Nonlinear Associations Between Plasma Cholesterol Levels and Neuropsychological Function

Objective: Although both high and low levels of total and low-density lipoprotein (LDL) cholesterol have been associated with poor neuropsychological function, little research has examined nonlinear effects. We examined quadratic relations of cholesterol to performance on a comprehensive neuropsychological battery. Method: Participants were 190 older adults (53% men, ages 54-83) free of major medical, neurologic, and psychiatric disease. Measures of fasting plasma total and high-density lipoprotein (HDL) cholesterol were assayed, and LDL cholesterol was calculated. Participants completed neuropsychological measures of attention, executive function, memory, visuospatial judgment, and manual speed and dexterity. Multiple regression analyses examined cholesterol levels as quadratic predictors of each measure of cognitive performance, with age (dichotomized as <70 vs. 70+) as an effect modifier. Results: A significant quadratic effect of Total Cholesterol(2) x Age was identified for Logical Memory II (b = -.0013, p = .039), such that the 70+ group performed best at high and low levels of total cholesterol than at midrange total cholesterol (U-shaped) and the <70 group performed worse at high and low levels of total cholesterol than at midrange total cholesterol (inverted U shape). Similarly, significant U- and J-shaped effects of LDL Cholesterol(2) x Age were identified for Visual Reproduction II (b = -.0020, p = .026) and log of the Trail Making Test, Part B (b = .0001, p = .044). Quadratic associations between HDL cholesterol and cognitive performance were nonsignificant. Conclusions: Results indicate differential associations between cholesterol and neuropsychological function across different ages and domains of function. High and low total and LDL cholesterol may confer both risk and benefit for suboptimal cognitive function at different ages.