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Richardson, 2018 Anticholinergic drugs and risk of dementia: case-control study


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BMJ 2018; 361 doi: https://doi.org/10.1136/bmj.k1315 (Published 25 April 2018)

Anticholinergic drugs and risk of dementia: case-control study

Kathryn Richardson, research fellow, Chris Fox, professor, Ian Maidment, senior lecturer, Nicholas Steel, professor, Yoon K Loke, professor, Antony Arthur, professor, Phyo K Myint, professor, Carlota M Grossi, senior research associate, Katharina Mattishent, research fellow, Kathleen Bennett, associate professor, Noll L Campbell, assistant professor, Malaz Boustani, professor, Louise Robinson, professor, Carol Brayne, professor, Fiona E Matthews, professor, George M Savva, senior lecturer.


Abstract at: https://www.bmj.com/content/361/bmj.k1315


Objectives To estimate the association between the duration and level of exposure to different classes of anticholinergic drugs and subsequent incident dementia.


Frequency of anticholinergic drugs use During the DEP, 14 453 (35%) cases and 86 403 (30%) controls were prescribed at least one anticholinergic drug with an Anticholinergic Cognitive Burden (ACB) score of 3. A total of 1 793 505 prescriptions for drugs with an ACB score of 3 were written during the DEP. The five most common drugs were amitriptyline (29%), dosulepin (also known as dothiepin; 16%), paroxetine (8%), oxybutynin (7%), and tolterodine (7%). Only 1429 (3.5%) cases and 7909 (2.8%) controls were prescribed drugs with an ACB score of 2, with carbamazepine accounting for 87% of these prescriptions. Most patients (89% of cases and 87% of controls) received at least one prescription for a drug with an ACB score of 1 during the DEP, with cardiovascular drugs accounting for 63% of these prescriptions. The number of prescriptions for each ACB score is further described in supplementary materials, table 1.


Conclusion Many people use anticholinergic drugs at some point in their lives, and many are prescribed to manage chronic conditions leading to potentially long exposures. There are robust associations between levels of anticholinergic antidepressants, antiparkinsons, and urologicals and the risk of a diagnosis of dementia up to 20 years after exposure. Other anticholinergics appear not to be linked to the risk of dementia, and risks remain uncertain for other drugs. Clinicians should continue to be vigilant with respect to the use of anticholinergic drugs, and should consider the risk of long term cognitive effects, as well as short term effects, associated with specific drug classes when performing their risk-benefit analysis.


What is already known on this topic

  • Use of drugs with anticholinergic activity is associated with impaired cognition in the short term

  • It is not known if the reported associations between the use of anticholinergic drugs and future cognitive decline and dementia incidence can be attributed to anticholinergic activity

What this study adds

  • Antidepressant, urological, and antiparkinson drugs with definite anticholinergic activity are linked to future dementia incidence, with associations persisting up to 20 years after exposure

  • Gastrointestinal and cardiovascular anticholinergic drugs are not positively associated with later dementia incidence

  • There is no evidence for a cumulative harm of drugs considered possibly anticholinergic








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