotype of the -491 A/T polymorphism in the APOE regulatory region was more frequent in cognitively impaired than in cognitively preserved MS subjects. The AA homozygous state of the -491 A/T polymorphism of the APOE regulatory region is associated with cognitive impairment in patients with MS.

Cognitive impairment in patients with multiple sclerosis using the Brief Repeatable Battery-Neuropsychology test

Aims To assess the cognitive impairment of multiple sclerosis (MS) patients using the Brief Repeatable Battery-Neuropsychology (BRB-N) test. Methods The performance of 59 patients with MS in the BRB-N test was assessed and compared with 152 matched healthy controls (HC). Results In most tests, MS patients performed worse than controls. Age and educational level strongly influenced the performance of the subjects. The Symbol Digit Modality Test (SDMT) best correlated with the other individual tests and contributed most to the general BRB-N factor. Furthermore, a correlation between physical disability and performance in some BRB-N tests was observed. Indeed, patients with progressive MS and greater physical disability performed worse in some tests than less disabled patients with relapsing MS. By creating a global BRB-N Z score, we found that patients generally performed 0.7 standard deviation (SD) below the level of controls. We obtained cut-off values stratified by age and education to determinate cognitive impairment in MS patients. Conclusions Our data show that cognitive impairment is prevalent amongst MS patients, and that a single cognitive measurement might be useful for monitoring patients during the progression of this illness.

Cognitive dysfunction in patients with relapsing-remitting multiple sclerosis

Cognitive dysfunction is considered one of the clinical markers of multiple sclerosis (MS). However, in the literature there are inconsistent reports on the prevalence of cognitive dysfunction, and separate data for the relapsing-remitting (RR) type of the disease are not always presented. In this study, we submitted 461 RRMS patients to a battery of neuropsychological tests to investigate their impairment in various cognitive domains. As a consequence of the exclusion criteria, the sample is not fully representative of the entire population of RRMS patients. In this selected sample, when only the eight scores of a core battery (Mental Deterioration Battery) were considered (with respective cutoffs), it emerged that 31% of the patients were affected by some degree of cognitive deficit. In particular, 15% had mild, 11.2% moderate and 4.8% had severe impairment. Information processing speed was the most frequently impaired area, followed by memory. When two other tests (SDMT and MCST) were added and cognitive domains were considered, it emerged that 39.3% of the patients were impaired in two or more domains. When four subgroups were obtained by means of cluster analysis and then compared, it emerged that information processing speed and memory deficits differentiated the still cognitively unimpaired from the mildly impaired MS patients. Significant associations were found between cognitive and clinical characteristics. However, due to the large sample size, clinically irrelevant relationships may also have emerged. Even with the limitations imposed by the sample selection and the possible underestimation of the prevalence and severity of cognitive dysfunction, these results seem to provide further evidence that information processing speed deficit may be an early and important marker of cognitive impairment in MS patients.

La BCcogSEP : une batterie courte d’évaluation des fonctions cognitives destinées aux patients souffrant de sclérose en plaques

In French language, there is no standardized procedure to assess cognitive function in patients with multiple sclerosis (MS). Such an assessment is however very useful to determine the consequences of the disease on cognitive function, to evaluate the disease progression and the consequences of usual treatments on cognition. This study aimed to develop and validate a French language battery based on "the Brief Repeatable Battery of Neuropsychological tests for Multiple Sclerosis" (BRB-N) often used in other countries. In an initial phase, the battery was composed of the French version of the 5 BRB-N tests to which were added 4 tests assessing immediate and working memory as well as executive function. 52 healthy control subjects (20-50 years) participated in the study. A principal component analysis (PCA) of their data examined the contribution of each test into the battery. 93 other healthy subjects participated in a second phase where analyses of variance were carried out to investigate the effect of the main demographical variables. Finally, the performance of two patient groups (20 with a EDSS score<or=3 et 31 with a EDSS score>3) was compared to the healthy controls in order to investigate the ability of our battery to detect cognitive impairment in MS patients. The PCA showed that each test, except one, had a specific contribution to the battery. The final battery (BCcogSEP) was thus comprised of 8 tests. MANOVA and ANOVA showed significant effects of age, sex and educational level on performance. In consequence, a procedure allowing to take into account these factors was developed. The battery was able to detect cognitive impairment in MS patients, even when the disease is not severe. In this case, deficits were observed in tests assessing executive function, information processing speed, immediate and working memory. This short battery with reliable psychometric qualities allows the interpretation of a MS patient's performance considering his/her demographical characteristics and is able to detect cognitive abnormalities even in case of mild physical handicap.

Clinical and MRI assessment of brain damage in MS.

Cognitive impairment in multiple sclerosis (MS), generally in the form of the so-called subcortical dementia, results predominantly by the disruption of communication among cortical and subcortical areas, consequent to white matter damage. Studies with conventional magnetic resonance imaging (MRI) demonstrated that cognitive impairment in MS patients is related to lesion burden, although the strength of this correlation is weak. This can be partially explained by the poor pathological specificity of conventional MRI techniques and by damage in the normal-appearing white matter (NAWM). This interpretation is supported by studies using non-conventional MRI techniques, more specific to the heterogeneous substrates of MS pathology, such as the assessment of hypointense lesion load on T1-weighted scans and the measurement of the magnetization transfer ratio (MTR) of whole brain, MS lesions and NAWM. Other factors, such as the site of MS lesions and the presence of active inflammation, also seem to play an important role.

Assessment of the damage of the cerebral hemispheres in MS using neuroimaging techniques.

The pattern of mental dysfunction in multiple sclerosis (MS) is characteristic of the so-called subcortical dementia. Cognitive dysfunction results predominantly by the disruption of communication among cortical and subcortical areas, as a consequence of the white matter damage. As expected, studies with conventional magnetic resonance imaging (MRI) demonstrated that cognitive impairment in MS patients is related to the lesion burden, although the strength of this correlation is weak. This can be partially explained by the poor pathological specificity of conventional MRI techniques and by the invisible damage in the normal-appearing white matter (NAWM). Recent studies using non-conventional MRI techniques with a higher specificity for the heterogeneous substrates of MS pathology, such as the assessment of hypointense lesion load on T1-weighted scans and the measurement of the magnetization transfer ratio (MTR) of whole brain, MS lesions and NAWM, support this interpretation. Other factors, such as the site of MS lesions and the presence of active inflammation, also seem to play an important role.