Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures

Arch Neurol. 2012 Jul;69(7):836-41. doi: 10.1001/archneurol.2012.85.

Abstract

Objective: To evaluate whether antioxidant supplements presumed to target specific cellular compartments affected cerebrospinal fluid (CSF) biomarkers.

Design: Double-blind, placebo-controlled clinical trial.

Setting: Academic medical centers.

Participants: Subjects with mild to moderate Alzheimer disease.

Intervention: 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.

Main outcome measures: 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.

Trial registration: clinicaltrials.gov Identifier: NCT00117403.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Activities of Daily Living
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / drug therapy*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Antioxidants / administration & dosage*
  • Ascorbic Acid / administration & dosage
  • Biomarkers / cerebrospinal fluid*
  • Cholinesterase Inhibitors / therapeutic use
  • Dietary Supplements*
  • Double-Blind Method
  • F2-Isoprostanes / cerebrospinal fluid
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Memantine / therapeutic use
  • Mental Status Schedule
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid
  • Retrospective Studies
  • Thioctic Acid / administration & dosage
  • Ubiquinone / administration & dosage
  • Ubiquinone / analogs & derivatives
  • alpha-Tocopherol / administration & dosage
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Biomarkers
  • Cholinesterase Inhibitors
  • F2-Isoprostanes
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Ubiquinone
  • Thioctic Acid
  • coenzyme Q10
  • alpha-Tocopherol
  • Ascorbic Acid
  • Memantine

Associated data

  • ClinicalTrials.gov/NCT00117403

Grant support