ABSTRACT. In this prospective study we examined whether total cholesterol and the oxysterols 24S- and 27-hydroxycholesterol were related to cognitive performance and rate of cognitive decline in elderly, and whether these associations were modified by ApoE _4. Data were collected during 6 years of follow-up as part of the Longitudinal Aging Study Amsterdam (N= 1181, age ?65 years), and analyzed using generalized estimating equations. Cognitive performance was measured with the mini-mental state examination (general cognition), the auditory verbal learning test (memory) and the coding task (information processing speed). Lower cholesterol at baseline was negatively associated with both general cognition (p = .012) and information processing speed (p = .045). ApoE modified the association between cholesterol and cognitive decline, and the association between the ratio of 27-hydroxycholesterol to cholesterol and cognitive functioning. In ApoE _4 carriers, lower cholesterol was related to a higher rate of decline on information processing speed (p = .006), and a higher ratio of 27-hydroxycholesterol to cholesterol was related to a lower level of general performance (p = .002) and memory functioning (p = .045). The results implicate that lower total cholesterol may be considered as a frailty marker, predictive of lower cognitive functioning in elderly.
