Long-Term Statin Therapy and CSF Cholesterol Levels: Implications for Alzheimer’s Disease

Background/Aims: It is not yet established whether statins (lipophilic or hydrophilic) reduce the risk of Alzheimer’s disease and, if so, by differentially modifying brain lipid levels. Our aim was to assess changes in brain cholesterol metabolism as reflected in the cerebrospinal fluid (CSF) before and after treatment with either atorvastatin or simvastatin. Methods: We carried out a longitudinal analysis of CSF cholesterol, lathosterol and 24(S)-hydroxycholesterol before and after treatment with maximum doses of statins in 10 asymptomatic subjects, 8 of whom were heterozygous for apolipoprotein E ε4, and in 6 presymptomatic PS1 subjects. Results: Statins initially reduced CSF lathosterol cholesterol and 24(S)-hydroxycholesterol in both PS1 and non-PS1 subjects reaching a nadir at 6–7 months, followed by a return to baseline at 15 months with an overshoot at 2 years, tending to return to baseline thereafter. Conclusions: Possible long-term protective effects of statins are not likely largely related to the temporally-dependent biphasic effects of statin therapy upon the magnitude and direction of changes in CSF lipid levels and their subsequent return to baseline levels.