Cholesterol pathway biomarkers are associated with neuropsychological measures in multiple sclerosis

Mult Scler Relat Disord. 2023 Jan:69:104374. doi: 10.1016/j.msard.2022.104374. Epub 2022 Oct 31.

Abstract

Background: Cognitive impairment (CI) is frequent in persons with multiple sclerosis (PwMS) and is linked to neurodegeneration. Cholesterol pathway biomarkers (CPB) are associated with blood-brain barrier breakdown, lesions, and neurodegeneration in multiple sclerosis (MS). CPB could influence CI.

Methods: This cross-sectional study (n = 163) included 74 relapsing-remitting MS (RR-MS), 48 progressive MS (P-MS) and 41 healthy control (HC) subjects. The assessed physical disability and cognitive measures were: Nine-hole Peg Test (NHPT), Timed 25-Foot Walk, Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test-3, and Beck Depression Inventory-Fast Screen. CPB panel included plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and the apolipoproteins (Apo), ApoA-I, ApoA-II, ApoB, ApoC-II and ApoE. Disability and cognitive measures were assessed as dependent variables in regression analyzes with age, sex, body mass index, years of education, HC vs. RR-MS vs. P-MS status, CPB, and a HC vs. RR-MS vs. P-MS status × CPB interaction term as predictors.

Results: SDMT was associated with the interaction terms for HDL-C (p = 0.045), ApoA-I (p = 0.032), ApoB (p = 0.032), TC/HDL-C (p = 0.013), and ApoB/ApoA-I (p = 0.008) ratios. CPB associations of SDMT were not abrogated upon adjusting for brain parenchymal volume. NHPT performance was associated with the interaction terms for TC (p = 0.047), LDL-C (p = 0.017), ApoB (p = 0.001), HDL-C (p = 0.035), ApoA-I (p = 0.032), ApoC-II (p = 0.049) and ApoE (p = 0.037), TC/HDL-C (p < 0.001), and ApoB/ApoA-I ratios (p < 0.001).

Conclusions: The LDL to HDL proportion is associated with SDMT and NHPT in MS. The findings are consistent with a potential role for CPB in CI.

Keywords: Cholesterol; Cognitive impairment; Multiple sclerosis; Neurodegeneration; Primary progressive multiple sclerosis; Relapsing remitting multiple sclerosis.

MeSH terms

  • Apolipoprotein A-I
  • Apolipoproteins B
  • Apolipoproteins C
  • Apolipoproteins E
  • Biomarkers
  • Cholesterol
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Cross-Sectional Studies
  • Humans
  • Multiple Sclerosis* / complications
  • Multiple Sclerosis* / diagnosis

Substances

  • Apolipoprotein A-I
  • Cholesterol, LDL
  • Cholesterol
  • Cholesterol, HDL
  • Apolipoproteins B
  • Apolipoproteins E
  • Biomarkers
  • Apolipoproteins C