open access, at least for now
Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study
Carol A. C. Coupland, PhD; Trevor Hill, MSc; Tom Dening, MD; et al
JAMA Intern Med. Published online June 24, 2019. doi:10.1001/jamainternmed.2019.0677
A more detailed review of dementia risks associated with various anticholinergic drugs. Results are consistent with previous studies which have been noted on the forum. Note that their headline worst case relative risk (~50%) isn't at all the same as a typical absolute risk.
This large, nested case-control study found an increased risk of dementia associated with anticholinergic medication use. Associations were strongest for the anticholinergic antidepressants, bladder antimuscarinics, antipsychotics, and antiepileptic drugs. Associations were also stronger in cases diagnosed before the age of 80 years and in cases diagnosed with vascular dementia rather than with Alzheimer disease. There were no significantly increased risks for antihistamines, gastrointestinal antispasmodics, antimuscarinic bronchodilators, antiarrhythmics, or skeletal muscle relaxants, although the numbers of patients prescribed skeletal muscle relaxants and antiarrhythmic drugs were small, giving imprecise estimates.
There was nearly a 50% increased odds of dementia associated with total anticholinergic exposure of more than 1095 TSDDs within a 10-year period, which is equivalent to 3 years’ daily use of a single strong anticholinergic medication at the minimum effective dose recommended for older people. This observational study has shown associations, but is not able to evaluate causality. ...
The finding of more pronounced associations for vascular dementia than for other types is novel. It raises questions about the mechanisms by which anticholinergic drugs may increase the risk of subsequent dementia. These may include vascular and inflammatory changes,33,34 as well as the more obvious mechanism of chronic cholinergic depletion. Perhaps the mechanism underlying the potential effects of anticholinergic drugs is not solely through blocking acetylcholine and causing an excess of Alzheimer disease, so future research should give consideration to possible mechanisms.
See the "FIGURES/TABLES" tab (upper right) on the web page for some interesting tables. (Or click the Download PDF button in the upper left.)