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Updated: Sep 11, 2026

A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development
Published on: February 11, 2019
Response to "Comment on cognitive function in the context of pharmacogenetic CYP2D6 variability and anticholinergic
Linda Lorenz1, Judith Berres1, Michael D Denkinger2,3
1Institute of Clinical Pharmacology, University Hospital RWTH Aachen, Aachen, Germany.
Abstract:
We clarify that our analyses were exploratory and hypothesis-generating, with systematic stratification across CYP2D6 metaboliser groups rather than selection based on an interaction p < 0.2 threshold. A post-hoc Benjamini-Hochberg sensitivity analysis provided supportive, but not confirmatory, evidence for the hypothesised stronger association between anticholinergic burden and cognitive function among individuals with reduced CYP2D6 activity. Given the limited subgroup sizes, ceiling effects, and generally high cognitive performance of the cohort, these findings should be considered hypothesis-generating.
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