Cholesterol-metabolism, Plant Sterols, and Long-Term Cognitive Decline in Older People – Effects of Sex and APOEe4

Neurodegenerative, vascular, and dementia diseases are linked to dysregulations in cholesterol metabolism. Dietary plant sterols, or phytosterols, may interfere to neurodegeneration and cognitive decline, and have cholesterol-lowering, anti-inflammatory, and antioxidant qualities. Here, we investigated the potential associations between circulating cholesterol precursors and metabolites, triglycerides, and phytosterols with cognitive decline in older people by performing multivariate analysis on 246 participants engaged in a population-based prospective study. In our analysis we considered the potential effect of sex and APOEe4. We reveal particular dysregulations of diet-derived phytosterols and endogenous cholesterol synthesis and metabolism, and their variations over time linked to cognitive decline in the general population. These results are significant to the development of interventions to avoid cognitive decline in older adults and suggest that levels of circulating sterols should be taken into account when evaluating risk.