Evaluate the Effect of Atorvastatin on Cerebrovascular Reactivity in MCI

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of atorvastatin on brain vessel reactivity and with it on blood flow in people with mild cognitive impairment.

Detailed Description
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Participants are first being informed about potential benefits and risks of the study and are required to give written consent. After that participants will undergo detailed phone screen to determine eligibility for study entry. At week 0, participants who meet eligibility requirements will be prescribed atorvastatin (40 mg, once in the evening) in an open-label manner.

Official Title
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Targeting Cerebrovascular Reactivity for Precision Medicine: Pilot Trial of Atorvastatin

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Drug: Atorvastatin Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria are chosen to include participants with MCI, enriched for vascular risk factors: MCI defined by CDR of 0.5 or 1.0. Memory, processing speed, executive function, language - cognitive scores > 1.5 standard deviations below age-education norms. Not demented by history. Not taking statins currently or in the last 6 months. Cognitive/functional impairment not likely due to another neurological disease or delirium. Exclusion Criteria: Taking a statin currently or have taken a statin in the last 6 months. Contraindications to taking a statin. Transplant patient taking cyclosporine. Unable to undergo MRI procedures (such as having an implanted pacemaker or defibrillator or stimulator or having non MRI compatible metal). Diagnosis of dementia by history. Current diagnosis of substance abuse. History of stroke or myocardial infarction in past 6 months. History of HIV.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 95 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label study with atorvastatin 40 mg
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atorvastatin 40 mg<br>Participants receive 40 mg atorvastatin orally daily in the evening. | Drug: Atorvastatin Oral Tablet<br>* Atorvastatin pill 40 mg to be taken every night<br>* Other names: Lipitor oral tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of MRI whole brain cerebrovascular reactivity (wbCVR) | MRI based CVR is a newer technique that measures dilatory function of the microvessels which have been shown to be superior to measurement of Cerebral blood flow (CBF) and have also been shown to be low in participants with MCI. | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma exosomes | Endothelial-derived exosomes (EDE) reflect the neurochemistry of cerebrovascular endothelial cells, while neuronal-enriched extracellular vesicles (nEV) are associated with brain white matter hyperintensities. | Baseline and 12 weeks | 
| Change in cognitive function (global neurocognitive measure) | Assessed by Global neurocognitive measure. | Baseline and 12 weeks | 
| Change in cognitive function (domain-specific neurocognitive measure) | Assessed by Domain-specific neurocognitive measure. | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cerebral Vascular Reactivity