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Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures
Galasko DR, Peskind E, Clark CM, Quinn JF, Ringman JM, Jicha GA, Cotman C, Cottrell B et al.. Archives of neurology, 2012-07-01
Topic: Amyloid, tau and blood-test diagnosis
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.
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APA 7th
Galasko, D. R., Peskind, E., Clark, C. M., Quinn, J. F., Ringman, J. M., Jicha, G. A., et al. (2012). Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Archives of neurology. https://doi.org/10.1001/archneurol.2012.85
Vancouver
Galasko DR, Peskind E, Clark CM, Quinn JF, Ringman JM, Jicha GA, et al. Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Archives of neurology. 2012. doi:10.1001/archneurol.2012.85. PMID: 22431837.
BibTeX
@article{galasko2012-22431837,
author = {Galasko, D. R. and Peskind, E. and Clark, C. M. and Quinn, J. F. and Ringman, J. M. and Jicha, G. A. and Cotman, C. and Cottrell, B. and others},
title = {{Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures}},
journal = {Archives of neurology},
year = {2012},
doi = {10.1001/archneurol.2012.85},
pmid = {22431837},
url = {https://doi.org/10.1001/archneurol.2012.85}
}
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Key findings
- Results Seventy-eight subjects were randomized; 66 provided serial CSF specimens adequate for biochemical analyses.
Why it matters
Antioxidant supplements did not influence cerebrospinal fluid biomarkers related to amyloid or tau, and there was accelerated decline in Mini-Mental State Examination scores in the vitamin E, vitamin C, and alpha-lipoic acid group, a potential safety concern. The study was small, with 78 subjects randomized and 66 providing adequate spinal fluid samples.
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Study details
- Evidence strengthHigh
How this study scored 72/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for sample size and effect reported because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 69 of the 96 points we could judge it on, which is 72 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of neurology) |
| Journal's citation record | 3 / 4 | Archives of Neurology: journal h-index 353 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2012 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 6 / 7 | Cited 378 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 23.6 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 4 / 6 | Cited 19.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 14 other studies in this library |
| Still being cited | 3 / 4 | Cited 53 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author for the Alzheimer's Disease Cooperative Study holds only 1 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22431837) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 69 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 69 of the 96 points we could judge it on is 72 out of 100. |
| Total | 72 / 100 | — |
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