Nonlinear longitudinal trajectories of cholesterol and neuropsychological function

Prior literature has identified inconsistent longitudinal associations between total cholesterol and cognitive decline. The authors examined prospective nonlinear relations of coincident trajectories of total cholesterol and cognitive function among persons free of stroke, dementia, and other neurological disease.

Up to 1,601 participants from the Baltimore Longitudinal Study of Aging (aged 19-93, 51% male, 75% White) underwent fasting cholesterol measurement and neuropsychological assessment on up to 12 occasions (M = 3.2, SD = 2.1) over up to 19 years (M = 6.4, SD = 5.3) of follow-up. Mixed-effects regression analyses were adjusted for age, sex, race, education, systolic blood pressure, body mass index, cardiovascular disease, lipid-lowering medication use, smoking, alcohol use, and depressive symptoms.

Analyses revealed significant longitudinal associations between quadratic total cholesterol and performance on measures of global mental status, verbal learning, executive function, and language (all ps < .05). In general, higher total cholesterol was associated with poorer middle-aged or young-old (60-69 years) cognitive performance, but better old-old (80-89 years) cognitive performance. Linear models also revealed an association between lower total cholesterol and accelerated decline in visual memory performance.

Overall, results indicate nonlinear longitudinal relations of total cholesterol to cognitive decline. Whereas higher cholesterol levels were associated with cognitive decline in the middle-aged or young-old, lower cholesterol levels were related to cognitive decline among old-old participants.