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^* (Corresponding Author), 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

^*Corresponding author for this work

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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
Number of pages	10
Journal	BMC Geriatrics
Volume	19
DOIs	https://doi.org/10.1186/s12877-019-1280-2
Publication status	Published - 21 Oct 2019

Bibliographical note

Availability of data and materials
Data can be shared through application. For further information please refer to the application forms on the website http://www.cfas.ac.uk/cfas-i/data/#cfasi-data-request.

Acknowledgments
We would like to thank the MRC CFAS study group for data collection and management. We are also grateful to all respondents, their families and their primary care teams for their participation in the MRC CFAS. We would like to thank Mr. Barry Plumpton, Mrs. Ann McLauchlan, Mrs. Barbara di Vita, and Mrs. Gloria Swan for providing valuable assistance in interpretation and oversight as Alzheimer’s Society Research Network Volunteers.

Funding
This work was supported by the UK Alzheimer’s Society [AS-PG-2013-017]. The funders had no role in the design of the study or the interpretation of the findings.

Keywords

Alzheimer disease
Cognition
Dementia
Cohort study
Benzodiazepines
Cholinergic antagonists
DRUGS
DISEASE
OLDER
COGNITIVE IMPAIRMENT
PREVALENCE

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© 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.
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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, Article 276. https://doi.org/10.1186/s12877-019-1280-2

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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, Cognition, Dementia, Cohort study, Benzodiazepines, Cholinergic antagonists, DRUGS, DISEASE, OLDER, COGNITIVE IMPAIRMENT, PREVALENCE",

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 = "Availability of data and materials Data can be shared through application. For further information please refer to the application forms on the website http://www.cfas.ac.uk/cfas-i/data/#cfasi-data-request. Acknowledgments We would like to thank the MRC CFAS study group for data collection and management. We are also grateful to all respondents, their families and their primary care teams for their participation in the MRC CFAS. We would like to thank Mr. Barry Plumpton, Mrs. Ann McLauchlan, Mrs. Barbara di Vita, and Mrs. Gloria Swan for providing valuable assistance in interpretation and oversight as Alzheimer{\textquoteright}s Society Research Network Volunteers. Funding This work was supported by the UK Alzheimer{\textquoteright}s Society [AS-PG-2013-017]. The funders had no role in the design of the study or the interpretation of the findings.",

year = "2019",

month = oct,

day = "21",

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

language = "English",

volume = "19",

journal = "BMC Geriatrics",

issn = "1471-2318",

publisher = "BioMed Central",

}

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 - Availability of data and materials Data can be shared through application. For further information please refer to the application forms on the website http://www.cfas.ac.uk/cfas-i/data/#cfasi-data-request. Acknowledgments We would like to thank the MRC CFAS study group for data collection and management. We are also grateful to all respondents, their families and their primary care teams for their participation in the MRC CFAS. We would like to thank Mr. Barry Plumpton, Mrs. Ann McLauchlan, Mrs. Barbara di Vita, and Mrs. Gloria Swan for providing valuable assistance in interpretation and oversight as Alzheimer’s Society Research Network Volunteers. Funding This work was supported by the UK Alzheimer’s Society [AS-PG-2013-017]. The funders had no role in the design of the study or the interpretation of the findings.

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 - Cognition

KW - Dementia

KW - Cohort study

KW - Benzodiazepines

KW - Cholinergic antagonists

KW - DRUGS

KW - DISEASE

KW - OLDER

KW - COGNITIVE IMPAIRMENT

KW - PREVALENCE

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U2 - 10.1186/s12877-019-1280-2

DO - 10.1186/s12877-019-1280-2

M3 - Article

C2 - 31638906

SN - 1471-2318

VL - 19

JO - BMC Geriatrics

JF - BMC Geriatrics

M1 - 276

ER -

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

Abstract

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Keywords

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