Anticholinergic burden and incident dementia: a Swedish nationwide case-control study

Cumulative exposure to multiple drugs with anticholinergic properties, known as anticholinergic burden, has been linked to dementia risk. We aimed to thoroughly assess this relationship by examining not only anticholinergic potency, cumulative dose, and drug class, but also dementia subtype and severity.

This Swedish nationwide case-control study included 199,526 individuals aged ≥ 40 years with incident dementia between July 2008 and December 2017, with 1:1 matched controls based on age, sex, and region of residence. Each case-control group was allocated an identical drug exposure period. Using the Anticholinergic Cognitive Burden (ACB) scale, we separately calculated the total defined daily doses (DDDs) of drugs with weak (ACB score of 1) and strong anticholinergic properties (ACB score of 2-3) prescribed ≥ 1 year before dementia onset. Conditional logistic regression was used to estimate the adjusted odds ratios (AORs) for the association between anticholinergic burden and all-cause dementia, with additional stratified analyses by drug class, dementia subtypes, and severity.

A nonlinear dose-response relationship with all-cause dementia was found for the cumulative use of strong anticholinergics (e.g., 1-89 DDDs: AOR, 1.10 [95% CI, 1.08-1.12]; ≥1095 DDDs: AOR, 1.66 [95% CI, 1.55-1.79]), notably within the class of urinary antispasmodics, antihistamines, and psychotropic drugs. In contrast, a subtle association lacking a dose-response pattern was observed for weak anticholinergics (e.g., 1-89 DDDs: AOR, 1.11 [95% CI, 1.08-1.13]; ≥1095 DDDs: AOR, 1.01 [95% CI, 0.98-1.03]). The associations with strong anticholinergics were more pronounced in men, younger people, those diagnosed with vascular dementia or Lewy body dementia (versus Alzheimer's disease), and those with milder-stage dementia.

Use of strong anticholinergics, but not weak ones, was associated with a higher risk of dementia, with the strength of association depending on cumulative dose, drug class, and dementia subtype. Caution should be exercised when prescribing drugs with strong anticholinergic properties to middle-aged and older individuals.