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The role of cholesterol pathway biomarkers in multiple sclerosis is not fully understood. This article makes the case that these biomarkers may correlate with cognitive impairment.

Cholesterol pathway biomarkers are associated with breakdown of the blood-brain barrier, lesions, and neurodegeneration in patients with multiple sclerosis (MS). Cognitive impairment is common in these patients, and is further linked to neurodegeneration. This study, published in Multiple Sclerosis and Related Disorders, examines the possible link between cholesterol pathway biomarkers and cognitive impairment. The study used a cross-sectional design and included 74 relapsing–remitting patients with MS, 48 patients with progressive MS, and 41 healthy controls.

Various tests were used to assess physical disability and cognitive measures, including the Nine-hole Peg Test, Timed 25-foot Walk, Symbol Digit Modalities Test, Paced Auditory Serial Addition Test-3, and Beck Depression Inventory-Fast Screen. The cholesterol pathway biomarker panel included plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and the apolipoproteins ApoA-I, ApoaA-II, ApoB, ApoC-II, and ApoE. Additional disability and cognitive measures were evaluated as dependent variables in regression analyses, which included age, sex, body mass index, and years of education. 

Results from the Symbol Digit Modalities Test were associated with the interaction terms for HDL-C, ApoA-I, ApoB, TC/HDL, and ApoB/ApoA-I ratios. Nine-hole Peg Test performance was associated with interaction terms for TC, LDL-C, ApoB, HDL-C, ApoA-I, ApoC-II, and ApoE. Because the Symbol Digit Modalities Test and Nine-hole Peg Test results were associated with multiple cholesterol pathway biomarkers, the authors conclude by noting that a potential role for cholesterol pathway biomarkers in cognitive impairment is consistent with these data. However, additional research is needed to confirm the data and to gain a better understanding of cognitive impairment in MS. 

Siddiqui, K., Browne, R. W., Benedict, R. H. B., Jakimovski, D., Weinstock-Guttman, B., Zivadinov, R., & Ramanathan, M. (2022). Cholesterol pathway biomarkers are associated with neuropsychological measures in multiple sclerosis. Mult Scler Relat Disord, 69, 104374. https://doi.org/10.1016/j.msard.2022.104374

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