Combining Alzheimer’s drugs extends patients’ lives, study finds

New research provides evidence that using two common Alzheimer’s disease medications together can significantly increase patients’ chances of surviving beyond five years from diagnosis. The study, published in Communications Medicine, suggests that this combined treatment could extend the lives of approximately 303,000 people with Alzheimer’s disease in the United States.

Alzheimer’s disease is the most common form of dementia, characterized by progressive memory loss, cognitive decline, and behavioral changes. It affects over 50 million people worldwide and is a leading cause of death. Alzheimer’s disease primarily impacts older adults, with the risk increasing significantly after age 65. The disease progresses through various stages, starting with mild memory problems and advancing to severe cognitive impairment, loss of ability to perform daily activities, and ultimately, death.

Despite extensive research, the exact causes of Alzheimer’s are not fully understood, but it is believed to involve a combination of genetic, environmental, and lifestyle factors. Key pathological features include the buildup of amyloid plaques and tau tangles in the brain, which disrupt neuronal communication and lead to cell death. Current treatments for Alzheimer’s disease are limited. Most available medications focus on alleviating symptoms rather than stopping or reversing disease progression.

Given the rising prevalence of Alzheimer’s disease and the limited effectiveness of current treatments, there is a pressing need for new therapeutic strategies that can enhance patient outcomes and survival. The new study was conducted to explore whether combining two existing drugs, Donepezil and Memantine, could offer a more effective treatment approach.

Previous research had suggested that these drugs might have complementary mechanisms of action, potentially providing greater benefits when used together. Donepezil, a cholinesterase inhibitor, helps increase levels of acetylcholine in the brain, which can enhance communication between nerve cells and improve cognitive function. Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, helps regulate the activity of glutamate, a neurotransmitter involved in learning and memory.

For their study, the researchers used data from the Oracle Electronic Health Records Real-World Data, a comprehensive medical database encompassing over 100 million patients from more than 110 health systems in the United States. The study focused on a cohort of 12,744 Alzheimer’s patients diagnosed in 2016, ensuring a five-year follow-up period.

The sample included patients diagnosed with Alzheimer’s disease who were treated with either Donepezil, Memantine, a combination of both, or no drug treatment at all. Patients who switched treatments during the study period were excluded to ensure consistency in treatment analysis. The researchers used advanced statistical methods, including doubly robust estimators and nonparametric bootstrapping, to account for potential biases and accurately estimate the effects of the treatments on five-year survival rates.

The study found that the combined use of Donepezil and Memantine significantly increased the probability of surviving five years after an Alzheimer’s diagnosis compared to no treatment or single-drug treatments. Specifically, the combined treatment group had a five-year survival probability of 83%, while the no-treatment group had a survival probability of 78%. Patients treated with Donepezil alone had a 76.5% probability, and those treated with Memantine alone had a 78.1% probability.

The study calculated mortality rates per 1,000 patient-years for each treatment group. The combined treatment group had the lowest mortality rate at 41.47 deaths per 1,000 patient-years, while the no-treatment, Memantine, and Donepezil groups had rates 36%, 32%, and 42% higher, respectively.

“The research underscores the importance of the combined treatment, suggesting it can extend patients’ lives and reduce medical costs,” said lead author Ehsan Yaghmaei, a professor in the mathematics department at Chapman University. “This comprehensive causal inference study, using a large, high-quality medical database, provides strong evidence for adopting the combined treatment approach to improve patient outcomes and health care efficiency.”

While the findings are promising, the study has some limitations to consider. One significant limitation is the reliance on electronic health records, which may lack detailed information on lifestyle factors, genetic predispositions, and environmental exposures that could influence treatment outcomes. Additionally, the study did not account for Alzheimer’s disease severity, which could affect survival rates.

The study also excluded a significant portion of the original sample (24.3%) who switched treatments during the study period. Future research should explore the effects of treatment changes over time and include more detailed patient information to better understand the factors influencing treatment efficacy.

Nevertheless, the study highlights the potential benefits of combining Donepezil and Memantine for treating Alzheimer’s disease. Given the projected increase in Alzheimer’s cases, with estimates suggesting that 14 million people in the United States will have the disease by 2060, the combined treatment could significantly improve patient outcomes and reduce healthcare costs.

Future research should address the study’s limitations and further investigate the mechanisms behind the observed benefits of the combined treatment. Understanding these mechanisms could lead to even more effective treatment strategies and provide insights into other potential combination therapies for Alzheimer’s disease.

The study, “Combined use of Donepezil and Memantine increases the probability of five-year survival of Alzheimer’s disease patients,” was authored by Ehsan Yaghmaei, Hongxia Lu, Louis Ehwerhemuepha, Jianwei Zheng, Sidy Danioko, Ahmad Rezaie, Seyed Ahmad Sajjadi, and Cyril Rakovski.