Cognitive Dysfunction in MS: Bridging the Gap Between Neurocognitive Deficits, Neuropsychological Batteries and MRI

Erica Grazioli; Ann E Yeh; Ralph HB Benedict; Joy Parrish; Bianca Weinstock-Guttman

Disclosures

Future Neurology. 2008;3(1):49-59. 

In This Article

Abstract and Introduction

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the CNS. Its sequelae include both physical and cognitive disability. Advances in neuropsychological testing and screening have led to increased recognition of cognitive impairment in MS; more than half of MS patients have been found to have some degree of cognitive impairment. Strong correlations have been found between neuropsychological testing, brain atrophy and other brain imaging techniques. These tools can aid in the comprehensive evaluation of MS patients. Genetic markers, such as ApoE and brain-derived neurotrophic factor polymorphisms, may also correlate with cognitive impairment in MS. This review details advances in recognizing and predicting cognitive dysfunction in MS. Increased understanding and better evaluation and monitoring of cognitive status in MS may improve the sensitivity of studies designed to test new disease-modifying therapies and interventions for cognitive impairment.

Multiple sclerosis (MS) is considered the most common chronic disease affecting the CNS in young adults. The natural history of the disease is best characterized by progressive physical decline, with 50% of patients requiring the use of an assistive device after 15 years.[1] Although the devastating effect of the disease on physical status is well recognized and easy to detect, its impact on cognitive function is less appreciated, even though it was described almost 100 years ago by Jean-Martin Charcot.[2] Charcot described patients with 'multilocular sclerosis' who have "a marked enfeeblement of the memory, conceptions being formed slowly and the intellectual and emotional faculties being blunted in their totality". Cognitive dysfunction in MS is often difficult to detect on routine clinical/neurological examination because patients' language skills and intellectual function are often preserved.[3] However, using sensitive neuropsychological (NP) testing, multiple cross-sectional studies have demonstrated that up to 60% of MS patients may have certain cognitive impairments.[3,4] These impairments can vary in intensity, affecting the circumscribed domains of memory, attention, information processing speed and visuospatial abilities. Identifying and quantifying cognitive impairments in this group of usually young or middle-aged adults is of central importance because of its potential impact on employment, quality of life, care givers, family and society.[4,5]

During the last 15 years, significant progress has been achieved in the complex process of detection, quantification and monitoring of the cognitive performance in MS patients. This was made possible by creating and validating sensitive and reliable NP tests that focus on the areas of impairment noted above. Collections of tests or 'batteries' can be repeatedly administered to identify and monitor cognitive status and patient response to specific therapeutic interventions. These NP batteries are also highly correlated with brain MRI measures, which provide information not only on macroscopic brain damage, such as T2 total lesion volume and gray and white matter brain volume, but also on microscopic brain injury measured with more sophisticated techniques, such as diffusion-weighted imaging (DWI) or magnetization transfer imaging. Despite the abundance of available testing modalities, no single test is considered sensitive enough to be used alone to evaluate cognitive status in MS. NP algorithms, starting with short screening evaluations, followed by more extensive batteries if certain abnormalities are identified, represent the best approach in clinical practice.

This short review will provide a brief summary of the recent advances in NP testing, their correlates with MRI and clinical metrics considering future avenues for a better assessment of cognition in MS patients.

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