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Memantine in moderate-to-severe Alzheimer's disease
Reisberg B, Doody R, Stöffler A, Schmitt F, Ferris S, Möbius HJ, Memantine Study Group.. The New England journal of medicine, 2003-04-01
Topic: Amyloid, tau and blood-test diagnosis
Background Overstimulation of the N-methyl-D-aspartate (NMDA) receptor by glutamate is implicated in neurodegenerative disorders. Accordingly, we investigated memantine, an NMDA antagonist, for the treatment of Alzheimer's disease. Methods Patients with moderate-to-severe Alzheimer's disease were randomly assigned to receive placebo or 20 mg of memantine daily for 28 weeks. The primary efficacy variables were the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus) and the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory modified for severe dementia (ADCS-ADLsev). The secondary efficacy end points included the Severe Impairment Battery and other measures of cognition, function, and behavior. Treatment differences between base line and the end point were assessed. Missing observations were imputed by using the most recent previous observation (the last observation carried forward). The results were also analyzed with only the observed values included, without replacing the missing values (observed-cases analysis). Results Two hundred fifty-two patients (67 percent women; mean age, 76 years) from 32 U.S. centers were enrolled. Of these, 181 (72 percent) completed the study and were evaluated at week 28. Seventy-one patients discontinued treatment prematurely (42 taking placebo and 29 taking memantine). Patients receiving memantine had a better outcome than those receiving placebo, according to the results of the CIBIC-Plus (P=0.06 with the last observation carried forward, P=0.03 for observed cases), the ADCS-ADLsev (P=0.02 with the last observation carried forward, P=0.003 for observed cases), and the Severe Impairment Battery (P Conclusions Antiglutamatergic treatment reduced clinical deterioration in moderate-to-severe Alzheimer's disease, a phase associated with distress for patients and burden on caregivers, for which other treatments are not available.
Key findings
- The results were also analyzed with only the observed values included, without replacing the missing values (observed-cases analysis).
- Results Two hundred fifty-two patients (67 percent women; mean age, 76 years) from 32 U.S. centers were enrolled.
- Patients receiving memantine had a better outcome than those receiving placebo, according to the results of the CIBIC-Plus (P=0.06 with the last observation carried forward, P=0.03 for observed cases), the ADCS-ADLsev (P=0.02 with the last observation carried forward, P=0.003 for observed cases), and the Severe Impairment Battery (P<0.001 with the last observation carried forward, P=0.002 for observed cases).
Why it matters
In a 28-week trial, patients with moderate-to-severe Alzheimer's taking memantine had better outcomes on some measures of daily living and overall change than those taking placebo. This suggests memantine may help with symptoms in later stages, but it does not cure or prevent the disease.
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Study details
- Evidence strengthLow
How this study scored 63/100
Published in a top-tier journal. Scored zero for study design, sample size and effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (The New England journal of medicine) |
| Journal's citation record | 4 / 4 | New England Journal of Medicine: journal h-index 1,505 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2003 — older than 20 years, still counted |
| 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 | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 7 / 7 | Cited 2,039 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 81.6 citations a year over 25 year(s) since 2003 |
| Impact for its field and year | 6 / 6 | Cited 83.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 54 other studies in this library |
| Still being cited | 4 / 4 | Cited 241 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Hans Jörg Möbius: h-index 15 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | New York University: institution h-index 1,612 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12672860) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 63 / 100 | — |
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Read the original
- DOI: 10.1056/nejmoa013128
- PubMed: 12672860
- Original source →
- Free full text: New England Journal of Medicine →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Reisberg, B., Doody, R., Stöffler, A., Schmitt, F., Ferris, S., Möbius, H. J., et al. (2003). Memantine in moderate-to-severe Alzheimer's disease. The New England journal of medicine. https://doi.org/10.1056/nejmoa013128
Vancouver
Reisberg B, Doody R, Stöffler A, Schmitt F, Ferris S, Möbius HJ, et al. Memantine in moderate-to-severe Alzheimer's disease. The New England journal of medicine. 2003. doi:10.1056/nejmoa013128. PMID: 12672860.
BibTeX
@article{reisberg2003-12672860,
author = {Reisberg, B. and Doody, R. and Stöffler, A. and Schmitt, F. and Ferris, S. and Möbius, H. J. and {Memantine Study Group}},
title = {{Memantine in moderate-to-severe Alzheimer's disease}},
journal = {The New England journal of medicine},
year = {2003},
doi = {10.1056/nejmoa013128},
pmid = {12672860},
url = {https://doi.org/10.1056/nejmoa013128}
}
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