The Influence of Cholesterol on Resting Brain Blood Flow and Cognition in Middle-Aged Adults

Abstract

Total cholesterol increases with age, with peak values observed in middle-aged adults (50-64 years old). Middle-aged adults are vulnerable to experiencing future cognitive decline, in which the concurrent reductions in resting brain blood flow with aging have been linked to cognitive impairments. PURPOSE: To determine the influence of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol on resting brain blood flow and cognition in middle-aged adults (50-64 years old). Methods: LDL and HDL cholesterol were measured in 18 healthy adults (57 ± 4 years old). Resting cerebral and hippocampal blood flow were assessed using a pseudo-continuous arterial spin labeling (pCASL) sequence from the Human Connectome Project inside a Siemens Prisma 3T MRI scanner. Cognitive function was assessed using the Hopkins Verbal Learning Test (HVLT) and the National Institute of Health (NIH) Toolbox’s Flanker Inhibitory Control and Attention Test and Pattern Comparison Processing Speed Test. The influence of cholesterol on resting brain blood flow and cognition was analyzed using Pearson correlations. Results: LDL cholesterol (123 ± 23 mg/dL) was negatively correlated with resting cerebral (70.1 ± 12.5 ml.100g−1.min−1; r = -0.78, p = 0.0001) and hippocampal (67.6 ± 13.1 ml.100g−1.min−1; r = -0.74, p = 0.0005) blood flow. There were no significant associations for HDL cholesterol (67 ± 17 mg/dL) on resting cerebral (r = -0.03, p = 0.9) nor hippocampal (r = -0.04, p = 0.9) blood flow. Among the cognitive function tests, only hippocampal-dependent memory retention from the HVLT was positively associated with HDL cholesterol (r = 0.51, p = 0.03). A follow-up analysis revealed participants with a higher resting brain blood flow presented a tendency for higher scores in the Pattern Comparison Processing Speed Test (r = 0.44, p = 0.06). CONCLUSION: LDL cholesterol, a cardiometabolic risk factor, was negatively associated with resting cerebral and hippocampal blood flow whereas the potentially cardioprotective factor HDL cholesterol was not. HDL cholesterol was positively associated with memory-related outcomes. Our results suggest cholesterol may impact resting brain blood flow and should be considered a target in preventing or delaying age-related memory loss. Further data are required to elucidate the underlying mechanisms. SIGNIFANCE: The cardiometabolic effects of cholesterol may have additional implications on cerebrovascular and brain health. NIH/NIGMS - P20 GM113125. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.