What are the associations between anticholinergic medication exposure and adverse health outcomes in older people living with frailty?

Talk Code: 
David Mehdizadeh
David Mehdizadeh, Dr Oliver Todd, Dr Matthew Hale, Hadar Zaman, Dr Iuri Marques, Owen Johnson, Dr Muhammad Faisal, Prof Andrew Clegg, Dr Duncan Petty
Author institutions: 
(NIHR) Yorkshire & Humber Patient Safety Translational Research Centre (NIHR YHPSTRC), University of Bradford, University of Leeds


Routine identification of older people living with frailty has become integral to primary care medicines management strategies, driven by the NHS Long Term Plan. Primary Care Networks (PCNs) will use existing tools to stratify patients by frailty severity, proactively targeting the most severe for medication reviews. A priority area is the review of anticholinergics (ACs); medicines which block the neurotransmitter acetylcholine in the brain and peripheral nervous system. They are commonly prescribed and are indicated for a range of conditions, and although they can have positive outcomes in older people, growing evidence suggests associations with cognitive and physical dysfunction, falls, hospitalisation and even death. Older people living with frailty are likely to be more susceptible to the adverse effects of AC medicines, however this has been understudied, and little is known about the extent of these associations in this syndrome. Similarly, it is unknown whether frailty severity modifies risks of outcomes when exposed to ACs. The aim of this systematic review is to identify, appraise and synthesise existing literature in this field, with a view to answering the following research question: what are the associations between AC medication exposure and adverse health outcomes in older people living with frailty?


MEDLINE, CINAHL, Embase, Web of Science, PsycINFO and The Cochrane Database of Systematic Reviews were searched, from inception to July 2019. Search terms represented three domains: 1) aged participants 2) AC medicines and 3) observational studies. Studies were selected if participants were 65 and over and exposed to ACs, deemed to be living with pre-frailty/frailty, and where clinical outcomes were measured. Screening of papers, data extraction and quality appraisal were performed by two independent reviewers. Disagreements were resolved by a third reviewer or consensus-based discussion. Citation analysis was conducted using Publish or Perish software and Web of Science.


Titles and abstracts of 12,070 unique papers were screened, identifying 61 papers for full-text review. 12 papers met the inclusion criteria and were subject to a narrative synthesis. Interim findings are that AC exposure can be associated with adverse outcomes in older people living with frailty; particularly falls, physical dysfunction and mortality, however, the risk modifying role of frailty is unclear. Inconsistencies in how studies measure AC exposure and frailty, and the lack of studies designed specifically for frail populations, impairs the generalisability of the findings.


Although early findings show some associations, there are deficiencies in research which can support reliable and clinically meaningful conclusions in this area. As frailty stratification is now embedded within medicines management strategies, it is essential that the use of ACs in this syndrome is better understood, particularly with regards to whether stratifying by frailty severity for targeted medication reviews is a clinically useful approach.

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David Mehdizadeh
Funding acknowledgement: 
This research was funded by the National Institute for Health Research (NIHR) Yorkshire and Humber Patient Safety Translational Research Centre (NIHR YHPSTRC). The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care.