Chronic divalproex sodium use and brain atrophy in Alzheimer disease
Fleisher AS, Truran D, Mai JT, Langbaum JB, Aisen PS, Cummings JL, Jack CR, Weiner MW et al.. Neurology, 2011-09-14
Topic: Amyloid, tau and blood-test diagnosis
Objective We evaluated the effect of the divalproex sodium formulation of valproic acid on brain volumes using MRI in people with mild to moderate Alzheimer disease (AD) and assessed for changes associated with behavioral and cognitive effects. Methods Eighty-nine of 313 participants randomized to divalproex or placebo in a 24-month, parallel-group trial received MRI scans at baseline and 12 months. Interval MRI annual percent changes in whole brain, ventricular, and hippocampal volumes were the primary outcomes of interest. Change from baseline in clinical outcomes was assessed at 6-month intervals. Results There were no baseline differences between active treatment and placebo groups in age, education, brain volumes, clinical rating scores, or APOE ε4 carrier status. The group treated with divalproex showed a greater rate of decline in left and right hippocampal and brain volumes (-10.9% and -12.4% vs -5.6% and -6.3%, and -3.5% vs -1.4%, respectively), and a greater rate of ventricular expansion (24.5% vs 9.9%) (p Conclusions Divalproex treatment was associated with accelerated brain volume loss over 1 year and perhaps with greater cognitive impairment. The long-term clinical effects of these changes are not known.
Key findings
- Objective We evaluated the effect of the divalproex sodium formulation of valproic acid on brain volumes using MRI in people with mild to moderate Alzheimer disease (AD) and assessed for changes associated with behavioral and cognitive effects.
- Results There were no baseline differences between active treatment and placebo groups in age, education, brain volumes, clinical rating scores, or APOE ε4 carrier status.
- The group treated with divalproex showed a greater rate of decline in left and right hippocampal and brain volumes (-10.9% and -12.4% vs -5.6% and -6.3%, and -3.5% vs -1.4%, respectively), and a greater rate of ventricular expansion (24.5% vs 9.9%) (p < 0.001).
Why it matters
In people with mild to moderate Alzheimer's disease, treatment with divalproex sodium was linked to faster loss of hippocampal and whole brain volume and greater ventricular expansion over one year compared with placebo. The long-term clinical effects of these brain volume changes are not known.
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Study details
- Participants313
- Effect size10.9%; 12.4%; 5.6%
- Evidence strengthHigh
How this study scored 72/100
Published in a leading specialty journal, and it is a randomised controlled trial. 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 | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (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 | 2011 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 313 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 5 / 7 | Cited 178 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.5 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 3 / 6 | Cited 7.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 2 / 4 | Cited 25 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21917762) |
| 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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Read the original
- DOI: 10.1212/wnl.0b013e318230a16c
- PubMed: 21917762
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Fleisher, A. S., Truran, D., Mai, J. T., Langbaum, J. B., Aisen, P. S., Cummings, J. L., et al. (2011). Chronic divalproex sodium use and brain atrophy in Alzheimer disease. Neurology. https://doi.org/10.1212/wnl.0b013e318230a16c
Vancouver
Fleisher AS, Truran D, Mai JT, Langbaum JB, Aisen PS, Cummings JL, et al. Chronic divalproex sodium use and brain atrophy in Alzheimer disease. Neurology. 2011. doi:10.1212/wnl.0b013e318230a16c. PMID: 21917762.
BibTeX
@article{fleisher2011-21917762,
author = {Fleisher, A. S. and Truran, D. and Mai, J. T. and Langbaum, J. B. and Aisen, P. S. and Cummings, J. L. and Jack, C. R. and Weiner, M. W. and others},
title = {{Chronic divalproex sodium use and brain atrophy in Alzheimer disease}},
journal = {Neurology},
year = {2011},
doi = {10.1212/wnl.0b013e318230a16c},
pmid = {21917762},
url = {https://doi.org/10.1212/wnl.0b013e318230a16c}
}
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