Related Experiment Video
Updated: Feb 24, 2026
A Machine Learning Approach to Design an Efficient Selective Screening of Mild Cognitive Impairment
Published on: January 11, 2020
Treatment Effects of Cholinesterase Inhibitors in Alzheimer's Disease: a Causal Machine Learning Approach
Etienne Dedebant1, Mathieu Even2, Margaux Törnqvist1
1Theremia, Paris, France.
Introduction:
Treatment response in Alzheimer's disease (AD) varies substantially across patients, yet no validated frameworks exist to estimate heterogeneous treatment effects (HTE) from observational data while controlling for confounding bias.
Methods:
We developed a causal machine learning framework integrating expert-guided causal graphs, complementary HTE estimators, sensitivity analyses, and policy learning. We applied it to cholinesterase inhibitors (ChEIs) in MCI due to AD to patients from the NACC and ADNI cohorts.
Results:
Analysing 4,049 patients with 12-month and 2,223 with 36-month follow-up, all estimators indicated null or negative long-term ChEI effects on cognitive and functional outcomes, notably on functional measures. ChEIs showed slightly more deleterious effects among men than women.
Discussion:
This framework provides a methodology for estimating HTE from observational data. It revealed no beneficial responder subgroups, highlighting the challenge of detecting treatment heterogeneity in moderately sized cohorts. This approach can inform treatment selection for other AD therapies including memantine, anti-amyloid agents, and emerging treatments.
More Related Videos
09:47Author Spotlight: Advancing Alzheimer's Research – Exploring Early Detection and Multi-Omics Approaches
Published on: December 15, 2023
08:01Intracerebroventricular Injection of Amyloid-β Peptides in Normal Mice to Acutely Induce Alzheimer-like Cognitive Deficits
Published on: March 16, 2016
Related Concept Videos
01:22Alzheimer's Disease: Treatment
01:30Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
01:26Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
01:30Indirect-Acting Cholinergic Agonists: Pharmacological Actions
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
01:26Anticholinesterase Agents: Poisoning and Treatment
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...