Ge Li1, Cynthia L Mayer2, Daniel Morelli2, Steven P Millard2, Wendy H Raskind2, Eric C Petrie2, Monique Cherrier2, Anne M Fagan2, Murray A Raskind2, Elaine R Peskind2. 1. From the Geriatric Research, Education, and Clinical Center (G.L., W.H.R.) and Northwest Network (VISN-20) Mental Illness, Research, Education, and Clinical Center (G.L., C.L.M., D.M., S.P.M., E.C.P., M.A.R., E.R.P.), Veterans Affairs Puget Sound Health Care System; Departments of Psychiatry and Behavioral Sciences (G.L., E.C.P., M.C., M.A.R., E.R.P.) and Medicine (W.H.R.), University of Washington, Seattle; and Department of Neurology (A.M.F.), Washington University in St. Louis, MO. gli@uw.edu. 2. From the Geriatric Research, Education, and Clinical Center (G.L., W.H.R.) and Northwest Network (VISN-20) Mental Illness, Research, Education, and Clinical Center (G.L., C.L.M., D.M., S.P.M., E.C.P., M.A.R., E.R.P.), Veterans Affairs Puget Sound Health Care System; Departments of Psychiatry and Behavioral Sciences (G.L., E.C.P., M.C., M.A.R., E.R.P.) and Medicine (W.H.R.), University of Washington, Seattle; and Department of Neurology (A.M.F.), Washington University in St. Louis, MO.
Abstract
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 Aβ42, total tau, and p-tau181 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 Aβ42, total tau, and p-tau181, 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-tau181 (p = 0.003), where greater decreases from baseline in CSF p-tau181 concentrations were associated with higher baseline LDL level for the simvastatin group. CONCLUSIONS: Simvastatin-related reductions in CSF p-tau181 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.
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 Aβ42, total tau, and p-tau181 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 Aβ42, total tau, and p-tau181, 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-tau181 (p = 0.003), where greater decreases from baseline in CSF p-tau181 concentrations were associated with higher baseline LDL level for the simvastatin group. CONCLUSIONS: Simvastatin-related reductions in CSF p-tau181 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.
Authors: Robert G Riekse; Ge Li; Eric C Petrie; James B Leverenz; Darcy Vavrek; Simona Vuletic; John J Albers; Thomas J Montine; Virginia M-Y Lee; Michael Lee; Peter Seubert; Douglas Galasko; Gerard D Schellenberg; William R Hazzard; Elaine R Peskind Journal: J Alzheimers Dis Date: 2006-12 Impact factor: 4.472
Authors: G Li; E B Larson; J A Sonnen; J B Shofer; E C Petrie; A Schantz; E R Peskind; M A Raskind; J C S Breitner; T J Montine Journal: Neurology Date: 2007-08-28 Impact factor: 9.910
Authors: Julius Popp; Sabrina Meichsner; Heike Kölsch; Piotr Lewczuk; Wolfgang Maier; Johannes Kornhuber; Frank Jessen; Dieter Lütjohann Journal: Biochem Pharmacol Date: 2013-01-03 Impact factor: 5.858
Authors: Cynthia M Carlsson; Carey E Gleason; Timothy M Hess; Kimberly A Moreland; Hanna M Blazel; Rebecca L Koscik; Nathan T N Schreiber; Sterling C Johnson; Craig S Atwood; Luigi Puglielli; Bruce P Hermann; Patrick E McBride; James H Stein; Mark A Sager; Sanjay Asthana Journal: J Alzheimers Dis Date: 2008-03 Impact factor: 4.472
Authors: V Leduc; L De Beaumont; L Théroux; D Dea; P Aisen; R C Petersen; R Dufour; J Poirier Journal: Mol Psychiatry Date: 2014-07-15 Impact factor: 15.992
Authors: Irundika H K Dias; Ivana Milic; Gregory Y H Lip; Andrew Devitt; M Cristina Polidori; Helen R Griffiths Journal: Redox Biol Date: 2018-02-17 Impact factor: 11.799
Authors: Leon Stefanovski; Jil Mona Meier; Roopa Kalsank Pai; Paul Triebkorn; Tristram Lett; Leon Martin; Konstantin Bülau; Martin Hofmann-Apitius; Ana Solodkin; Anthony Randal McIntosh; Petra Ritter Journal: Front Neuroinform Date: 2021-04-01 Impact factor: 4.081