Low Cholesterol Level Linked to Reduced Semantic Fluency Performance and Reduced Gray Matter Volume in the Medial Temporal Lob

Hyperlipidemia has been proposed as a risk factor of dementia and cognitive decline. However, the findings of relationship between cholesterol level and cognitive/brain function have been inconsistent. Here using a well-controlled sample from the Parkinson's Progression Markers Initiative (PPMI), we investigated the probable non-linear relationship between plasma total cholesterol (TC) level, gray matter volume (GMv), and cognitive performance in 117 subjects (mean age, 61.5±8.9). Within the subjects with a desirable TC level (TC = 200 mg/dl). Further ROI-based analysis showed that individuals with TC levels ranged from 100 to 160 mg/dl had the lowest GMv in the medial temporal regions. These findings suggest that low-normal TC level may be associated with reduced cognitive function and brain atrophy in regions implicated in neurodegenerative diseases, adding to a growing body of literature supporting low-normal cholesterol level (i.e., TC < 160 mg/dl) might have a detrimental effect on both cognition and brain health.