Anticholinergic and benzodiazepine medication use and risk of incident dementia:  a UK cohort study

Carlota M Grossi; Kathryn Richardson; Chris Fox; Ian Maidment; Nicholas Steel; Yoon K Loke; Antony Arthur; Phyo Kyaw Myint; Noll Campbell; Malaz Boustani; Louise Robinson; Carol Brayne; Fiona E Matthews; George M Savva

doi:10.1186/s12877-019-1280-2

Anticholinergic and benzodiazepine medication use and risk of incident dementia: a UK cohort study

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

School of Health Sciences, University of East Anglia, Norwich NR4 7TJ, UK.
School of Health Sciences, University of East Anglia, Norwich, NR4 7TJ, UK. [email protected].
Norwich Medical School, University of East Anglia, Earlham Road, Norwich, Norfolk, NR4 7TJ, UK.
Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
Department of Pharmacy Practice, College of Pharmacy, Purdue University, West Lafayette, IN, USA.
Indiana University
Institute of Health and Society/Institute for Ageing, Newcastle University, Newcastle, NE4 5PL, UK.
Cambridge Institute of Public Health, University of Cambridge, Cambridge, CB2 0SR, UK.
Quadram Institute Bioscience, Norwich, Norfolk, UK.

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

52 Citations (SciVal)

52 Downloads (Pure)

Abstract

BACKGROUND: Studies suggest that anticholinergic medication or benzodiazepine use could increase dementia risk. We tested this hypothesis using data from a UK cohort study.

METHODS: We used data from the baseline (Y0), 2-year (Y2) and 10-year (Y10) waves of the Medical Research Council Cognitive Function and Ageing Study. Participants without dementia at Y2 were included (n = 8216). Use of benzodiazepines (including nonbenzodiazepine Z-drugs), anticholinergics with score 3 (ACB3) and anticholinergics with score 1 or 2 (ACB12) according to the Anticholinergic Cognitive Burden scale were coded as ever use (use at Y0 or Y2), recurrent use (Y0 and Y2), new use (Y2, but not Y0) or discontinued use (Y0, but not Y2). The outcome was incident dementia by Y10. Incidence rate ratios (IRR) were estimated using Poisson regression adjusted for potential confounders. Pre-planned subgroup analyses were conducted by age, sex and Y2 Mini-Mental State Examination (MMSE) score.

RESULTS: Dementia incidence was 9.3% (N = 220 cases) between Y2 and Y10. The adjusted IRRs (95%CI) of developing dementia were 1.06 (0.72, 1.60), 1.28 (0.82, 2.00) and 0.89 (0.68, 1.17) for benzodiazepines, ACB3 and ACB12 ever-users compared with non-users. For recurrent users the respective IRRs were 1.30 (0.79, 2.14), 1.68 (1.00, 2.82) and 0.95 (0.71, 1.28). ACB3 ever-use was associated with dementia among those with Y2 MMSE> 25 (IRR = 2.28 [1.32-3.92]), but not if Y2 MMSE≤25 (IRR = 0.94 [0.51-1.73]).

CONCLUSIONS: Neither benzodiazepines nor ACB12 medications were associated with dementia. Recurrent use of ACB3 anticholinergics was associated with dementia, particularly in those with good baseline cognitive function. The long-term prescribing of anticholinergics should be avoided in older people.

Original language	English
Article number	276
Journal	BMC Geriatrics
Volume	19
Issue number	1
DOIs	https://doi.org/10.1186/s12877-019-1280-2
Publication status	Published - 21 Oct 2019

Bibliographical note

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

This work was supported by the UK Alzheimer’s Society [AS-PG-2013-017].

Keywords

Alzheimer disease
Benzodiazepines
Cholinergic antagonists
Cognition
Cohort study
Dementia

Access to Document

10.1186/s12877-019-1280-2Licence: CC BY 3.0

Anticholinergic and benzodiazepine medication
© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Final published version, 708 KBLicence: CC BY 3.0

Cite this

Grossi, C. M., Richardson, K., Fox, C., Maidment, I., Steel, N., Loke, Y. K., Arthur, A., Myint, P. K., Campbell, N., Boustani, M., Robinson, L., Brayne, C., Matthews, F. E., & Savva, G. M. (2019). Anticholinergic and benzodiazepine medication use and risk of incident dementia: a UK cohort study. BMC Geriatrics, 19(1), Article 276. https://doi.org/10.1186/s12877-019-1280-2

@article{ce3a7c6925994d0dad7443229b21eb27,

title = "Anticholinergic and benzodiazepine medication use and risk of incident dementia: a UK cohort study",

abstract = "BACKGROUND: Studies suggest that anticholinergic medication or benzodiazepine use could increase dementia risk. We tested this hypothesis using data from a UK cohort study.METHODS: We used data from the baseline (Y0), 2-year (Y2) and 10-year (Y10) waves of the Medical Research Council Cognitive Function and Ageing Study. Participants without dementia at Y2 were included (n = 8216). Use of benzodiazepines (including nonbenzodiazepine Z-drugs), anticholinergics with score 3 (ACB3) and anticholinergics with score 1 or 2 (ACB12) according to the Anticholinergic Cognitive Burden scale were coded as ever use (use at Y0 or Y2), recurrent use (Y0 and Y2), new use (Y2, but not Y0) or discontinued use (Y0, but not Y2). The outcome was incident dementia by Y10. Incidence rate ratios (IRR) were estimated using Poisson regression adjusted for potential confounders. Pre-planned subgroup analyses were conducted by age, sex and Y2 Mini-Mental State Examination (MMSE) score.RESULTS: Dementia incidence was 9.3\% (N = 220 cases) between Y2 and Y10. The adjusted IRRs (95\%CI) of developing dementia were 1.06 (0.72, 1.60), 1.28 (0.82, 2.00) and 0.89 (0.68, 1.17) for benzodiazepines, ACB3 and ACB12 ever-users compared with non-users. For recurrent users the respective IRRs were 1.30 (0.79, 2.14), 1.68 (1.00, 2.82) and 0.95 (0.71, 1.28). ACB3 ever-use was associated with dementia among those with Y2 MMSE> 25 (IRR = 2.28 [1.32-3.92]), but not if Y2 MMSE≤25 (IRR = 0.94 [0.51-1.73]).CONCLUSIONS: Neither benzodiazepines nor ACB12 medications were associated with dementia. Recurrent use of ACB3 anticholinergics was associated with dementia, particularly in those with good baseline cognitive function. The long-term prescribing of anticholinergics should be avoided in older people.",

keywords = "Alzheimer disease, Benzodiazepines, Cholinergic antagonists, Cognition, Cohort study, Dementia",

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

note = "{\textcopyright} The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. This work was supported by the UK Alzheimer{\textquoteright}s Society [AS-PG-2013-017]. ",

year = "2019",

month = oct,

day = "21",

doi = "10.1186/s12877-019-1280-2",

language = "English",

volume = "19",

journal = "BMC Geriatrics",

publisher = "BioMed Central",

number = "1",

}

TY - JOUR

T1 - Anticholinergic and benzodiazepine medication use and risk of incident dementia

T2 - a UK cohort study

AU - Grossi, Carlota M

AU - Richardson, Kathryn

AU - Fox, Chris

AU - Maidment, Ian

AU - Steel, Nicholas

AU - Loke, Yoon K

AU - Arthur, Antony

AU - Myint, Phyo Kyaw

AU - Campbell, Noll

AU - Boustani, Malaz

AU - Robinson, Louise

AU - Brayne, Carol

AU - Matthews, Fiona E

AU - Savva, George M

N1 - © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. This work was supported by the UK Alzheimer’s Society [AS-PG-2013-017].

PY - 2019/10/21

Y1 - 2019/10/21

N2 - BACKGROUND: Studies suggest that anticholinergic medication or benzodiazepine use could increase dementia risk. We tested this hypothesis using data from a UK cohort study.METHODS: We used data from the baseline (Y0), 2-year (Y2) and 10-year (Y10) waves of the Medical Research Council Cognitive Function and Ageing Study. Participants without dementia at Y2 were included (n = 8216). Use of benzodiazepines (including nonbenzodiazepine Z-drugs), anticholinergics with score 3 (ACB3) and anticholinergics with score 1 or 2 (ACB12) according to the Anticholinergic Cognitive Burden scale were coded as ever use (use at Y0 or Y2), recurrent use (Y0 and Y2), new use (Y2, but not Y0) or discontinued use (Y0, but not Y2). The outcome was incident dementia by Y10. Incidence rate ratios (IRR) were estimated using Poisson regression adjusted for potential confounders. Pre-planned subgroup analyses were conducted by age, sex and Y2 Mini-Mental State Examination (MMSE) score.RESULTS: Dementia incidence was 9.3% (N = 220 cases) between Y2 and Y10. The adjusted IRRs (95%CI) of developing dementia were 1.06 (0.72, 1.60), 1.28 (0.82, 2.00) and 0.89 (0.68, 1.17) for benzodiazepines, ACB3 and ACB12 ever-users compared with non-users. For recurrent users the respective IRRs were 1.30 (0.79, 2.14), 1.68 (1.00, 2.82) and 0.95 (0.71, 1.28). ACB3 ever-use was associated with dementia among those with Y2 MMSE> 25 (IRR = 2.28 [1.32-3.92]), but not if Y2 MMSE≤25 (IRR = 0.94 [0.51-1.73]).CONCLUSIONS: Neither benzodiazepines nor ACB12 medications were associated with dementia. Recurrent use of ACB3 anticholinergics was associated with dementia, particularly in those with good baseline cognitive function. The long-term prescribing of anticholinergics should be avoided in older people.

AB - BACKGROUND: Studies suggest that anticholinergic medication or benzodiazepine use could increase dementia risk. We tested this hypothesis using data from a UK cohort study.METHODS: We used data from the baseline (Y0), 2-year (Y2) and 10-year (Y10) waves of the Medical Research Council Cognitive Function and Ageing Study. Participants without dementia at Y2 were included (n = 8216). Use of benzodiazepines (including nonbenzodiazepine Z-drugs), anticholinergics with score 3 (ACB3) and anticholinergics with score 1 or 2 (ACB12) according to the Anticholinergic Cognitive Burden scale were coded as ever use (use at Y0 or Y2), recurrent use (Y0 and Y2), new use (Y2, but not Y0) or discontinued use (Y0, but not Y2). The outcome was incident dementia by Y10. Incidence rate ratios (IRR) were estimated using Poisson regression adjusted for potential confounders. Pre-planned subgroup analyses were conducted by age, sex and Y2 Mini-Mental State Examination (MMSE) score.RESULTS: Dementia incidence was 9.3% (N = 220 cases) between Y2 and Y10. The adjusted IRRs (95%CI) of developing dementia were 1.06 (0.72, 1.60), 1.28 (0.82, 2.00) and 0.89 (0.68, 1.17) for benzodiazepines, ACB3 and ACB12 ever-users compared with non-users. For recurrent users the respective IRRs were 1.30 (0.79, 2.14), 1.68 (1.00, 2.82) and 0.95 (0.71, 1.28). ACB3 ever-use was associated with dementia among those with Y2 MMSE> 25 (IRR = 2.28 [1.32-3.92]), but not if Y2 MMSE≤25 (IRR = 0.94 [0.51-1.73]).CONCLUSIONS: Neither benzodiazepines nor ACB12 medications were associated with dementia. Recurrent use of ACB3 anticholinergics was associated with dementia, particularly in those with good baseline cognitive function. The long-term prescribing of anticholinergics should be avoided in older people.

KW - Alzheimer disease

KW - Benzodiazepines

KW - Cholinergic antagonists

KW - Cognition

KW - Cohort study

KW - Dementia

UR - https://bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-019-1280-2

UR - https://www.scopus.com/pages/publications/85073708327

U2 - 10.1186/s12877-019-1280-2

DO - 10.1186/s12877-019-1280-2

M3 - Article

C2 - 31638906

VL - 19

JO - BMC Geriatrics

JF - BMC Geriatrics

IS - 1

M1 - 276

ER -