The University of Southampton
University of Southampton Institutional Repository
Warning ePrints Soton is experiencing an issue with some file downloads not being available. We are working hard to fix this. Please bear with us.

Anticholinergic drug exposure and the risk of dementia - A nested case-control study

Anticholinergic drug exposure and the risk of dementia - A nested case-control study
Anticholinergic drug exposure and the risk of dementia - A nested case-control study
Importance:  Anticholinergic medicines have short-term cognitive adverse effects, but it is uncertain whether long-term use of these drugs is associated with an increased risk of dementia.
Objective: To assess associations between anticholinergic drug treatments and risk of dementia in persons 55 years or older.Design, Setting, and Participants: This nested case-control study took place in general practices in England that contributed to the QResearch primary care database. The study evaluated whether exposure to anticholinergic drugs was associated with dementia risk in 58 769 patients with a diagnosis of dementia and 225 574 controls 55 years or older matched by age, sex, general practice, and calendar time. Information on prescriptions for 56 drugs with strong anticholinergic properties was used to calculate measures of cumulative anticholinergic drug exposure. Data were analyzed from May 2016 to June 2018.Exposures: The primary exposure was the total standardized daily doses (TSDDs) of anticholinergic drugs prescribed in the 1 to 11 years prior to the date of diagnosis of dementia or equivalent date in matched controls (index date).
Main Outcomes and Measures: Odds ratios (ORs) for dementia associated with cumulative exposure to anticholinergic drugs, adjusted for confounding variables.
Results: Of the entire study population (284 343 case patients and matched controls), 179 365 (63.1%) were women, and the mean (SD) age of the entire population was 82.2 (6.8) years. The adjusted OR for dementia increased from 1.06 (95% CI, 1.03-1.09) in the lowest overall anticholinergic exposure category (total exposure of 1-90 TSDDs) to 1.49 (95% CI, 1.44-1.54) in the highest category (>1095 TSDDs), compared with no anticholinergic drug prescriptions in the 1 to 11 years before the index date. There were significant increases in dementia risk for the anticholinergic antidepressants (adjusted OR [AOR], 1.29; 95% CI, 1.24-1.34), antiparkinson drugs (AOR, 1.52; 95% CI, 1.16-2.00), antipsychotics (AOR, 1.70; 95% CI, 1.53-1.90), bladder antimuscarinic drugs (AOR, 1.65; 95% CI, 1.56-1.75), and antiepileptic drugs (AOR, 1.39; 95% CI, 1.22-1.57) all for more than 1095 TSDDs. Results were similar when exposures were restricted to exposure windows of 3 to 13 years (AOR, 1.46; 95% CI, 1.41-1.52) and 5 to 20 years (AOR, 1.44; 95% CI, 1.32-1.57) before the index date for more than 1095 TSDDs. Associations were stronger in cases diagnosed before the age of 80 years. The population-attributable fraction associated with total anticholinergic drug exposure during the 1 to 11 years before diagnosis was 10.3%.
Conclusions and Relevance: Exposure to several types of strong anticholinergic drugs is associated with an increased risk of dementia. These findings highlight the importance of reducing exposure to anticholinergic drugs in middle-aged and older people.
2168-6106
1084-1093
Coupland, Carol
6efd69d5-8f84-45ac-9777-d4b07feeb2e2
Hill, Trevor
7c347407-2cde-4145-9a38-6e4258af6982
Dening, Tom
9a76d578-8130-4559-928a-752bbc2db082
Morriss, Richard
fb48ce6f-f557-4e5d-a309-5eb7f6ee6c2e
Moore, Michael
1be81dad-7120-45f0-bbed-f3b0cc0cfe99
Hippisley-Cox, Julia
7be524e3-9066-4179-b58f-cb2e16cd02ec
Coupland, Carol
6efd69d5-8f84-45ac-9777-d4b07feeb2e2
Hill, Trevor
7c347407-2cde-4145-9a38-6e4258af6982
Dening, Tom
9a76d578-8130-4559-928a-752bbc2db082
Morriss, Richard
fb48ce6f-f557-4e5d-a309-5eb7f6ee6c2e
Moore, Michael
1be81dad-7120-45f0-bbed-f3b0cc0cfe99
Hippisley-Cox, Julia
7be524e3-9066-4179-b58f-cb2e16cd02ec

Coupland, Carol, Hill, Trevor, Dening, Tom, Morriss, Richard, Moore, Michael and Hippisley-Cox, Julia (2019) Anticholinergic drug exposure and the risk of dementia - A nested case-control study. JAMA Internal Medicine, 179 (8), 1084-1093. (doi:10.1001/jamainternmed.2019.0677).

Record type: Article

Abstract

Importance:  Anticholinergic medicines have short-term cognitive adverse effects, but it is uncertain whether long-term use of these drugs is associated with an increased risk of dementia.
Objective: To assess associations between anticholinergic drug treatments and risk of dementia in persons 55 years or older.Design, Setting, and Participants: This nested case-control study took place in general practices in England that contributed to the QResearch primary care database. The study evaluated whether exposure to anticholinergic drugs was associated with dementia risk in 58 769 patients with a diagnosis of dementia and 225 574 controls 55 years or older matched by age, sex, general practice, and calendar time. Information on prescriptions for 56 drugs with strong anticholinergic properties was used to calculate measures of cumulative anticholinergic drug exposure. Data were analyzed from May 2016 to June 2018.Exposures: The primary exposure was the total standardized daily doses (TSDDs) of anticholinergic drugs prescribed in the 1 to 11 years prior to the date of diagnosis of dementia or equivalent date in matched controls (index date).
Main Outcomes and Measures: Odds ratios (ORs) for dementia associated with cumulative exposure to anticholinergic drugs, adjusted for confounding variables.
Results: Of the entire study population (284 343 case patients and matched controls), 179 365 (63.1%) were women, and the mean (SD) age of the entire population was 82.2 (6.8) years. The adjusted OR for dementia increased from 1.06 (95% CI, 1.03-1.09) in the lowest overall anticholinergic exposure category (total exposure of 1-90 TSDDs) to 1.49 (95% CI, 1.44-1.54) in the highest category (>1095 TSDDs), compared with no anticholinergic drug prescriptions in the 1 to 11 years before the index date. There were significant increases in dementia risk for the anticholinergic antidepressants (adjusted OR [AOR], 1.29; 95% CI, 1.24-1.34), antiparkinson drugs (AOR, 1.52; 95% CI, 1.16-2.00), antipsychotics (AOR, 1.70; 95% CI, 1.53-1.90), bladder antimuscarinic drugs (AOR, 1.65; 95% CI, 1.56-1.75), and antiepileptic drugs (AOR, 1.39; 95% CI, 1.22-1.57) all for more than 1095 TSDDs. Results were similar when exposures were restricted to exposure windows of 3 to 13 years (AOR, 1.46; 95% CI, 1.41-1.52) and 5 to 20 years (AOR, 1.44; 95% CI, 1.32-1.57) before the index date for more than 1095 TSDDs. Associations were stronger in cases diagnosed before the age of 80 years. The population-attributable fraction associated with total anticholinergic drug exposure during the 1 to 11 years before diagnosis was 10.3%.
Conclusions and Relevance: Exposure to several types of strong anticholinergic drugs is associated with an increased risk of dementia. These findings highlight the importance of reducing exposure to anticholinergic drugs in middle-aged and older people.

Text
Anticholinergic drugs and the risk of dementia_paper_revised short version3 - Author's Original
Restricted to Repository staff only
Request a copy
Text
Anticholinergic drugs and the risk of dementia_supplement - Author's Original
Restricted to Repository staff only
Request a copy
Text
jamainternal_coupland_2019_oi_190025 - Version of Record
Available under License Creative Commons Attribution.
Download (239kB)

More information

Accepted/In Press date: 19 February 2019
e-pub ahead of print date: 24 June 2019
Published date: 1 August 2019

Identifiers

Local EPrints ID: 432251
URI: http://eprints.soton.ac.uk/id/eprint/432251
ISSN: 2168-6106
PURE UUID: 575c9008-1faf-4cc2-987b-147047be84a1
ORCID for Michael Moore: ORCID iD orcid.org/0000-0002-5127-4509

Catalogue record

Date deposited: 05 Jul 2019 16:30
Last modified: 26 Nov 2021 02:49

Export record

Altmetrics

Contributors

Author: Carol Coupland
Author: Trevor Hill
Author: Tom Dening
Author: Richard Morriss
Author: Michael Moore ORCID iD
Author: Julia Hippisley-Cox

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×