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Cumulative, additive benefits of memantine-donepezil combination over component monotherapies in moderate to severe Alzheimer’s dementia: a pooled area under the curve analysis

Overview of attention for article published in Alzheimer's Research & Therapy, May 2015
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (85th percentile)

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Title
Cumulative, additive benefits of memantine-donepezil combination over component monotherapies in moderate to severe Alzheimer’s dementia: a pooled area under the curve analysis
Published in
Alzheimer's Research & Therapy, May 2015
DOI 10.1186/s13195-015-0109-2
Pubmed ID
Authors

Alireza Atri, Suzanne B Hendrix, Vojislav Pejović, Robert K Hofbauer, John Edwards, José Luis Molinuevo, Stephen M Graham

Abstract

Treatment in moderate or severe Alzheimer's disease (AD) often involves adding memantine to a cholinesterase-inhibitor (ChEI: donepezil, galantamine, rivastigmine). Evidence from six-month randomized trials and long-term observational studies supports superiority of memantine-ChEI combination to ChEI monotherapy. We utilized area-under-the-curve (AUC) analysis to assess six-month cumulative treatment efficacy of memantine-donepezil combination versus component monotherapies on individual clinical domains and on a composite index. Data were pooled from 1,408 individuals with moderate to severe AD from four six-month randomized trials of memantine monotherapy (n = 570) or add-on therapy (donepezil-only subset: n = 847). AUC changes from baseline on measures of cognition (SIB), function (ADCS-ADL19), behavior (NPI), global status (CIBIC-Plus), and a composite index (4D-CI: equally weighted composite of four domain measures) were calculated using the trapezoidal rule and evaluated via analysis of covariance (ANCOVA) (2-sided-α = 0.05). AUC results were contrasted with visit-by-visit changes from baseline ("snapshot analysis"), performed using a mixed-effects model with repeated measures (MMRM). Over the entire six-month period, placebo-only treatment was associated with significant cumulative worsening on all outcomes. Memantine-donepezil combination showed significantly greater AUC improvements (point x week) on the SIB, NPI, and CIBIC-Plus than placebo-donepezil (SIB: 68.4 versus 32.0, P = 0.019; NPI: -74.3 versus -28.2, P = 0.003; CIBIC-Plus: -2.5 versus 1.4, P = 0.006) and memantine-only monotherapies (SIB: 68.4 versus 12.0, P <0.001; NPI: -74.3 versus -7.4, P <0.001; CIBIC-Plus: -2.5 versus 2.7, P <0.001), whereas these comparisons were not significant for the ADCS-ADL19 (memantine-donepezil (1.4) versus placebo-donepezil (-0.9), P = 0.407; versus memantine-only (-12.2), P = 0.310). Composite index analysis demonstrated significant cumulative advantages of memantine-donepezil combination (630.0) over placebo-donepezil (344.7, P <0.001) and memantine-only (152.1, P <0.001) treatments. Combining memantine and donepezil had an additive effect. Compared with AUC analysis, baseline-to-endpoint change-score analysis underestimated effects of combination therapy, monotherapies, or both. This large pooled area-under-the-curve analysis of randomized-trial data in moderate to severe AD provides ecologically valid support that adding memantine to stable donepezil results in overall clinical benefits that are additive compared with individual monotherapies, continue to accumulate through six-month treatment, and are at least 50% greater than those of monotherapies.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 98 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 1%
Unknown 97 99%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 13%
Student > Master 12 12%
Other 11 11%
Student > Bachelor 11 11%
Student > Postgraduate 9 9%
Other 17 17%
Unknown 25 26%
Readers by discipline Count As %
Medicine and Dentistry 22 22%
Pharmacology, Toxicology and Pharmaceutical Science 13 13%
Neuroscience 9 9%
Biochemistry, Genetics and Molecular Biology 6 6%
Agricultural and Biological Sciences 5 5%
Other 12 12%
Unknown 31 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 11. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 February 2019.
All research outputs
#2,970,996
of 24,378,498 outputs
Outputs from Alzheimer's Research & Therapy
#704
of 1,355 outputs
Outputs of similar age
#37,439
of 269,652 outputs
Outputs of similar age from Alzheimer's Research & Therapy
#15
of 23 outputs
Altmetric has tracked 24,378,498 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,355 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 26.2. This one is in the 46th percentile – i.e., 46% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 269,652 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 85% of its contemporaries.
We're also able to compare this research output to 23 others from the same source and published within six weeks on either side of this one. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.