Effects of simvastatin on white matter integrity in healthy middle‐aged adults
Abstract Background The brain is the most cholesterol‐rich organ and myelin contains 70% of total brain cholesterol. Statins are potent cholesterol‐lowing medications used by millions of adults for prevention of vascular disease, yet the effect of statins on cholesterol‐rich brain white matter (WM)...
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doaj-03af5eeaf0bd408c900b904e4a23acba2021-08-09T12:23:42ZengWileyAnnals of Clinical and Translational Neurology2328-95032021-08-01881656166710.1002/acn3.51421Effects of simvastatin on white matter integrity in healthy middle‐aged adultsNicholas M. Vogt0Jack F. V. Hunt1Yue Ma2Carol A. Van Hulle3Nagesh Adluru4Richard J. Chappell5Karen K. Lazar6Laura E Jacobson7Benjamin P. Austin8Sanjay Asthana9Sterling C. Johnson10Barbara B. Bendlin11Cynthia M. Carlsson12Wisconsin Alzheimer’s Disease Research Center University of Wisconsin School of Medicine and Public Health Madison WisconsinWisconsin Alzheimer’s Disease Research Center University of Wisconsin School of Medicine and Public Health Madison WisconsinWisconsin Alzheimer’s Disease Research Center University of Wisconsin School of Medicine and Public Health Madison WisconsinWisconsin Alzheimer’s Disease Research Center University of Wisconsin School of Medicine and Public Health Madison WisconsinWaisman Laboratory for Brain Imaging and Behavior Waisman Center University of Wisconsin‐Madison Madison WisconsinWisconsin Alzheimer’s Disease Research Center University of Wisconsin School of Medicine and Public Health Madison WisconsinWisconsin Alzheimer’s Disease Research Center University of Wisconsin School of Medicine and Public Health Madison WisconsinWisconsin Alzheimer’s Disease Research Center University of Wisconsin School of Medicine and Public Health Madison WisconsinWisconsin Alzheimer’s Disease Research Center University of Wisconsin School of Medicine and Public Health Madison WisconsinWisconsin Alzheimer’s Disease Research Center University of Wisconsin School of Medicine and Public Health Madison WisconsinWisconsin Alzheimer’s Disease Research Center University of Wisconsin School of Medicine and Public Health Madison WisconsinWisconsin Alzheimer’s Disease Research Center University of Wisconsin School of Medicine and Public Health Madison WisconsinWisconsin Alzheimer’s Disease Research Center University of Wisconsin School of Medicine and Public Health Madison WisconsinAbstract Background The brain is the most cholesterol‐rich organ and myelin contains 70% of total brain cholesterol. Statins are potent cholesterol‐lowing medications used by millions of adults for prevention of vascular disease, yet the effect of statins on cholesterol‐rich brain white matter (WM) is largely unknown. Methods We used longitudinal neuroimaging data acquired from 73 healthy, cognitively unimpaired, statin‐naïve, middle‐aged adults during an 18‐month randomized controlled trial of simvastatin 40 mg daily (n = 35) or matching placebo (n = 38). ANCOVA models (covariates: age, sex, APOE‐ɛ4) tested the effect of treatment group on percent change in WM, gray matter (GM), and WM hyperintensity (WMH) neuroimaging measures at each study visit. Mediation analysis tested the indirect effects of simvastatin on WM microstructure through change in serum total cholesterol levels. Results At 18 months, the simvastatin group showed a significant preservation in global WM fractional anisotropy (β = 0.88%, 95% CI 0.27 to 1.50, P = 0.005), radial diffusivity (β = −1.10%, 95% CI −2.13 to −0.06, P = 0.039), and WM volume (β = 0.72%, 95% CI 0.13 to 1.32, P = 0.018) relative to the placebo group. There was no significant effect of simvastatin on GM or WMH volume. Change in serum total cholesterol mediated approximately 30% of the effect of simvastatin on WM microstructure. Conclusions Simvastatin treatment in healthy, middle‐aged adults resulted in preserved WM microstructure and volume at 18 months. The partial mediation by serum cholesterol reduction suggests both peripheral and central mechanisms. Future studies are needed to determine whether these effects persist and translate to cognitive outcomes. Trial Registration NCT00939822 (ClinicalTrials.gov).https://doi.org/10.1002/acn3.51421 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nicholas M. Vogt Jack F. V. Hunt Yue Ma Carol A. Van Hulle Nagesh Adluru Richard J. Chappell Karen K. Lazar Laura E Jacobson Benjamin P. Austin Sanjay Asthana Sterling C. Johnson Barbara B. Bendlin Cynthia M. Carlsson |
spellingShingle |
Nicholas M. Vogt Jack F. V. Hunt Yue Ma Carol A. Van Hulle Nagesh Adluru Richard J. Chappell Karen K. Lazar Laura E Jacobson Benjamin P. Austin Sanjay Asthana Sterling C. Johnson Barbara B. Bendlin Cynthia M. Carlsson Effects of simvastatin on white matter integrity in healthy middle‐aged adults Annals of Clinical and Translational Neurology |
author_facet |
Nicholas M. Vogt Jack F. V. Hunt Yue Ma Carol A. Van Hulle Nagesh Adluru Richard J. Chappell Karen K. Lazar Laura E Jacobson Benjamin P. Austin Sanjay Asthana Sterling C. Johnson Barbara B. Bendlin Cynthia M. Carlsson |
author_sort |
Nicholas M. Vogt |
title |
Effects of simvastatin on white matter integrity in healthy middle‐aged adults |
title_short |
Effects of simvastatin on white matter integrity in healthy middle‐aged adults |
title_full |
Effects of simvastatin on white matter integrity in healthy middle‐aged adults |
title_fullStr |
Effects of simvastatin on white matter integrity in healthy middle‐aged adults |
title_full_unstemmed |
Effects of simvastatin on white matter integrity in healthy middle‐aged adults |
title_sort |
effects of simvastatin on white matter integrity in healthy middle‐aged adults |
publisher |
Wiley |
series |
Annals of Clinical and Translational Neurology |
issn |
2328-9503 |
publishDate |
2021-08-01 |
description |
Abstract Background The brain is the most cholesterol‐rich organ and myelin contains 70% of total brain cholesterol. Statins are potent cholesterol‐lowing medications used by millions of adults for prevention of vascular disease, yet the effect of statins on cholesterol‐rich brain white matter (WM) is largely unknown. Methods We used longitudinal neuroimaging data acquired from 73 healthy, cognitively unimpaired, statin‐naïve, middle‐aged adults during an 18‐month randomized controlled trial of simvastatin 40 mg daily (n = 35) or matching placebo (n = 38). ANCOVA models (covariates: age, sex, APOE‐ɛ4) tested the effect of treatment group on percent change in WM, gray matter (GM), and WM hyperintensity (WMH) neuroimaging measures at each study visit. Mediation analysis tested the indirect effects of simvastatin on WM microstructure through change in serum total cholesterol levels. Results At 18 months, the simvastatin group showed a significant preservation in global WM fractional anisotropy (β = 0.88%, 95% CI 0.27 to 1.50, P = 0.005), radial diffusivity (β = −1.10%, 95% CI −2.13 to −0.06, P = 0.039), and WM volume (β = 0.72%, 95% CI 0.13 to 1.32, P = 0.018) relative to the placebo group. There was no significant effect of simvastatin on GM or WMH volume. Change in serum total cholesterol mediated approximately 30% of the effect of simvastatin on WM microstructure. Conclusions Simvastatin treatment in healthy, middle‐aged adults resulted in preserved WM microstructure and volume at 18 months. The partial mediation by serum cholesterol reduction suggests both peripheral and central mechanisms. Future studies are needed to determine whether these effects persist and translate to cognitive outcomes. Trial Registration NCT00939822 (ClinicalTrials.gov). |
url |
https://doi.org/10.1002/acn3.51421 |
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