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Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer's disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion
Alvarez XA, Mouzo R, Pichel V, Pérez P, Laredo M, Fernández-Novoa L, Corzo L, Zas R et al.. Methods and findings in experimental and clinical pharmacology, 1999-11-01
Topic: Amyloid, tau and blood-test diagnosis
Citicoline has been extensively used for the treatment of neurodegenerative disorders associated with head trauma, stroke, brain aging, cerebrovascular pathology and Alzheimer's disease. In this study we have investigated the efficacy and safety of the treatment with citicoline versus placebo in patients with Alzheimer disease. As compared to placebo, citicoline improved cognitive performance in Alzheimer's disease patients with APOE E4 (ADAS: difference between groups = -3.2 +/- 1.8 scores, p < 0.05; ADAS-cog: difference between groups = -2.3 +/- 1.5, ns); and this improvement on cognition was more pronounced (ADAS, p < 0.01; ADAS-cog: difference between groups = -2.8 +/- 1.3, p < 0.06) in patients with mild dementia (GDS < 5). Significant differences with respect to placebo (p < 0.05) were observed for theta activity in several fronto-parieto-temporal electrodes of the left hemisphere. The present data indicate that citicoline (1,000 mg/day) is well tolerated and improves cognitive performance, cerebral blood perfusion and the brain bioelectrical activity pattern in AD patients. According to our results, it seems that citicoline might be a useful treatment in Alzheimer's disease, and that the efficacy of this compound is greater in patients with mild mental deterioration and/or bearing the epsilon 4 allele of the APOE.
Key findings
- Citicoline has been extensively used for the treatment of neurodegenerative disorders associated with head trauma, stroke, brain aging, cerebrovascular pathology and Alzheimer's disease.
- In this study we have investigated the efficacy and safety of the treatment with citicoline versus placebo in patients with Alzheimer disease.
- As compared to placebo, citicoline improved cognitive performance in Alzheimer's disease patients with APOE E4 (ADAS: difference between groups = -3.2 +/- 1.8 scores, p < 0.05; ADAS-cog: difference between groups = -2.3 +/- 1.5, ns); and this improvement on cognition was more pronounced (ADAS, p < 0.01; ADAS-cog: difference between groups = -2.8 +/- 1.3, p < 0.06) in patients with mild dementia (GDS < 5).
- Significant differences with respect to placebo (p < 0.05) were observed for theta activity in several fronto-parieto-temporal electrodes of the left hemisphere.
- The present data indicate that citicoline (1,000 mg/day) is well tolerated and improves cognitive performance, cerebral blood perfusion and the brain bioelectrical activity pattern in AD patients.
Why it matters
In this double-blind placebo-controlled study, citicoline improved cognitive performance in Alzheimer's disease patients who carried the APOE E4 allele, with more pronounced improvement in those with mild dementia. The study suggests citicoline might be useful, especially in certain patients, but it was a small trial and these findings need confirmation.
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Study details
- Participants17
- Evidence strengthHigh
How this study scored 54/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Methods and findings in experimental and clinical pharmacology) |
| Journal's citation record | 0 / 4 | Methods and Findings in Experimental and Clinical Pharmacology: journal h-index 59 (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 | 1999 — older than 20 years, still counted |
| Sample size | 1 / 4 | 17 participants |
| 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 (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 5 / 7 | Cited 140 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.8 citations a year over 29 year(s) since 1999 |
| Impact for its field and year | 2 / 6 | Cited 2.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 1 / 4 | Cited 11 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author et al: h-index 13 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | EuroEspes Biomedical Research Center: institution h-index 68 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 10669911) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 54 / 100 | — |
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May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
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
Alvarez, X. A., Mouzo, R., Pichel, V., Pérez, P., Laredo, M., Fernández-Novoa, L., et al. (1999). Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer's disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion. Methods and findings in experimental and clinical pharmacology. https://doi.org/10.1358/mf.1999.21.9.795632
Vancouver
Alvarez XA, Mouzo R, Pichel V, Pérez P, Laredo M, Fernández-Novoa L, et al. Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer's disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion. Methods and findings in experimental and clinical pharmacology. 1999. doi:10.1358/mf.1999.21.9.795632. PMID: 10669911.
BibTeX
@article{alvarez1999-10669911,
author = {Alvarez, X. A. and Mouzo, R. and Pichel, V. and Pérez, P. and Laredo, M. and Fernández-Novoa, L. and Corzo, L. and Zas, R. and others},
title = {{Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer's disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion}},
journal = {Methods and findings in experimental and clinical pharmacology},
year = {1999},
doi = {10.1358/mf.1999.21.9.795632},
pmid = {10669911},
url = {https://doi.org/10.1358/mf.1999.21.9.795632}
}
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