Effects of Simvastatin on Biomarkers

Inclusion Criteria (participants must meet the following criteria) * If female of childbearing potential, must have negative pregnancy test at baseline, and all subsequent visits. * Age 45 to 64 years inclusive. * Considered cognitively normal with no evidence of memory or other cognitive impairments (MMSE \>26, Logical Memory delayed recall \> 6, CDR score of 0). * Normal or only mildly elevated cholesterol which does not require drug therapy based on National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP-III) guidelines. * An LDL level above 70mg/dL. * Hamilton Depression Scale (HAM-D) score \< 12. * BMI between 18 - 34 (or exception made by MD). * In good recent general health (i.e., no trauma or infection in the 4 weeks before LP). * On stable dose of non-exclusionary medications for the 4 weeks preceding the LP. * Platelet count \>100,000. Exclusion Criteria (participants must NOT satisfy any of the following conditions) * Any contraindications to LP, such as spinal deformity, severe disease or infection in the LP region, bleeding tendency, anticoagulant or blood-thinning medications. * Taken a statin medication in the past 12 months. * Any clinically significant laboratory abnormalities. * Any neurological disorders: multiple sclerosis, epilepsy, stroke, Parkinson's, other degenerative CNS disorders, or neuropathy with radicular involvement. * Acute or chronic major psychiatric disorders: schizophrenia, affective disorders, or severe anxiety disorders. (Dysthymia allowed, history of MDD allowed if currently in remission) * Unstable or poorly controlled medical problems such as: heart failure, diabetes (poorly controlled or insulin dependent), hypertension (BP \>160/100), pulmonary disease with hypoxia or hypercapnia, significant liver disease or known hepatitis C seropositivity, renal failure, treatment for cancer in the past 2 years (other than non-melanoma skin cancer) or known HIV positive status. * Use of illegal drugs or alcohol abuse (\>2 drinks/day or 10/week) within the past year. * Concurrent participation in another investigational drug study. * Use of any exclusionary medications in the 4 weeks prior to screening: * Drugs which could interact with statins: itraconazole, ketoconazole, erythromycin, clarithromycin, HIV protease inhibitors, nefazodone, amiodarone, cyclosporine, isoniazid, quinidine, or large quantities of grapefruit juice (\>1 quart daily) * Central nervous system acting medications: antipsychotics, anti-Parkinson's disease medications, anti convulsants, or CNS stimulants * Chronic use of benzodiazepines, sedating antihistamines, or other sedative-hypnotic agents (prn use is allowed as long as it is not within 72 hours of LP or cognitive testing) * Medications affecting coagulation and/or inflammation: coumadin, potent anti-inflammatory medications (hydrocortisone, methotrexate or other potent immune-modulating medications), and anti-HIV medications (Aspirin up to 325 mg/day is allowed.) * Lipid-lowering drugs: fibrates or niacin \>500mg/day (stable dose of omega-3 is allowed) * Does the subject's family history meet any of the following criteria? * Both parents had/have dementia * On one side of the family, over two consecutive generations three relatives had/have dementia? * One parent had an onset of dementia before age 60? * Does the subject have a major active autoimmune or immunological disorder?