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Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study

Carol A. C. Coupland, PhD; Trevor Hill, MSc; TomDening, MD; Richard Morriss, MD; Michael Moore, MSc; Julia Hippisley-Cox, MD

JAMA Intern Med. Published online June 24, 2019. doi:10.1001/jamainternmed.2019.0677

Coupland et al carried out a nested case-control study based on the QResearch primary care database from England, including 58 769 patients with a diagnosis of dementia and 225 574 controls 55 years or older matched by age, sex, general practice, and calendar time. Information on prescriptions for 56 drugs with strong anticholinergic properties was used to calculate measures of cumulative anticholinergic drug exposure.

Primary exposure was defined as the total standardized daily doses (TSDDs) of anticholinergic drugs prescribed in the 1 to 11 years prior to the date of diagnosis of dementia or equivalent date in matched controls (index date).

Having into account the entire study population (284 343 case patients and matched controls), 179 365 (63.1%) were women, and the mean (SD) age of the entire population was 82.2 (6.8) years. 

The adjusted OR for dementia increased from 1.06 (95%CI, 1.03-1.09) in the lowest overall anticholinergic exposure category (total exposure of 1-90 TSDDs) to 1.49 (95%CI, 1.44-1.54) in the highest category (>1095 TSDDs), compared with no anticholinergic drug prescriptions in the 1 to 11 years before the index date. 

There were significant increases in dementia risk for the anticholinergic antidepressants (adjusted OR [AOR], 1.29; 95%CI, 1.24-1.34), antiparkinson drugs (AOR, 1.52; 95%CI, 1.16-2.00), antipsychotics (AOR, 1.70; 95% CI, 1.53-1.90), bladder antimuscarinic drugs (AOR, 1.65; 95%CI, 1.56-1.75), and antiepileptic drugs (AOR, 1.39; 95%CI, 1.22-1.57) all for more than 1095 TSDDs. Results were similar when exposures were restricted to exposure windows of 3 to 13 years (AOR, 1.46; 95%CI, 1.41-1.52) and 5 to 20 years (AOR, 1.44; 95%CI, 1.32-1.57) before the index date for more than 1095 TSDDs. Associations were stronger in cases diagnosed before the age of 80 years. 



Comment by Marcio Averbeck:

There is increasing evidence for a possible causal association between the chronic use of anticholinergics and the risk of developing dementia. The inherent limitation for establishing such causal nexus is precisely the fact that the prevalence of overactive bladder (OAB) symptoms and the prescription of antimuscarinics tends to increase in older individuals, exactly in the same age groups in which the incidence of dementia is higher. Despite attempts to control for confounding variables, the results of case-control studies should be viewed with caution. Even so, this is not the first study to suggest an association between the chronic use of anticholinergics and the development of dementia. Physicians should be aware of new evidences and attempt to reduce exposure to anticholinergic drugs in middle-aged and older people.

But are all antimuscarinics alike?
Which antimuscarinic would you prefer for eldery persons? 

Please send your opinion to info@neuro-uro.org


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