Anticholinergic drugs and risk of dementia: case-control study

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

Research output: Contribution to journalArticle

Abstract

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.

LanguageEnglish
Article numberk1315
JournalBMJ (Clinical research ed.)
Volume361
DOIs
Publication statusPublished - 25 Apr 2018

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Cholinergic Antagonists
Dementia
Case-Control Studies
Pharmaceutical Preparations
Odds Ratio
Antiparkinson Agents
Gastrointestinal Agents
European Union
General Practice
Antidepressive Agents

Bibliographical note

This is an Open Access article distributed in accordance with the
Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license,
which permits others to distribute, remix, adapt, build upon this work
non-commercially, and license their derivative works on different
terms, provided the original work is properly cited and the use is noncommercial.
See: http://creativecommons.org/licenses/by-nc/4.0/.

Cite this

Richardson, K., Fox, C., Maidment, I., Steel, N., Loke, Y. K., Arthur, A., ... Savva, G. M. (2018). Anticholinergic drugs and risk of dementia: case-control study. BMJ (Clinical research ed.), 361, [k1315]. https://doi.org/10.1136/bmj.k1315
Richardson, Kathryn ; Fox, Chris ; Maidment, Ian ; Steel, Nicholas ; Loke, Yoon K ; Arthur, Antony ; Myint, Phyo K ; Grossi, Carlota M ; Mattishent, Katharina ; Bennett, Kathleen ; Campbell, Noll L ; Boustani, Malaz ; Robinson, Louise ; Brayne, Carol ; Matthews, Fiona E ; Savva, George M. / Anticholinergic drugs and risk of dementia : case-control study. In: BMJ (Clinical research ed.). 2018 ; Vol. 361.
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Richardson, K, Fox, C, Maidment, I, Steel, N, Loke, YK, Arthur, A, Myint, PK, Grossi, CM, Mattishent, K, Bennett, K, Campbell, NL, Boustani, M, Robinson, L, Brayne, C, Matthews, FE & Savva, GM 2018, 'Anticholinergic drugs and risk of dementia: case-control study' BMJ (Clinical research ed.), vol. 361, k1315. https://doi.org/10.1136/bmj.k1315

Anticholinergic drugs and risk of dementia : case-control study. / Richardson, Kathryn; Fox, Chris; Maidment, Ian; Steel, Nicholas; Loke, Yoon K; Arthur, Antony; Myint, Phyo K; Grossi, Carlota M; Mattishent, Katharina; Bennett, Kathleen; Campbell, Noll L; Boustani, Malaz; Robinson, Louise; Brayne, Carol; Matthews, Fiona E; Savva, George M.

In: BMJ (Clinical research ed.), Vol. 361, k1315, 25.04.2018.

Research output: Contribution to journalArticle

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T1 - Anticholinergic drugs and risk of dementia

T2 - BMJ

AU - Richardson, Kathryn

AU - Fox, Chris

AU - Maidment, Ian

AU - Steel, Nicholas

AU - Loke, Yoon K

AU - Arthur, Antony

AU - Myint, Phyo K

AU - Grossi, Carlota M

AU - Mattishent, Katharina

AU - Bennett, Kathleen

AU - Campbell, Noll L

AU - Boustani, Malaz

AU - Robinson, Louise

AU - Brayne, Carol

AU - Matthews, Fiona E

AU - Savva, George M

N1 - This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

PY - 2018/4/25

Y1 - 2018/4/25

N2 - 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.

AB - 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.

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DO - 10.1136/bmj.k1315

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JF - BMJ

SN - 0959-8138

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