RT Journal
A1 Galasko DR, Peskind E, Clark CM, et al
T1 Antioxidants for alzheimer disease: A randomized clinical trial with cerebrospinal fluid biomarker measures
JF Archives of Neurology
JO Archives of Neurology
YR 2012
FD July 1
VO 69
IS 7
SP 836
OP 841
DO 10.1001/archneurol.2012.85
UL http://dx.doi.org/10.1001/archneurol.2012.85
AB 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-tau181 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