Title: Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures.
Authors: Galasko, Douglas R; Peskind, Elaine; Clark, Christopher M; Quinn, Joseph F; Ringman, John M; Jicha, Gregory A; Cotman, Carl; Cottrell, Barbara; Montine, Thomas J; Thomas, Ronald G; Aisen, Paul; Alzheimer’s Disease Cooperative Study
Published In Arch Neurol, (2012 Jul)
Abstract: To evaluate whether antioxidant supplements presumed to target specific cellular compartments affected cerebrospinal fluid (CSF) biomarkers.Double-blind, placebo-controlled clinical trial.Academic medical centers.Subjects with mild to moderate Alzheimer disease.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.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).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.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.clinicaltrials.gov Identifier: NCT00117403.
PubMed ID: 22431837
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