Stacey E Aaron1, Tsubasa Tomoto2,3, Rong Zhang2,3,4, John P Thyfault5,6,7,8,9, Eric D Vidoni1,9, Robert N Montgomery10, Jeffrey M Burns9, Sandra A Billinger11,12,13,14. 1. Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA. 2. Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, TX, USA. 3. Human Informatics and Interaction Research Institute, National Institute of Advanced Industrial Science and Technology, Ibaraki, Japan. 4. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA. 5. Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA. 6. Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA. 7. Research Service, Kansas City Veterans Affairs Medical Center, Kansas City, KS, USA. 8. Center for Children's Healthy Lifestyles and Nutrition, Kansas City, MO, USA. 9. University of Kansas Alzheimer's Research Disease Center, Fairway, KS, USA. 10. Department of Biostatistics and Data Science, University of Kansas Medical Center, Kansas City, KS, USA. 11. Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA. sbillinger@kumc.edu. 12. Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA. sbillinger@kumc.edu. 13. University of Kansas Alzheimer's Research Disease Center, Fairway, KS, USA. sbillinger@kumc.edu. 14. Department of Physical Medicine and Rehabilitation, University of Kansas Medical Center, Kansas City, KS, USA. sbillinger@kumc.edu.
Abstract
PURPOSE: It is plausible that statins could improve cerebral blood flow through pleiotropic mechanisms. The purpose of this investigation was to assess the contribution of statins to cerebrovascular variables in older adults with dyslipidemia and familial history of dementia. Furthermore, we explored the interaction between statin use and sex due to prevalent bias in statin trials. METHODS: Middle cerebral artery blood flow velocity (MCAv) was measured using transcranial Doppler ultrasound. Continuous supine rest recordings lasted 8 min. Participants included in analyses were statin (n = 100) or non-statin users (n = 112). RESULTS: MCAv and cerebrovascular conductance were significantly higher in statin users (p = 0.047; p = 0.04), and pulsatility index (PI) was significantly lower in statin users (p < 0.01). An interaction effect between statin use and sex was present for PI (p = 0.02); female statin users had significantly lower cerebrovascular resistance than the other three groups. CONCLUSION: In this cross-sectional analysis, statin use was positively associated with cerebrovascular variables in older adults at risk for dementia. Female statin users had significantly higher resting MCAv and cerebrovascular conductance than female non-statin users. The greatest contribution of statin use was the association with reduced cerebrovascular resistance. Given that cerebrovascular dysregulation is one of the earliest changes in Alzheimer's disease and related dementia pathology, targeting the cerebrovasculature with statins may be a promising prevention strategy.
PURPOSE: It is plausible that statins could improve cerebral blood flow through pleiotropic mechanisms. The purpose of this investigation was to assess the contribution of statins to cerebrovascular variables in older adults with dyslipidemia and familial history of dementia. Furthermore, we explored the interaction between statin use and sex due to prevalent bias in statin trials. METHODS: Middle cerebral artery blood flow velocity (MCAv) was measured using transcranial Doppler ultrasound. Continuous supine rest recordings lasted 8 min. Participants included in analyses were statin (n = 100) or non-statin users (n = 112). RESULTS: MCAv and cerebrovascular conductance were significantly higher in statin users (p = 0.047; p = 0.04), and pulsatility index (PI) was significantly lower in statin users (p < 0.01). An interaction effect between statin use and sex was present for PI (p = 0.02); female statin users had significantly lower cerebrovascular resistance than the other three groups. CONCLUSION: In this cross-sectional analysis, statin use was positively associated with cerebrovascular variables in older adults at risk for dementia. Female statin users had significantly higher resting MCAv and cerebrovascular conductance than female non-statin users. The greatest contribution of statin use was the association with reduced cerebrovascular resistance. Given that cerebrovascular dysregulation is one of the earliest changes in Alzheimer's disease and related dementia pathology, targeting the cerebrovasculature with statins may be a promising prevention strategy.
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