Do HMG CoA Reductase Inhibitors Affect Abeta Levels?

• Status: Completed
• Trial end date: 2005-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Recent evidence suggests that there is a significant overlap between AD and cerebrovascular disease. In fact, AD and cerebrovascular disease may share some of the same risk factors, including hypercholesterolemia. In addition, studies have suggested that the HMG Co-A reductase inhibitor lipid-lowering agents, known as "statins," decrease the risk of AD by up to 70%; however, effects differed by specific statin use. This study will compare two statins, simvastatin (which crosses the blood brain barrier) and pravastatin (which does not), with respect to their ability to alter blood and cerebrospinal fluid (CSF) levels of AD and inflammatory markers. The primary aim of the proposed study is to determine whether there is a reduction in Abeta with statins and whether the ability of the statin to cross the blood-brain barrier will affect its ability to decrease Abeta. If it can be demonstrated that statins alter AD-associated biomarkers, this would have broad implications for the treatment and prevention of AD.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Seattle Institute for Biomedical and Clinical Research
• Treatments: Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pravastatin; Simvastatin

Criteria

Inclusion Criteria:

• Total cholesterol > 200, and/or LDL > 130

• No cognitive impairment

• Statin-naive for at least one year

• Women must not be pregnant, nursing, or planning to become pregnant

Exclusion Criteria:

• Back ailments which would hinder LP procedure

• Neurological disease, including stroke, Parkinson's disease, Multiple Sclerosis, uncontrolled epilepsy, history of severe head trauma

• Hepatic disease

• Renal insufficiency

• Unstable medical disease

• Severe pulmonary disease

• Severe cardiac disease

• Uncontrolled hypertension (greater than 160/90)

• Uncontrolled hyper/hypothyroidism

• History of blood clotting abnormalities or platelet abnormalities

• History of chronic major psychiatric disorders or presence of current major depressive disorder (by DSM-IV criteria)

• History of substance abuse within the past year

• Taking exclusionary medications