Date of Award
Doctor of Philosophy (PhD)
Computational and Data Sciences
Cyril Rakovski, Ph.D.
Seyed Ahmad Sajjadi, MD, Ph.D.
Adrian Vajiac, Ph.D.
Identifying optimal treatment options with respect to survival of Alzheimer's disease patients is crucially important and previously uninvestigated research question. Our objective was to estimate the causal effects of the most prevalent classes of Alzheimer’s disease drugs, Donepezil and Memantine, and their combined use on Survival and General Health Status Measures of Alzheimer's disease patients for the first five years after initial diagnosis. We carried out a thorough causal inference study using doubly robust estimators, nonparametric bootstrap confidence intervals, Bonferroni corrections for multiple comparisons and analyzing one of the largest high-quality medical databases containing millions of de-identified electronic health records obtained from over 110 health systems in the United States. We also analyzed demographic variables, preexisting conditions, and drug treatments. Our results show that the combined use of Donepezil and Memantine significantly increased the probability of three, four and five-year survival of AD patients, significantly decreases in the average number of hospital or emergency department visits per year, and significantly decreased the hospital length of stay. The adoption of the combined treatment of Memantine and Donepezil could extend the lives of approximately 174,000, 215,000 and 303,000 current Alzheimer's disease patients above the three, four and five-year survival thresholds since initial diagnosis that would have otherwise expired due to being presently treated with no drugs, the Memantine monotherapy, or the Donepezil monotherapy respectively. Switching the patients that are currently on no drug treatment or on Donepezil and Memantine monotherapies to the combined treatment of Donepezil and Memantine will decrease the total number of patient days in hospitals and emergency departments by over 1.47 million per year and lower the yearly medical expenses in the U.S. due to hospitalization of AD patients by over 984 million dollars.
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Firstinitial. Lastname, "Causal inference methods for estimation of survival and general health status measures of Alzheimer’s Disease patients," Ph.D. dissertation, Chapman University, Orange, CA, 2023. https://doi.org/10.36837/chapman.000495
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