Combined Use of Donepezil and Memantine Increases the Probability of Five-Year Survival of Alzheimer’s Disease Patients

Authors

Ehsan Yaghmaei, Chapman UniversityFollow
Hongxia Lu, University of North Carolina at Chapel Hill
Louis Ehwerhemuepha, Children’s Hospital of Orange County
Jianwei Zheng, Chapman UniversityFollow
Sidy Danioko, Chapman UniversityFollow
Ahmad Rezaie, Chapman University
Seyed Ahmad Sajjadi, University of California, Irvine
Cyril Rakovski, Chapman UniversityFollow

Document Type

Article

Publication Date

5-23-2024

Abstract

Background

Alzheimer’s disease (AD) is the most common neurodegenerative disease. Studying the effects of drug treatments on multiple health outcomes related to AD could be beneficial in demonstrating which drugs reduce the disease burden and increase survival.

Methods

We conducted a comprehensive causal inference study implementing doubly robust estimators and using one of the largest high-quality medical databases, the Oracle Electronic Health Records (EHR) Real-World Data. Our work was focused on the estimation of the effects of the two common Alzheimer’s disease drugs, Donepezil and Memantine, and their combined use on the five-year survival since initial diagnosis of AD patients. Also, we formally tested for the presence of interaction between these drugs.

Results

Here, we show that the combined use of Donepezil and Memantine significantly elevates the probability of five-year survival. In particular, their combined use increases the probability of five-year survival by 0.050 (0.021, 0.078) (6.4%), 0.049 (0.012, 0.085), (6.3%), 0.065 (0.035, 0.095) (8.3%) compared to no drug treatment, the Memantine monotherapy, and the Donepezil monotherapy respectively. We also identify a significant beneficial additive drug-drug interaction effect between Donepezil and Memantine of 0.064 (0.030, 0.098).

Conclusions

Based on our findings, adopting combined treatment of Memantine and Donepezil could extend the lives of approximately 303,000 people with AD living in the USA to be beyond five-years from diagnosis. If these patients instead have no drug treatment, Memantine monotherapy or Donepezil monotherapy they would be expected to die within five years.

Comments

This article was originally published in Communications Medicine, volume 4, in 2024. https://doi.org/10.1038/s43856-024-00527-6

Recommended Citation

Yaghmaei, E., Lu, H., Ehwerhemuepha, L. et al. Combined use of Donepezil and Memantine increases the probability of five-year survival of Alzheimer’s disease patients. Commun Med 4, 99 (2024). https://doi.org/10.1038/s43856-024-00527-6

Peer Reviewed

1

Copyright

The authors

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.