Anticholinergic drugs and risk of dementia: case-control studyBMJ 2018; 361 doi: https://doi.org/10.1136/bmj.k1315 (Published 25 April 2018) Cite this as: BMJ 2018;361:k1315
- Kathryn Richardson, research fellow1,
- Chris Fox, professor2,
- Ian Maidment, senior lecturer3,
- Nicholas Steel, professor2,
- Yoon K Loke, professor2,
- Antony Arthur, professor1,
- Phyo K Myint, professor4,
- Carlota M Grossi, senior research associate1,
- Katharina Mattishent, research fellow2,
- Kathleen Bennett, associate professor5,
- Noll L Campbell, assistant professor6,
- Malaz Boustani, professor7,
- Louise Robinson, professor8,
- Carol Brayne, professor9,
- Fiona E Matthews, professor10,
- George M Savva, senior lecturer1
- 1School of Health Sciences, University of East Anglia, Norwich NR4 7TJ, UK
- 2Norwich Medical School, University of East Anglia, Norwich, UK
- 3School of Life and Health Sciences, Aston University, Birmingham, UK
- 4School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK
- 5Division of Population Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland
- 6Department of Pharmacy Practice, College of Pharmacy, Purdue University, West Lafayette, IN, USA
- 7School of Medicine, Indiana University, Indianapolis, IN, USA
- 8Institute for Ageing, Newcastle University, Newcastle upon Tyne, UK
- 9Cambridge Institute of Public Health, University of Cambridge, Cambridge, UK
- 10Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK
- Correspondence to: K Richardson
- Accepted 7 March 2018
Objectives To estimate the association between the duration and level of exposure to different classes of anticholinergic drugs and subsequent incident dementia.
Design Case-control study.
Setting General practices in the UK contributing to the Clinical Practice Research Datalink.
Participants 40 770 patients aged 65-99 with a diagnosis of dementia between April 2006 and July 2015, and 283 933 controls without dementia.
Interventions Daily defined doses of anticholinergic drugs coded using the Anticholinergic Cognitive Burden (ACB) scale, in total and grouped by subclass, prescribed 4-20 years before a diagnosis of dementia.
Main outcome measures Odds ratios for incident dementia, adjusted for a range of demographic and health related covariates.
Results 14 453 (35%) cases and 86 403 (30%) controls were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. The adjusted odds ratio for any anticholinergic drug with an ACB score of 3 was 1.11 (95% confidence interval 1.08 to 1.14). Dementia was associated with an increasing average ACB score. When considered by drug class, gastrointestinal drugs with an ACB score of 3 were not distinctively linked to dementia. The risk of dementia increased with greater exposure for antidepressant, urological, and antiparkinson drugs with an ACB score of 3. This result was also observed for exposure 15-20 years before a diagnosis.
Conclusions A robust association between some classes of anticholinergic drugs and future dementia incidence was observed. This could be caused by a class specific effect, or by drugs being used for very early symptoms of dementia. Future research should examine anticholinergic drug classes as opposed to anticholinergic effects intrinsically or summing scales for anticholinergic exposure.
Trial registration Registered to the European Union electronic Register of Post-Authorisation Studies EUPAS8705.
Contributors: KR, CF, GMS, PKM, and IM conceived and developed the initial study. KR and GMS drafted the statistical analysis plan. KR, NS, IM, CF, and NLC developed the code lists. KR conducted the statistical analysis. All authors contributed to the study protocol development and revision, the interpretation of findings, and the revision of the manuscript. KR is the guarantor.
Funding: This research was supported by the Alzheimer’s Society (AS-PG-2013-017). The funders had no role is the design of the study or the interpretation of the findings.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work beyond the Alzheimer's Society grant. IM reports personal fees for guest lectures from Astellas Pharmaceuticals. YL reports personal fees from Thame Pharmaceuticals. NC and CF report grants and personal fees from Astellas Pharmaceuticals.
Ethical approval: The study was approved by the Independent Scientific Advisory Committee for Clinical Practice Research Datalink (CPRD) research (protocol No 15_056R). No further ethical approval was required for the analysis of the data. CPRD has obtained ethical approval from a multicentre research ethics committee for all purely observational research using CPRD data.
Data sharing: Data from the Clinical Practice Research Datalink (CPRD) is available directly from CPRD. Full code lists are available from the corresponding author at email@example.com.
Transparency: The lead author (KR) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned and registered have been explained.
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