BACKGROUND: The associations of apolipoprotein E (ApoE) genotypes and cholesterol levels with cognitive decline in Alzheimer's disease (AD) are controversial. The aim of this study is to investigate the individual and combined effects of ApoE epsilon 4 allele (Epsilon4) and cholesterol levels on the progression of AD. METHODS: ApoE genotypes and fasting serum total cholesterol levels were measured in 79 patients with AD. The associations were investigated between Epsilon4, cholesterol level and decline in cognitive function (Korean version of Mini-Mental State Examination) over one year. RESULTS: No prospective individual and combined associations were found between Epsilon4, cholesterol level and decline of cognitive function. Adjustment for age, gender, education, and functional activities of daily living made little difference to the associations. CONCLUSIONS: The cognitive decline of AD might be determined by other factors rather than the impact of Epsilon4 or cholesterol levels.