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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.
Alzheimer’s disease is the most common type of dementia, affecting millions of people worldwide. In this study, we investigated the effects of two drugs commonly prescribed to people with Alzheimer’s disease called Donepezil and Memantine to see whether they had an impact on when people died. We found that the combined use of Donepezil and Memantine significantly increased the probability of a person surviving five years compared to no drug treatment or treatment with Donepezil or Memantine alone. Our results suggest that the lives of many Alzheimer’s patients in the USA who are currently on no drug treatment or just Donepezil or Memantine could be extended if they were treated with both drugs simultaneously.
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