Beneficial effects of anticholinesterases: Reducing the anticholinergic load, the missing link of the story?

Anticholinergic effects are often identified as adverse drug effects. They can manifest at the central level with cognitive disorders and peripherally with various symptoms such as dry mucous membranes, constipation, urinary retention, or even tachycardia. Several studies have also shown that a high anticholinergic burden may be associated with an increased risk of dementia, hospitalization and even mortality. On the other hand, anticholinesterase drugs, through their protective action on acetylcholine, improve cognitive functions but may cause adverse effects such as diarrhea, urinary incontinence, and bradycardia. Large retrospective cohort studies have also shown that anticholinesterase drugs are associated with a reduced risk of mortality. We thus hypothesize, based on these opposing effects, that the symptomatic improvements, both central and peripheral, observed with anticholinesterase drugs could be linked, at least in part, to the reduction of the anticholinergic burden. Further studies are needed to confirm this hypothesis. These studies should investigate the potential positive correlation between the beneficial effects observed with anticholinesterase drugs and the anticholinergic burden.