Long-term effects of the concomitant use of memantine with cholinesterase inhibition in Alzheimer disease
Open accessAbstract
BACKGROUND: Patients using cholinesterase inhibitors (ChEIs) have a delay in nursing home (NH) admission compared with those who were not using the medication. There are no long-term studies of the effects of memantine in combination with ChEIs use in Alzheimer disease (AD). This study was conducted to examine the effects of ChEIs and memantine on time to death and time to NH admission. METHODS: Time to NH admission and death was examined in 943 probable AD patients who had at least a 1-year follow-up evaluation. Of these patients, 140 (14.9%) used both ChEIs and memantine, 387 (41%) [corrected] used only ChEIs, and 416 (44.1%) [corrected] used neither. The mean (SD) follow-up time was 62.3 (35.8) months. The analysis was conducted with multivariable Cox proportional hazard models controlling for critical covariates (ie, age, education level, gender, severity of the dementia, hypertension, diabetes mellitus, heart disease, psychiatric symptoms and use of psychotropic medications). RESULTS: Compared with those who never used cognitive enhancers, patients who used ChEIs had a significant delay in NH admission (HR: 0.37, 95% CI 0.27 to 0.49); this effect was significantly augmented with the addition of memantine (HR: 0.29, 95% CI 0.11 to 0.72) (memantine+ChEI vs ChEI alone). ChEIs alone, or in combination with memantine had no significant association on time to death. CONCLUSIONS: This observational study revealed that the addition of the NMDA receptor antagonist memantine to the treatment of AD with ChEI significantly altered the treated history of AD by extending time to nursing home admission.
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Short-term randomized controlled trials, longer-term open-label extensions, and long-term observational prospective clinical cohort effectiveness studies support the safety and benefits of anti-AD treatments in combination, most frequently as memantine added on to a stable regimen of background cholinesterase inhibitor treatment.
“Short-term (6-12 months) RCTs (level I evidence), longer-term (12-36 months) openlabel extensions of RCTs (level II or III evidence), and long-term (2 to 5-plus years) observational prospective clinical cohort effectiveness studies (level II evidence) support the safety and benefits of anti-AD treatments in combination, most frequently as memantine added on to a stable regimen of background ChEI”
From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [117]
Longer-term prospective observational clinical patient cohort studies report reduced clinical decline in patients with AD treated at any stage.
“Longer-term prospective observational clinical patient cohort studies report reduced clinical decline in patients with AD treated at any stage.[114][115][116][117][118][119]”
From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [117]
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- Authors
- Lopez, O. L., Becker, J. T., Wahed, A. S., Saxton, J., Sweet, R. A., Wolk, D. A., Klunk, W., & DeKosky, S. T.
- Affiliations
- University of Pittsburgh (US)
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2009-02-09
- Volume
- 80
- Issue
- 6
- Pages
- 600-607
- ISSN
- 0022-3050 (ISSN-L)
- PMC
- PMC2823571
- OpenAlex
- W2171545307
- Cited by
- 266
- References
- 56
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 10 · 2023: 5 · 2022: 9 · 2021: 5 · 2020: 11 · 2019: 7 · 2018: 14 · 2017: 14 · 2016: 18 · 2015: 26 · 2014: 18 · 2013: 25 · 2012: 30
- FWCI
- 18.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health (5p01ag003705-04)
- National Institute on Aging (AG 05-133, AG 20098, AG027224, P50AG005133, U01AG016976, AG 03705, R01AG020098, AG-16976, R56AG020098, R01AG027224)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, memantine, cholinesterase inhibitors, combination therapy, nursing home admission, time to death, NMDA receptor antagonists, long-term effects
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cholinesterase Inhibitors, Drug Therapy, Combination, Female, Follow-Up Studies, Homes for the Aged, Humans, Male, Memantine, Mental Status Schedule, Neuropsychological Tests, Nursing Homes, Patient Admission, Survival Analysis, Excitatory Amino Acid Antagonists, Nootropic Agents
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