Identifying risk factors for cognitive issues in multiple sclerosis

ABSTRACT

Introduction: Cognitive impairment (CI) in Multiple Sclerosis (MS) has progressively regained clinical and research interest and is currently recognized as a debilitating and burdensome problem for these patients. Studying risk and protecting factors that may influence the development and course of CI is currently an area of increasing interest, due to the potential for preventive strategies.

Areas covered: In this narrative review the authors briefly addressed the physiopathologic basis, assessment and management of CI in MS and then focused on identifying modifiable and not modifiable risk factors for CI in MS, providing an overview of the current knowledge in the field and indicating avenues for future research.

Expert opinion: Improving our understanding of potentially modifiable environmental and lifestyle risk factors or protective factors for CI is important in order to prompt preventive strategies and orient patient counselling and clinical management. To this aim, we need to enhance the current level of evidence linking lifestyle factors to cognition and evaluate some factors that were only preliminary addressed in research. Moreover, we need to explore the role of each factor into the subject cognitive outcome, next to the possible interactions between different environmental factors as well as between environmental and genetic factors.

KEYWORDS:

• Multiple sclerosis
• cognitive impairment
• risk factors
• protective factors
• cognitive assessment

Article highlights

• In MS, both inflammation and neurodegeneration in the WM and cortical and subcortical GM contribute to the burden of cognitive impairment (CI), a common and debilitating symptom present in up to 70% of the patients.

• Information processing speed, memory and executive functions are the domains most frequently impaired.

• Systematic assessment of cognitive functioning through brief neuropsychological batteries should be integrated in daily practice.

• Older age and higher disability levels are associated with CI, independently from other demographic or disease-related measures.

• Progressive disease course is a risk factor for CI, thus progressive MS patients may benefit from early, targeted interventions.

• Psychiatric comorbidities and fatigue are common in MS and represent modifiable RFs for CI.

• Brain reserve and cognitive reserve are two important protecting factors although their role may be limited to the early disease stages.

• The search for genetic risk factors for CI in MS has been limited and so far has provided mainly negative or inconsistent results.

• Other poorly understood but potentially modifiable RFs/PFs include physical exercise, mentally active lifestyles, comorbidities, smoking, alcohol, pain and sleep abnormalities.

• It is important to improve the level of evidence linking the above-mentioned lifestyle factors to cognition, and better explore a few factors that were only preliminarily evaluated in research or ignored at the moment like diet, vitamin D and stress.

• Future research should also explore to what extent each risk or protective factor makes independent contribution to the subject cognitive outcome and assess possible interactions between different environmental factors as well as between environmental and genetic factors

Declaration of interest

MP Amato received research grants and honoraria as a speaker and member of advisory boards from: Bayer, Biogen, Merck, Novartis, Sanofi Genzyme, Teva, Almirall and Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.