We evaluated cerebral glucose metabolism (CMRglc) and cerebrospinal fluid (CSF) levels of tau and beta-amyloid(1-42) (Abeta42), in relation to apolipoprotein E (ApoE) genotype, in patients with mild Alzheimer disease (AD) treated with rivastigmine (n=11) and tacrine (n=16) for 1 year; and two untreated AD groups. The rivastigmine-treated AD patients showed a significant increase in CMRglc as compared to both tacrine-treated and untreated AD subjects. The rivastigmine-treated AD group showed no change in CSF-tau levels after 1 year, while in contrast a significant increase as seen in tacrine-treated and untreated AD patients. The CSF-tau changes were mainly seen in ApoE epsilon4 carriers. There was no significant change in Abeta42 after 1-year treatment with either rivastigmine or tacrine. This study shows that the two long-term cholinesterase inhibitor treatments exert different effects on biological markers for AD.