Effects of Mitochondrial-targeted Antioxidant on Mild Cognitive Impairment (MCI) Patients
Study Details
Study Description
Brief Summary
Neurodegenerative diseases such as Mild Cognitive Impairment, Alzheimer's, and dementia affect millions of Americans. Although these diseases are heavily researched, there is very little research examining the impact of attenuated carotid artery endothelial function and cerebrovascular blood flow on cognitive function. This is surprising, as cerebrovascular oxygenation has been shown to be strongly associated with reduced cognitive function and the pathogenesis of neurodegenerative diseases. For example, hypertension, diabetes, and high cholesterol have been shown to increase the risk of Alzheimers related dementia. Therefore, the purpose of this proposed study will be to examine the effects of MitoQ supplementation on carotid artery vasodilatory function and cerebrovascular blood flow in those suffering from Mild Cognitive Impairment (MCI). MitoQ is a mitochondria-targeting antioxidant that can improve nitric oxide production in the blood vessel, which should improve endothelial function, and thus cerebrovascular blood flow.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
Metabolic disease parameters, such as hyperlipidemia and hypertension have been observed in Alzheimer's disease and dementia. The causes of neurodegenerative diseases like Alzheimers are not completely understood. However, increasing amounts of evidence are pointing to vascular dysfunction as a cause of this disease. Known as the vascular hypothesis, pathology is suggested to begin with cerebral hypoperfusion through attenuated blood flow via clogged carotid arteries. Hypoperfusion of cerebral cells means that they do not receive enough oxygen to function optimally. This lack of oxygen is believed to lead to cognitive impairment. It is hypothesized that these metabolic conditions can damage the endothelial wall, leading to impaired vasodilation and blood flow. This damage occurs in the carotid arteries, which would limit blood flow to the brain. This impaired blood flow also results from higher levels of reactive oxygen species (ROS), which reduce the bioavailability of nitric oxide (NO), an important vasodilator. Antioxidants, such as MitoQ, reduce these ROS and thus increase the NO availability, which improves endothelial function. This study will measure the use of the antioxidant MitoQ to reduce this endothelial dysfunction, thereby improving blood flow in the carotid arteries. Blood vessel health can be measured by how much bigger or smaller a vessel can become, because the ability of the vessel to change size is very important to make sure that blood is delivered to the tissues of the body. This study is being done to help us understand if endothelial dysfunction in Mild Cognitive Impairment (MCI) patients leads to the pathogenesis of the disease.
We will examine how endothelial function and cerebrovascular blood flow changes after consumption of MitoQ. We hope to achieve this through measures of carotid artery blood flow and brachial artery blood flow, using a doppler ultrasound for both, while using flow mediated dilation when measuring the brachial artery. The flow-mediated dilation test is a validated and safe assessment of endothelial function and vascular health. The premise behind the assessment is that endothelium produces autocoids, like nitric oxide, that dilate in response to shear stress. Flow-mediated dilation has been shown to be an effective tool to assess endothelial function in the peripheral and coronary vasculature. This assessment of endothelial health can be used in healthy individuals to detect risk for cardiovascular disease. We will also utilize near infrared spectroscopy to measure tissue oxygenation in the brain, which is also a measure of improved blood flow, and will measure brain neural activity with an EEG. Finally, we will collect blood samples to measure the change in ROS levels before and after MitoQ consumption
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MitoQ-Placebo Subjects will be tested on two different days, first day will be baseline and MitoQ intake, and second day will be placebo intake. Testing will take place 40-minutes after MitoQ and placebo intake. There will be a 2-week washout between testing days. |
Dietary Supplement: MitoQ
MitoQ is a mitochondria-targeting antioxidant, which should improve NO bioavailability, and therefore vasodilation
Dietary Supplement: Placebo
A placebo will be used in a double blinded, randomized, cross-over design
|
| Experimental: Placebo-MitoQ Subjects will be tested on two different days, first day will be baseline and placebo intake, and second day will be MitoQ intake. Testing will take place 40-minutes after placebo and MitoQ intake. There will be a 2-week washout between testing days. |
Dietary Supplement: MitoQ
MitoQ is a mitochondria-targeting antioxidant, which should improve NO bioavailability, and therefore vasodilation
Dietary Supplement: Placebo
A placebo will be used in a double blinded, randomized, cross-over design
|
Outcome Measures
Primary Outcome Measures
- Carotid artery blood flow [2 Days]
Blood flow in the carotid artery will be measured with ultrasound
Secondary Outcome Measures
- Oxidative Stress [2 days]
Blood draws will be taken to measure oxidative stress markers in the blood
- Cerebrovascular Oxygenation [2 Days]
Near-infrared spectroscopy will be used to measure cerebrovascular oxygenation
- Brain Electrical Activity [2 Days]
EEG will measure brain electrical activity
- Endothelial Function [2 Days]
Flow-mediated dilation will be used to measure vasodilation in the brachial artery
Eligibility Criteria
Criteria
Inclusion Criteria:
-
be able to give written, informed consent
-
Have a clinical diagnosis of Mild Cognitive Impairment (MCI) verified by a medical doctor
-
have a stable blood pressure regimen, stable lipid regimen, stable diabetes regimen and risk factor control for 6 weeks.
-
Free of kidney, metabolic or cardiovascular disease, including hypertension (stage 2) and previous cardiac events
-
be between 50-85 years old
Exclusion Criteria:
-
All participants must be free from smoking and alcohol abuse
-
Not be taking prescription drugs (other than oral contraceptives, blood pressure lowering drugs, and metformin)
-
Must not be diagnosed with Alzheimer's disease.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The University of Nebraska at Omaha | Omaha | Nebraska | United States | 68182 |
Sponsors and Collaborators
- University of Nebraska
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Green DJ, Dawson EA, Groenewoud HM, Jones H, Thijssen DH. Is flow-mediated dilation nitric oxide mediated?: A meta-analysis. Hypertension. 2014 Feb;63(2):376-82. doi: 10.1161/HYPERTENSIONAHA.113.02044. Epub 2013 Nov 25. Review.
- Green DJ, Jones H, Thijssen D, Cable NT, Atkinson G. Flow-mediated dilation and cardiovascular event prediction: does nitric oxide matter? Hypertension. 2011 Mar;57(3):363-9. doi: 10.1161/HYPERTENSIONAHA.110.167015. Epub 2011 Jan 24. Review.
- Kelleher RJ, Soiza RL. Evidence of endothelial dysfunction in the development of Alzheimer's disease: Is Alzheimer's a vascular disorder? Am J Cardiovasc Dis. 2013 Nov 1;3(4):197-226. Review.
- Luchsinger JA, Reitz C, Honig LS, Tang MX, Shea S, Mayeux R. Aggregation of vascular risk factors and risk of incident Alzheimer disease. Neurology. 2005 Aug 23;65(4):545-51.
- 088-18