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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.

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.

Links

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  • Authors+Show Affiliations

    ,

    Department of Neurosciences, University of California, San Diego, 92093, USA. dgalasko@ucsd.edu

    , , , , , , , , , ,

    Source

    Archives of neurology 69:7 2012 Jul pg 836-41

    MeSH

    Activities of Daily Living
    Aged
    Aged, 80 and over
    Alzheimer Disease
    Amyloid beta-Peptides
    Antioxidants
    Ascorbic Acid
    Biological Markers
    Cholinesterase Inhibitors
    Dietary Supplements
    Double-Blind Method
    F2-Isoprostanes
    Female
    Follow-Up Studies
    Humans
    Male
    Memantine
    Mental Status Schedule
    Middle Aged
    Peptide Fragments
    Retrospective Studies
    Thioctic Acid
    Ubiquinone
    alpha-Tocopherol
    tau Proteins

    Pub Type(s)

    Journal Article
    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.

    Language

    eng

    PubMed ID

    22431837

    Citation

    TY - JOUR T1 - Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. AU - Galasko,Douglas R, AU - Peskind,Elaine, AU - Clark,Christopher M, AU - Quinn,Joseph F, AU - Ringman,John M, AU - Jicha,Gregory A, AU - Cotman,Carl, AU - Cottrell,Barbara, AU - Montine,Thomas J, AU - Thomas,Ronald G, AU - Aisen,Paul, AU - ,, PY - 2012/3/21/entrez PY - 2012/3/21/pubmed PY - 2012/12/10/medline SP - 836 EP - 41 JF - Archives of neurology JO - Arch. Neurol. VL - 69 IS - 7 N2 - 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. SN - 1538-3687 UR - https://www.unboundmedicine.com/medline/citation/22431837/full_citation L2 - http://archneur.jamanetwork.com/article.aspx?doi=10.1001/archneurol.2012.85 ER -