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| ID | Type | Description | Link |
|---|---|---|---|
| K23AG026752 | U.S. NIH Grant/Contract | View source | |
| Pilot Award | Other Grant/Funding Number | Wisconsin Comprehensive Memory Program Pilot Award |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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The purpose of this study is to evaluate the hypothesis that in middle-aged, asymptomatic, adult children of persons with Alzheimer's disease (AD), atorvastatin therapy will beneficially affect mechanisms thought to contribute to AD risk by improving blood flow in the brain, improving cerebral perfusion, increasing brain activity patterns, and improving blood vessel function.
Treatment with cholesterol-lowering medications, specifically statins, is associated with up to a 73% reduction in the prevalence of AD, suggesting a potentially promising role for statins in the prevention of AD. In order to better understand the mechanisms through which statins may possibly modify blood AD risk, this study evaluated whether administration of atorvastatin favorably altered blood flow in the brain (measured by magnetic resonance imaging (MRI)) and blood vessel function (measured by ultrasound).
Participants attended 3 visits over the course of the 4-month study. At the initial visit, participants completed a short questionnaire about their past medical history and medication history. At the baseline visit, participants were randomized in a 1:1 ratio to receive atorvastatin 40 mg nightly vs. matching placebo. At baseline and follow-up visits, participants provided an update on medical problems and medications, reviewed any potential side effects, and had fasting blood tests collected for safety monitoring, including liver and muscle enzyme monitoring. In addition, all participants had MRI and ultrasound measures collected.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Atorvastatin | Experimental | 40mg Atorvastatin nightly for 4 months |
|
| Placebo | Placebo Comparator | matching placebo nightly for 4 months |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| atorvastatin | Drug | 40mg daily for 4 months |
|
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| Measure | Description | Time Frame |
|---|---|---|
| Change in regional cerebral blood flow (rCBF) | rCBF , a measure of cerebral perfusion, is the primary outcome. rCBF was measured by arterial spin-labeling magnetic resonance imaging and used to evaluate effects of atorvastatin vs placebo | Baseline and 4 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Endothelial function | Brachial artery reactivity was used to measure endothelial function | Baseline and 4 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Cynthia M. Carlsson, MD, MS | University of Wisconsin, Madison | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Karen Lazar | Madison | Wisconsin | 53705 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 14523972 | Background | Newman GC, Delucia-Deranja E, Tudorica A, Hospod FE, Patlak CS. Cerebral blood volume measurements by T*2-weighted MRI and contrast infusion. Magn Reson Med. 2003 Oct;50(4):844-55. doi: 10.1002/mrm.10591. | |
| 7547018 | Background | Sorensen KE, Celermajer DS, Spiegelhalter DJ, Georgakopoulos D, Robinson J, Thomas O, Deanfield JE. Non-invasive measurement of human endothelium dependent arterial responses: accuracy and reproducibility. Br Heart J. 1995 Sep;74(3):247-53. doi: 10.1136/hrt.74.3.247. |
| Label | URL |
|---|---|
| Wisconsin Alzheimer's Disease Research Center | View source |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000069059 | Atorvastatin |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Placebo | Drug | Matching placebo daily for 4 months |
|
| 14697473 | Background | Wassmann S, Ribaudo N, Faul A, Laufs U, Bohm M, Nickenig G. Effect of atorvastatin 80 mg on endothelial cell function (forearm blood flow) in patients with pretreatment serum low-density lipoprotein cholesterol levels <130 mg/dl. Am J Cardiol. 2004 Jan 1;93(1):84-8. doi: 10.1016/j.amjcard.2003.09.018. |
| 10477529 | Background | Stein JH, Keevil JG, Wiebe DA, Aeschlimann S, Folts JD. Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease. Circulation. 1999 Sep 7;100(10):1050-5. doi: 10.1161/01.cir.100.10.1050. |
| 12686036 | Background | Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J; ASCOT investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003 Apr 5;361(9364):1149-58. doi: 10.1016/S0140-6736(03)12948-0. |
| 22175654 | Result | Carlsson CM, Xu G, Wen Z, Barnet JH, Blazel HM, Chappell RJ, Stein JH, Asthana S, Sager MA, Alsop DC, Rowley HA, Fain SB, Johnson SC. Effects of atorvastatin on cerebral blood flow in middle-aged adults at risk for Alzheimer's disease: a pilot study. Curr Alzheimer Res. 2012 Oct;9(8):990-7. doi: 10.2174/156720512803251075. |
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D006538 |
| Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |