Shutterstock.com
Combined treatment with Alzheimer’s disease (AD) drugs donepezil and memantine could extend the lives of approximately 303,000 people living with AD in the United States, a study has found.
The large retrospective cohort study, published in Communications Medicine on 23 May 2024, used data from 12,744 patients, of whom 80% were aged over 76 years, across the United States with a new diagnosis of AD from January 2016 to December 2022, using ‘Oracle Electronic Health Records Real-World Data‘.
The study focused on patients taking two commonly used treatments for AD — donepezil, an acetylcholinesterase inhibitor (28.9%); memantine, a NMDA receptor antagonist (10.7%); and a combination of the two (9.1%) — with a follow-up period of at least five years.
Almost half of the patients (45.5%) received no drug treatment, referred to as the ‘control group’.
Statistical analysis of the patient data found that a combination of donepezil and memantine had the lowest mortality rate of 41.47 per 1,000 patient-years. This was followed by memantine (54.80), no drug treatment (55.96) and donepezil (58.66).
The paper added that — compared with a combination of donepezil and memantine — AD patients who underwent treatment with memantine only, no drug treatment, and treatment with donepezil only, had 32%, 36%, and 42% higher mortality rates, respectively.
Combination therapy significantly increased the probability of five-year survival by 0.05 (6.4%), compared with the control group, owing to a significantly beneficial drug–drug interaction between memantine and donepezil, the researchers said.
They added that the lack of difference in outcome between the monotherapy groups versus the control group may owe to varying stages of AD in each group and alternative factors contributing to patients’ mortality.
Commenting on the study, Colin Davidson, a neuropharmacologist and neurochemist at the University of Central Lancashire, said: “This large US study has found small but significant effects of treating Alzheimer’s patients with a combination of donepezil plus memantine, rather than no drugs, or donepezil or memantine alone.
“An interesting question is how this drug combination is having this effect. Any effect of donepezil or memantine on diabetes, stroke, cardiovascular, or kidney health — all quite prevalent in this population — could account for the decreased mortality,” he added.
“The combination therapy has previously been shown to improve cognitive function, and it may be that this alone is enough to see this small decrease in deaths at five years.
“Another explanation is that it may simply be a placebo effect from patients expecting to feel better because they are taking two pills rather than one.”
AD is the most common form of dementia, accounting for approximately 60–70% of cases globally. The Alzheimer’s Society estimates that there are 982,000 people living with dementia in the UK, which is projected to rise to 1.4 million people in 2040.
According to the Office for National Statistics, dementia and AD were the leading cause of death in 2022, collectively accounting for 65,967 deaths (11.4% of the total) in England and Wales.
Commenting on the study, Hannah Churchill, research communications manager at Alzheimer’s Society, said: “Alzheimer’s Society welcomes this important study, as combining two available drugs would be easy to implement and may give a modest benefit. However, we still don’t know who this combination therapy may work best for as the study didn’t look at lifestyle, genetics, and disease severity.
“As a next step, we’d like to see these combination therapies tested in a clinical trial to fully understand their value.”
