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

doi:10.1136/bmj.k1315

Anticholinergic drugs and risk of dementia: case-control study

Kathryn Richardson^* (Corresponding Author), 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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

273 Citations (Scopus)

19 Downloads (Pure)

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.

Original language	English
Article number	k1315
Number of pages	12
Journal	BMJ
Volume	361
DOIs	https://doi.org/10.1136/bmj.k1315
Publication status	Published - 25 Apr 2018

Bibliographical note

We thank Ms Tarita Murray-Thomas (Medicines and Healthcare products Regulatory Agency) for extracting the CPRD data, Mr Keshav Bajaj (Aston University) for assisting with drugs coding, and Prof Ryan Carnahan for providing the Anticholinergic Drug Scale (ADS). We thank Mr Barry Plumpton, Mrs Ann McLauchlan, Mrs Barbara di Vita, and Mrs Gloria Swan for their assistance and oversight as Alzheimer’s Society Research Network Volunteers.

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.

Access to Document

10.1136/bmj.k1315Licence: CC BY-NC

Anticholinergic drugs and risk of dementia: case-control study
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 non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Final published version, 294 KBLicence: CC BY-NC

Phyo Myint, Clinical Chair in Medicine of Old Age
- School of Medicine, Medical Sciences & Nutrition, Aberdeen Cardiovascular and Diabetes Centre
- School of Medicine, Medical Sciences & Nutrition, Applied Health Sciences - Chair in Old Age Medicine (Clinical)
- Institute of Applied Health Sciences
Person: Clinical Academic

Cite this

@article{68a5ff0169d34918b56773d46a812961,

title = "Anticholinergic drugs and risk of dementia: case-control study",

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.",

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

note = "We thank Ms Tarita Murray-Thomas (Medicines and Healthcare products Regulatory Agency) for extracting the CPRD data, Mr Keshav Bajaj (Aston University) for assisting with drugs coding, and Prof Ryan Carnahan for providing the Anticholinergic Drug Scale (ADS). We thank Mr Barry Plumpton, Mrs Ann McLauchlan, Mrs Barbara di Vita, and Mrs Gloria Swan for their assistance and oversight as Alzheimer{\textquoteright}s Society Research Network Volunteers. Funding: This research was supported by the Alzheimer{\textquoteright}s Society (AS-PG-2013-017). The funders had no role is the design of the study or the interpretation of the findings.",

year = "2018",

month = apr,

day = "25",

doi = "10.1136/bmj.k1315",

language = "English",

volume = "361",

journal = "BMJ",

issn = "0959-8146",

publisher = "BMJ Publishing Group",

}

TY - JOUR

T1 - Anticholinergic drugs and risk of dementia

T2 - case-control study

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 - We thank Ms Tarita Murray-Thomas (Medicines and Healthcare products Regulatory Agency) for extracting the CPRD data, Mr Keshav Bajaj (Aston University) for assisting with drugs coding, and Prof Ryan Carnahan for providing the Anticholinergic Drug Scale (ADS). We thank Mr Barry Plumpton, Mrs Ann McLauchlan, Mrs Barbara di Vita, and Mrs Gloria Swan for their assistance and oversight as Alzheimer’s Society Research Network Volunteers. 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.

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.

U2 - 10.1136/bmj.k1315

DO - 10.1136/bmj.k1315

M3 - Article

C2 - 29695481

SN - 0959-8146

VL - 361

JO - BMJ

JF - BMJ

M1 - k1315

ER -

Anticholinergic drugs and risk of dementia: case-control study

Abstract

Bibliographical note

Access to Document

Fingerprint

Profiles

Phyo Myint, Clinical Chair in Medicine of Old Age

Cite this