Effect of simvastatin on CSF Alzheimer disease biomarkers in cognitively normal adults

Ge Li, Cynthia L. Mayer, Daniel Morelli, Steven P. Millard, Wendy H. Raskind, Eric C. Petrie, Monique Cherrier, Anne M. Fagan, Murray A. Raskind, Elaine R. Peskind

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Objective: To examine potential disease-modifying effects of statin drugs, we conducted a 12-month randomized, placebo-controlled clinical trial of simvastatin in cognitively normal adults using change in CSF Alzheimer disease biomarkers as primary outcome measure. Methods: Participants were 45-64 years old and statin-naive with normal cognition and normal or mildly elevated cholesterol. Forty-six participants completed the 1-year study per protocol (25 in the simvastatin and 21 in the placebo group). Simvastatin was titrated to 40 mg/d. CSF Aβ 42, total tau, and p-tau 181 were measured at baseline and after 12 months of treatment using the INNO-BIA AlzBio3 assay. We used analysis of covariance to assess differences in biomarker change from baseline between treatment groups, adjusting for age, sex, and APOE ϵ4 status. Results: Changes from baseline did not differ significantly between treatment groups for any CSF biomarker, with p values of 0.53, 0.36, and 0.25 for CSF Aβ 42, total tau, and p-tau 181, respectively. There was no significant modifying effect of sex, APOE ϵ4, or baseline high-density lipoprotein or triglycerides on treatment group for any of the biomarkers (all p > 0.18). However, a significant interaction between treatment group and baseline low-density lipoprotein (LDL) was observed for p-tau 181 (p = 0.003), where greater decreases from baseline in CSF p-tau 181 concentrations were associated with higher baseline LDL level for the simvastatin group. Conclusions: Simvastatin-related reductions in CSF p-tau 181 concentrations may be modulated by LDL cholesterol. The potential disease-modifying effects of simvastatin on CSF phospho-tau should be further investigated in persons with hypercholesterolemia.

Original languageEnglish
Pages (from-to)1251-1255
Number of pages5
Issue number12
StatePublished - Sep 19 2017


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