Anticholinergic drugs and incident dementia, mild cognitive impairment and cognitive decline: a meta-analysis

Nina T Pieper; Carlota M Grossi; Wei-Yee Chan; Yoon K Loke; George M Savva; Clara Haroulis; Nicholas Steel; Chris Fox; Ian D Maidment; Antony J Arthur; Phyo K Myint; Toby O Smith; Louise Robinson; Fiona E Matthews; Carol Brayne; Kathryn Richardson

doi:10.1093/ageing/afaa090

Anticholinergic drugs and incident dementia, mild cognitive impairment and cognitive decline: a meta-analysis

Nina T Pieper, Carlota M Grossi, Wei-Yee Chan, Yoon K Loke, George M Savva, Clara Haroulis, Nicholas Steel, Chris Fox, Ian D Maidment, Antony J Arthur, Phyo K Myint, Toby O Smith, Louise Robinson, Fiona E Matthews, Carol Brayne, Kathryn Richardson

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

Abstract

BACKGROUND: the long-term effect of the use of drugs with anticholinergic activity on cognitive function remains unclear.

METHODS: we conducted a systematic review and meta-analysis of the relationship between anticholinergic drugs and risk of dementia, mild cognitive impairment (MCI) and cognitive decline in the older population. We identified studies published between January 2002 and April 2018 with ≥12 weeks follow-up between strongly anticholinergic drug exposure and the study outcome measurement. We pooled adjusted odds ratios (OR) for studies reporting any, and at least short-term (90+ days) or long-term (365+ days) anticholinergic use for dementia and MCI outcomes, and standardised mean differences (SMD) in global cognition test scores for cognitive decline outcomes. Statistical heterogeneity was measured using the I2 statistic and risk of bias using ROBINS-I.

RESULTS: twenty-six studies (including 621,548 participants) met our inclusion criteria. 'Any' anticholinergic use was associated with incident dementia (OR 1.20, 95% confidence interval [CI] 1.09-1.32, I2 = 86%). Short-term and long-term use were also associated with incident dementia (OR 1.23, 95% CI 1.17-1.29, I2 = 2%; and OR 1.50, 95% CI 1.22-1.85, I2 = 90%). 'Any' anticholinergic use was associated with cognitive decline (SMD 0.15; 95% CI 0.09-0.21, I2 = 3%) but showed no statistically significant difference for MCI (OR 1.24, 95% CI 0.97-1.59, I2 = 0%).

CONCLUSIONS: anticholinergic drug use is associated with increased dementia incidence and cognitive decline in observational studies. However, a causal link cannot yet be inferred, as studies were observational with considerable risk of bias. Stronger evidence from high-quality studies is needed to guide the management of long-term use.

Original language	English
Pages (from-to)	939-947
Number of pages	9
Journal	Age and Ageing
Volume	49
Issue number	6
Early online date	29 Jun 2020
DOIs	https://doi.org/10.1093/ageing/afaa090
Publication status	Published - 23 Oct 2020

Bibliographical note

© The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society.
This is an Open Access article distributed under the terms of the Creative Commons Attribution
Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits
non-commercial re-use, distribution, and reproduction in any medium, provided the original work is
properly cited. For commercial re-use, please contact [email protected]
Funding: This work was supported by the Alzheimer’s Society UK [AS-PG-2013-017].

Keywords

anticholinergics
cognition
dementia
meta-analysis
older people
systematic review

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10.1093/ageing/afaa090Licence: CC BY-NC 3.0

Anticholinergic drugs and incident dementia
© The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected]
Final published version, 554 KBLicence: CC BY-NC 3.0

Cite this

Pieper, N. T., Grossi, C. M., Chan, W.-Y., Loke, Y. K., Savva, G. M., Haroulis, C., Steel, N., Fox, C., Maidment, I. D., Arthur, A. J., Myint, P. K., Smith, T. O., Robinson, L., Matthews, F. E., Brayne, C., & Richardson, K. (2020). Anticholinergic drugs and incident dementia, mild cognitive impairment and cognitive decline: a meta-analysis. Age and Ageing, 49(6), 939-947. https://doi.org/10.1093/ageing/afaa090

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title = "Anticholinergic drugs and incident dementia, mild cognitive impairment and cognitive decline: a meta-analysis",

abstract = "BACKGROUND: the long-term effect of the use of drugs with anticholinergic activity on cognitive function remains unclear.METHODS: we conducted a systematic review and meta-analysis of the relationship between anticholinergic drugs and risk of dementia, mild cognitive impairment (MCI) and cognitive decline in the older population. We identified studies published between January 2002 and April 2018 with ≥12 weeks follow-up between strongly anticholinergic drug exposure and the study outcome measurement. We pooled adjusted odds ratios (OR) for studies reporting any, and at least short-term (90+ days) or long-term (365+ days) anticholinergic use for dementia and MCI outcomes, and standardised mean differences (SMD) in global cognition test scores for cognitive decline outcomes. Statistical heterogeneity was measured using the I2 statistic and risk of bias using ROBINS-I.RESULTS: twenty-six studies (including 621,548 participants) met our inclusion criteria. 'Any' anticholinergic use was associated with incident dementia (OR 1.20, 95% confidence interval [CI] 1.09-1.32, I2 = 86%). Short-term and long-term use were also associated with incident dementia (OR 1.23, 95% CI 1.17-1.29, I2 = 2%; and OR 1.50, 95% CI 1.22-1.85, I2 = 90%). 'Any' anticholinergic use was associated with cognitive decline (SMD 0.15; 95% CI 0.09-0.21, I2 = 3%) but showed no statistically significant difference for MCI (OR 1.24, 95% CI 0.97-1.59, I2 = 0%).CONCLUSIONS: anticholinergic drug use is associated with increased dementia incidence and cognitive decline in observational studies. However, a causal link cannot yet be inferred, as studies were observational with considerable risk of bias. Stronger evidence from high-quality studies is needed to guide the management of long-term use.",

keywords = "anticholinergics, cognition, dementia, meta-analysis, older people, systematic review",

author = "Pieper, {Nina T} and Grossi, {Carlota M} and Wei-Yee Chan and Loke, {Yoon K} and Savva, {George M} and Clara Haroulis and Nicholas Steel and Chris Fox and Maidment, {Ian D} and Arthur, {Antony J} and Myint, {Phyo K} and Smith, {Toby O} and Louise Robinson and Matthews, {Fiona E} and Carol Brayne and Kathryn Richardson",

note = "{\textcopyright} The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] Funding: This work was supported by the Alzheimer{\textquoteright}s Society UK [AS-PG-2013-017].",

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doi = "10.1093/ageing/afaa090",

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Pieper, NT, Grossi, CM, Chan, W-Y, Loke, YK, Savva, GM, Haroulis, C, Steel, N, Fox, C, Maidment, ID, Arthur, AJ, Myint, PK, Smith, TO, Robinson, L, Matthews, FE, Brayne, C & Richardson, K 2020, 'Anticholinergic drugs and incident dementia, mild cognitive impairment and cognitive decline: a meta-analysis', Age and Ageing, vol. 49, no. 6, pp. 939-947. https://doi.org/10.1093/ageing/afaa090

TY - JOUR

T1 - Anticholinergic drugs and incident dementia, mild cognitive impairment and cognitive decline

T2 - a meta-analysis

AU - Pieper, Nina T

AU - Grossi, Carlota M

AU - Chan, Wei-Yee

AU - Loke, Yoon K

AU - Savva, George M

AU - Haroulis, Clara

AU - Steel, Nicholas

AU - Fox, Chris

AU - Maidment, Ian D

AU - Arthur, Antony J

AU - Myint, Phyo K

AU - Smith, Toby O

AU - Robinson, Louise

AU - Matthews, Fiona E

AU - Brayne, Carol

AU - Richardson, Kathryn

N1 - © The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] Funding: This work was supported by the Alzheimer’s Society UK [AS-PG-2013-017].

PY - 2020/10/23

Y1 - 2020/10/23

N2 - BACKGROUND: the long-term effect of the use of drugs with anticholinergic activity on cognitive function remains unclear.METHODS: we conducted a systematic review and meta-analysis of the relationship between anticholinergic drugs and risk of dementia, mild cognitive impairment (MCI) and cognitive decline in the older population. We identified studies published between January 2002 and April 2018 with ≥12 weeks follow-up between strongly anticholinergic drug exposure and the study outcome measurement. We pooled adjusted odds ratios (OR) for studies reporting any, and at least short-term (90+ days) or long-term (365+ days) anticholinergic use for dementia and MCI outcomes, and standardised mean differences (SMD) in global cognition test scores for cognitive decline outcomes. Statistical heterogeneity was measured using the I2 statistic and risk of bias using ROBINS-I.RESULTS: twenty-six studies (including 621,548 participants) met our inclusion criteria. 'Any' anticholinergic use was associated with incident dementia (OR 1.20, 95% confidence interval [CI] 1.09-1.32, I2 = 86%). Short-term and long-term use were also associated with incident dementia (OR 1.23, 95% CI 1.17-1.29, I2 = 2%; and OR 1.50, 95% CI 1.22-1.85, I2 = 90%). 'Any' anticholinergic use was associated with cognitive decline (SMD 0.15; 95% CI 0.09-0.21, I2 = 3%) but showed no statistically significant difference for MCI (OR 1.24, 95% CI 0.97-1.59, I2 = 0%).CONCLUSIONS: anticholinergic drug use is associated with increased dementia incidence and cognitive decline in observational studies. However, a causal link cannot yet be inferred, as studies were observational with considerable risk of bias. Stronger evidence from high-quality studies is needed to guide the management of long-term use.

AB - BACKGROUND: the long-term effect of the use of drugs with anticholinergic activity on cognitive function remains unclear.METHODS: we conducted a systematic review and meta-analysis of the relationship between anticholinergic drugs and risk of dementia, mild cognitive impairment (MCI) and cognitive decline in the older population. We identified studies published between January 2002 and April 2018 with ≥12 weeks follow-up between strongly anticholinergic drug exposure and the study outcome measurement. We pooled adjusted odds ratios (OR) for studies reporting any, and at least short-term (90+ days) or long-term (365+ days) anticholinergic use for dementia and MCI outcomes, and standardised mean differences (SMD) in global cognition test scores for cognitive decline outcomes. Statistical heterogeneity was measured using the I2 statistic and risk of bias using ROBINS-I.RESULTS: twenty-six studies (including 621,548 participants) met our inclusion criteria. 'Any' anticholinergic use was associated with incident dementia (OR 1.20, 95% confidence interval [CI] 1.09-1.32, I2 = 86%). Short-term and long-term use were also associated with incident dementia (OR 1.23, 95% CI 1.17-1.29, I2 = 2%; and OR 1.50, 95% CI 1.22-1.85, I2 = 90%). 'Any' anticholinergic use was associated with cognitive decline (SMD 0.15; 95% CI 0.09-0.21, I2 = 3%) but showed no statistically significant difference for MCI (OR 1.24, 95% CI 0.97-1.59, I2 = 0%).CONCLUSIONS: anticholinergic drug use is associated with increased dementia incidence and cognitive decline in observational studies. However, a causal link cannot yet be inferred, as studies were observational with considerable risk of bias. Stronger evidence from high-quality studies is needed to guide the management of long-term use.

KW - anticholinergics

KW - cognition

KW - dementia

KW - meta-analysis

KW - older people

KW - systematic review

UR - https://academic.oup.com/ageing/article/doi/10.1093/ageing/afaa090/5864119

UR - http://www.scopus.com/inward/record.url?scp=85094685270&partnerID=8YFLogxK

U2 - 10.1093/ageing/afaa090

DO - 10.1093/ageing/afaa090

M3 - Article

C2 - 32603415

SN - 0002-0729

VL - 49

SP - 939

EP - 947

JO - Age and Ageing

JF - Age and Ageing

IS - 6

ER -

Anticholinergic drugs and incident dementia, mild cognitive impairment and cognitive decline: a meta-analysis

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