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Associations Between Midlife Anticholinergic Medication Use and Subsequent Cognitive Decline: A British Birth Cohort Study

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Abstract

Background

Anticholinergic medication use is associated with cognitive decline and incident dementia. Our study, a prospective birth cohort analysis, aimed to determine if repeated exposure to anticholinergic medications was associated with greater decline, and whether decline was reversed with medication reduction.

Methods

From the Medical Research Council (MRC) National Survey of Health and Development, a British birth cohort with all participants born in a single week of March 1946, we quantified anticholinergic exposure between ages 53 and 69 years using the Anticholinergic Cognitive Burden Scale (ACBS). We used multinomial regression to estimate associations with global cognition, quantified by the Addenbrooke’s Cognitive Examination, 3rd Edition (ACE-III). Longitudinal associations between ACBS and cognitive test results (Verbal memory quantified by the Word Learning Test [WLT], and processing speed quantified by the Timed Letter Search Task [TLST]) at three time points (age 53, 60–64 and 69) were assessed using mixed and fixed effects linear regression models. Analyses were adjusted for sex, childhood cognition, education, chronic disease count and severity, and mental health symptoms.

Results

Anticholinergic exposure was associated cross-sectionally with lower ACE-III scores at age 69, with the greatest effects in those with high exposure at ages 60–64 (mean difference − 2.34, 95% confidence interval [CI] − 3.51 to − 1.17). Longitudinally, both mild-moderate and high ACBS scores were linked to lower WLT scores, again with high exposure showing larger effects (mean difference with contemporaneous exposure − 0.90, 95% CI − 1.63 to − 0.17; mean difference with lagged exposure − 1.53, 95% CI − 2.43 to − 0.64). Associations remained in fixed effects models (mean difference with contemporaneous exposure −1.78, 95% CI −2.85 to − 0.71; mean difference with lagged exposure − 2.23, 95% CI − 3.33 to − 1.13). Associations with TLST were noted only in isolated contemporaneous exposure (mean difference − 13.14, 95% CI − 19.04 to − 7.23; p < 0.01).

Conclusions

Anticholinergic exposure throughout mid and later life was associated with lower cognitive function. Reduced processing speed was associated only with contemporaneous anticholinergic medication use, and not historical use. Associations with lower verbal recall were evident with both historical and contemporaneous use of anticholinergic medication, and associations with historical use persisted in individuals even when their anticholinergic medication use decreased over the course of the study.

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Acknowledgements

We thank National Survey of Health and Development (NSHD) study members for their lifelong participation, and past and present members of the NSHD study team who helped to collect the data. The abstract for provisional findings from this paper was previously accepted for oral presentation at the European Geriatric Medicine Society Congress 2022 in London, UK (LBO-07 in Abstracts of the 18th Congress of the European Geriatric Medicine Society. Eur Geriatr Med 13 (Suppl 1), 1–439 (2022). https://doi.org/10.1007/s41999-022-00711-8).

Author information

Authors and Affiliations

  1. MRC Unit for Lifelong Health and Ageing at UCL, London, UK

    Mark J. Rawle, Praveetha Patalay, Marcus Richards & Daniel Davis

  2. Academic Centre for Healthy Ageing (ACHA) @ Whipps Cross University Hospital, Barts Health NHS Trust, Whipps Cross Road, London, E11 1NR, UK

    Mark J. Rawle

  3. Research Department of Practice and Policy, School of Pharmacy, UCL, London, UK

    Wallis C. Y. Lau

  4. Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS Foundation Trust, London, UK

    Wallis C. Y. Lau

  5. Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, Centre for Safe Medication Practice and Research, The University of Hong Kong, Pok Fu Lam, Hong Kong

    Wallis C. Y. Lau

  6. Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Pak Shek Kok, Hong Kong

    Wallis C. Y. Lau

  7. Institute of Health Informatics and Health Data Research UK, UCL, London, UK

    Arturo Gonzalez-Izquierdo

  8. Institute of Applied Health Research, University of Birmingham, Birmingham, UK

    Arturo Gonzalez-Izquierdo

Authors
  1. Mark J. Rawle
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Corresponding author

Correspondence to Mark J. Rawle.

Ethics declarations

Sponsor’s role

No financial sponsors played any role in the design, execution, analysis and interpretation of data or writing of this study.

Funding

There was no direct funding for this project. The NSHD is funded by the Medical Research Council (MRC) (MC_UU_10019/1, MC_UU_10019/3).

Conflict of interest

The authors have no conflicts.

Ethics approval

Ethical approval for the NSHD data collection at age 68–69 was obtained from the Queen Square Research Ethics Committee (14/LO/1073) and the Scotland A Research Ethics Committee (14/SS/1009). At each stage of data collection, all participants provided written informed consent.

Consent to participate

All participants provided written informed consent for participation during recruitment into the NSHD and for all ongoing data collections.

Consent for publication

Not applicable (anonymised study).

Availability of data and material

Data and code are available on request to the NSHD Data Sharing Committee. NSHD data sharing policies and processes meet the requirements and expectations of the UK MRC policy on sharing of data from population and patient cohorts. Data requests should be submitted to rclha.swiftinfo@ucl.ac.uk; further details can be found at http://www.nshd.mrc.ac.uk/data.aspx. These policies and processes are in place to ensure that the use of data from this national birth cohort study is within the bounds of consent given previously by study members, complies with MRC guidance on ethics and research governance, and meets rigorous MRC data security standards.

Code availability

All code was compiled using Stata MP Version 17 (64-bit), and is available on GitHub (https://github.com/orgs/Lifelong-Health-Ageing/repositories).

Author contributions

MJR was responsible for data analysis, with additional input from DD. MJR devised the research question and wrote the first draft of the manuscript. MR, PP, AGI and WL provided additional statistical and methodological input. All authors contributed to interpreting the data and writing the final paper.

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Rawle, M.J., Lau, W.C.Y., Gonzalez-Izquierdo, A. et al. Associations Between Midlife Anticholinergic Medication Use and Subsequent Cognitive Decline: A British Birth Cohort Study. Drugs Aging (2024). https://doi.org/10.1007/s40266-024-01116-x

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