期刊
ARCHIVES OF NEUROLOGY
卷 69, 期 7, 页码 836-841出版社
AMER MEDICAL ASSOC
DOI: 10.1001/archneurol.2012.85
关键词
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资金
- National Institutes of Health (NIH) [P50AGO5131, U01 AG10483]
- Eli Lilly
- Bristol-Myers Squibb
- Novartis
- NIH [R01 AGO33133, P50AGO0817, U01AG10483, P30AG028383, R01AG019241, U01 AG010483, R01 HD064993-0110, L30AG032934, AR47752, AG000096, AG00538, AG016573, P50 NS62684, R01 ES16754, T32 ES07032, R01 AG31892, U01 AG32984, P50 AGO5136, R01 AG16381]
- Department of Veterans Affairs (VA Cooperative Study) [563]
- Rehabilitation Research and Development Merit Review)
- Department of Veterans Affairs (merit review funding)
- National Institute on Aging (NIA) [P50AG16570, U01AG032438, UO1 AG10483]
- Janssen
- Baxter
- Pfizer
- Medivation
- Danone
- Alzheimer's Association [NIRG-07-59967]
- Pfizer Inc
- Baxter International Inc
- NIH NIA [U01 AG10483, U01 AG024904, R01 AG030048]
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 (alpha-tocopherol) plus 500 mg/d of vitamin C plus 900 mg/d of alpha-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 A beta 42, 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.
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