Antioxidants for Alzheimer Disease

Arch Neurol. 2012 Mar 19. [Epub ahead of print]

Antioxidants for Alzheimer Disease: A Randomized Clinical Trial With Cerebrospinal Fluid Biomarker Measures.

Source

University of California, San Diego (Drs Galasko, Thomas, and Aisen and Ms Cottrell), Mary S. Easton Center for Alzheimer’s Disease Research, Department of Neurology, University of California, Los Angeles (Dr Ringman), and Department of Neurobiology, University of California, Irvine (Dr Cotman); Department of Psychiatry, University of Washington, and Seattle VA Medical Center, Seattle (Drs Peskind and Montine); Avid Radiopharmaceuticals, Inc, Philadelphia, Pennsylvania (Dr Clark); Department of Neurology, Oregon Health and Sciences University, Portland (Dr Quinn); and Department of Neurology, University of Kentucky, Lexington (Dr Jicha).

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.

Citation