Dejan Jakimovski1, Robert Zivadinov2, Michael G Dwyer1, Niels Bergsland1, Deepa P Ramasamy1, Richard W Browne3, Bianca Weinstock-Guttman4, Murali Ramanathan5. 1. Buffalo Neuroimaging Analysis Center (BNAC), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA. 2. Buffalo Neuroimaging Analysis Center (BNAC), Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA; Center for Biomedical Imaging at Clinical Translational Science Institute, University at Buffalo, State University of New York, Buffalo, NY, USA. 3. Department of Biotechnical and Clinical Laboratory Sciences, State University of New York, Buffalo, NY, USA. 4. Jacobs Comprehensive MS Treatment and Research Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, NY, USA. 5. Department of Pharmaceutical Sciences, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA. Electronic address: murali@buffalo.edu.
Abstract
BACKGROUND: The pathophysiological mechanisms underlying the associations of multiple sclerosis (MS) neurodegeneration serum cholesterol profiles is currently unknown. OBJECTIVE: To determine associations between lipid profile measures and cerebral perfusion-based indices in MS patients. METHODS: Seventy-seven MS patients underwent 3 T MRI. Cerebral blood volume (CBV), time-to-peak (TTP) and mean transit time (MTT) measures were computed from dynamic susceptibility contrast (DSC) perfusion-weighted imaging (PWI) for normal-appearing brain tissue (NABT), GM, cortex, deep gray matter (DGM) and thalamus. Total cholesterol, low and high-density lipoprotein cholesterol (LDL-C and HDL-C) and the apolipoproteins (Apo), ApoA-I, ApoA-II, ApoB, ApoC-II and ApoE levels were measured in plasma. Age and body mass index (BMI)-adjusted correlations were used to assess the associations between PWI and lipid profile measures. RESULTS: Higher HDL-C levels were associated with shorter MTT, which are indicative of greater perfusion, in NABT (p = 0.012), NAWM (p = 0.021), GM (p = 0.009), cortex (p = 0.014), DGM p = 0.015; and thalamus p = 0.015). The HDL-C-associated apolipoproteins, ApoA-I and ApoA-II, were associated with shorter MTT of the same brain regions (all p < 0.028). HDL-C and ApoA-I levels were also associated with shorter TTP, indicative of faster cerebral blood delivery. ApoC-II was associated with lower nCBV of the GM and cortex (p = 0.035 and p = 0.014, respectively). CONCLUSION: The HDL pathway is associated with better global brain perfusion and faster cerebral blood delivery as measured by shorter MTT and TTP, respectively. ApoC-II may be associated with lower cortical and DGM perfusion.
BACKGROUND: The pathophysiological mechanisms underlying the associations of multiple sclerosis (MS) neurodegeneration serum cholesterol profiles is currently unknown. OBJECTIVE: To determine associations between lipid profile measures and cerebral perfusion-based indices in MS patients. METHODS: Seventy-seven MS patients underwent 3 T MRI. Cerebral blood volume (CBV), time-to-peak (TTP) and mean transit time (MTT) measures were computed from dynamic susceptibility contrast (DSC) perfusion-weighted imaging (PWI) for normal-appearing brain tissue (NABT), GM, cortex, deep gray matter (DGM) and thalamus. Total cholesterol, low and high-density lipoprotein cholesterol (LDL-C and HDL-C) and the apolipoproteins (Apo), ApoA-I, ApoA-II, ApoB, ApoC-II and ApoE levels were measured in plasma. Age and body mass index (BMI)-adjusted correlations were used to assess the associations between PWI and lipid profile measures. RESULTS: Higher HDL-C levels were associated with shorter MTT, which are indicative of greater perfusion, in NABT (p = 0.012), NAWM (p = 0.021), GM (p = 0.009), cortex (p = 0.014), DGM p = 0.015; and thalamus p = 0.015). The HDL-C-associated apolipoproteins, ApoA-I and ApoA-II, were associated with shorter MTT of the same brain regions (all p < 0.028). HDL-C and ApoA-I levels were also associated with shorter TTP, indicative of faster cerebral blood delivery. ApoC-II was associated with lower nCBV of the GM and cortex (p = 0.035 and p = 0.014, respectively). CONCLUSION: The HDL pathway is associated with better global brain perfusion and faster cerebral blood delivery as measured by shorter MTT and TTP, respectively. ApoC-II may be associated with lower cortical and DGM perfusion.