Anticholinergic Drug Use and Dementia: What's the Link?

Antidepressants and urologicals with an ABC score of 3 were consistently associated with incident dementia
Antidepressants and urologicals with an ABC score of 3 were consistently associated with incident dementia

The use of certain anticholinergic drugs may increase the risk of future dementia, according to a new case-control study published in the BMJ.

Previous literature has linked anticholinergic use to dementia, however these studies have been limited by their inability to determine if the increased risk is specific to the drug or the underlying conditions for which they were prescribed. 

To examine these associations, researchers used multiple conditional logistic regression to evaluate patients with a new diagnosis of dementia and compared their anticholinergic drug use 4–20 years before diagnosis; they were then matched to a control group without dementia. The data was obtained from the Clinical Practice Research Datalink (CPRD), which includes records from 674 practices across the UK.

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A total of 14,453 (35%) cases and 86,403 (30%) controls were prescribed at least 1 anticholingeric drug with an Anticholinergic Cognitive Burden (ACB) score of 3; 1429 (3.5%) cases and 7909 (2.8%) controls were prescribed drugs with an ACB score of 2; most patients (89% of cases and 87% of controls) received a drug with an ACB score of 1 during the drug exposure period (DEP).

Results demonstrated a significant link between any ACB drug score and dementia (odds ratios 1.10, 1.10 and 1.11 for scores 1, 2, and 3, respectively), with a dose-response effect seen for doses of drugs with scores 2 or 3. There was a positive association for antidepressants with an ACB 1 score and dementia risk; no other drugs with an ACB score of 1 had this association.

Antidepressants (primarily amitriptyline, dosulepin [also known as dothiepin], and paroxetine), and urologicals (primarily oxybutynin and tolterodine) with an ACB score of 3 were consistently associated with incident dementia. Antidepressants with an ACB score of 3 were associated with an odds ratio of 1.3 (95% CI: 1.10 to 1.16) at the start of DEP and an odds ratio of 1.11 (95% CI: 1.08 to 1.14) at the end of DEP. Conversely, the use of gastrointestinal drugs (ACB score 1 or 3) and cardiovascular drugs (ACB score 1) was linked to a minor reduction in dementia risk.

Although the associations discovered in the study are moderate (odds ratios range:1.1–1.3), the authors write that "given the high incidence of dementia they reflect an appreciable risk to patients." They conclude that clinicians should be vigilant with respect to anticholinergic drugs and should consider long-term cognitive effects.

For more information visit BMJ.com.