title: Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures.
abstract: OBJECTIVE
  To evaluate whether antioxidant supplements presumed to target specific cellular compartments affected cerebrospinal fluid (CSF) biomarkers.
  
  
  METHODS
  Double-blind, placebo-controlled clinical trial.
  
  
  METHODS
  Academic medical centers.
  
  
  METHODS
  Subjects with mild to moderate Alzheimer disease.
  
  
  METHODS
  Random assignment to treatment for 16 weeks with 800 IU/d of vitamin E (α-tocopherol) plus 500 mg/d of vitamin C plus 900 mg/d of α-lipoic acid (E/C/ALA); 400 mg of coenzyme Q 3 times/d; or placebo.
  
  
  METHODS
  Changes from baseline to 16 weeks in CSF biomarkers related to Alzheimer disease and oxidative stress, cognition (Mini-Mental State Examination), and function (Alzheimer's Disease Cooperative Study Activities of Daily Living Scale).
  
  
  RESULTS
  Seventy-eight subjects were randomized; 66 provided serial CSF specimens adequate for biochemical analyses. Study drugs were well tolerated, but accelerated decline in Mini-Mental State Examination scores occurred in the E/C/ALA group, a potential safety concern. Changes in CSF Aβ42, tau, and P-tau(181) levels did not differ between the 3 groups. Cerebrospinal fluid F2-isoprostane levels, an oxidative stress biomarker, decreased on average by 19% from baseline to week 16 in the E/C/ALA group but were unchanged in the other groups.
  
  
  CONCLUSIONS
  Antioxidants did not influence CSF biomarkers related to amyloid or tau pathology. Lowering of CSF F2-isoprostane levels in the E/C/ALA group suggests reduction of oxidative stress in the brain. However, this treatment raised the caution of faster cognitive decline, which would need careful assessment if longer-term clinical trials are conducted.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00117403.
authors.affiliation: Department of Neurosciences, University of California, San Diego, 92093, USA. dgalasko@ucsd.edu
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Galasko
authors.forename: Elaine
authors.initials: E
authors.lastname: Peskind
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Clark
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Quinn
authors.forename: John M
authors.initials: JM
authors.lastname: Ringman
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Jicha
authors.forename: Carl
authors.initials: C
authors.lastname: Cotman
authors.forename: Barbara
authors.initials: B
authors.lastname: Cottrell
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Thomas
authors.forename: Paul
authors.initials: P
authors.lastname: Aisen
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D000975:Antioxidants / Q000008:administration & dosage*; D001205:Ascorbic Acid / Q000008:administration & dosage; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D019587:Dietary Supplements; D004311:Double-Blind Method; D028441:F2-Isoprostanes / Q000134:cerebrospinal fluid; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008559:Memantine / Q000627:therapeutic use; D008609:Mental Status Schedule; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D012189:Retrospective Studies; D008063:Thioctic Acid / Q000008:administration & dosage; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives; D024502:alpha-Tocopherol / Q000008:administration & dosage; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D015415:Biomarkers; D002800:Cholinesterase Inhibitors; D028441:F2-Isoprostanes; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D014451:Ubiquinone; D008063:Thioctic Acid; C024989:coenzyme Q10; D024502:alpha-Tocopherol; D001205:Ascorbic Acid; D008559:Memantine