Measuring anticholinergic burden and potential risk

Delirium describes a mental state which causes confusion, disorientation so that the individual may not be able to think or remember clearly. Causes include infections, medication and organ failure. 

Egberts et al. investigated the possible association between anticholinergic burden (ACB), measured with Anticholinergic Rating Scales, and delirium.¹³⁵ Studies looked at prevalence of delirium and reported an association between delirium and ACB. They concluded that the evidence suggested the anticholinergic risk scale (ARS) is a useful means for identifying people with ACB at risk of delirium. Welsh et al reviewed reported association between delirium and ACB using a range of ACB scales and found the association between adverse outcomes and anticholinergic burden varies between scores and has not been conclusively established.¹³⁶

Two SRs and a guideline (GL) reported an association between ACB and mortality. Two were judged to be low quality. The third, the SR by Ali et al. was judged acceptable.¹³⁷ They examined the reported association between ACB and mortality, specifically in older adults. Twenty-seven studies looked at the association between ACB and mortality: 15 studies (56%) reported a positive correlation between ACB and mortality. Of the ten that reported a lack of positive association, 80% had a follow-up period of one year or less.

A 2019 NHS guideline concluded there is a need to be cautious when prescribing medicines with anticholinergic effects; and proposed the need to minimise their use where possible; to be cautious when prescribing in older adults, people with frailty, or those with complex multimorbidities.¹³⁸

Medicines with anticholinergic effects are risk factors for a variety of cognitive disorders. Both the NICE guidelines on the diagnosis and management of dementia (including Alzheimer's disease)¹³³ and NICE guidance on management of urinary continence and pelvic organ prolapse in women¹³⁹ noted that those with dementia are frequently prescribed medicines with a high ACB (either through individual medicines or by combinations). This puts the individual at risk of cognitive impairment, and so NICE recommended reducing medicines associated with increased anticholinergic burden.

NICE guidance to manage urinary incontinence reported how older adults taking medications with anticholinergic effect have increased risk of cognitive impairment therefore there is a need to be cautious when prescribing medicines with anticholinergic effects. They recommended that:

• Prescribing medications with an anticholinergic effect should be minimised for older adults, people with frailty, or people with complex multimorbidities.
• Older people are at greater risk of constipation, urinary retention, dry mouth/eyes, sedation, confusion, delirium, and reduced cognition.
• If a person has a cognitive impairment/dementia, they should receive a medication review to minimise medication with ACB or identify alternatives.
• Women diagnosed with dementia, should be made aware of the risk of cognitive impairment from medication with ACB used for bladder control.

Welsh et al. reviewed a reported association between cognitive function and anticholinergic burden and found that two-thirds of the studies reported an association with ACB and impaired cognitive function.¹³⁶ Mehdizadeh et al. conducted a high-quality SR examining the association between anticholinergic exposure and cognitive dysfunction.¹⁴⁰ They reported older community-dwelling women living in the USA were at increased odds of impaired cognitive function, indicated by a MMSE score ≤ 26, but they were unable to make a definitive conclusion on whether this decline was solely attributable to medication with anticholinergic side effects.

The Cochrane Review by Taylor-Rowan et al. assessed the risk of cognitive decline/dementia from ACB.¹⁴¹ They focused on the strength of association between ACB and future cognitive decline or dementia in different healthcare settings (primary care, secondary care, or community settings); different anticholinergic burden scales; and the effect of duration of exposure and duration of follow-up on risk. They found a significant increase in the risk of cognitive impairment or dementia for those taking anticholinergic medication compared to those who do not.

They found an association between increasing ACB and risk of dementia. The review suggests that careful consideration should be made before prescribing anticholinergic medication to older adults.

Evidence highlights the association between risk of fractures and falls, and ACB.^{136,138,140,142} There is no significant change in bone mineral density (BMD).¹⁴³ The EuGMS (European Geriatric Medicine Society) group on Fall-Risk Increasing Drugs conducted a modified Delphi based on metanalysis of national fall prevention guidelines in Europe.⁸⁴ This is referred to the STOPPFall list. All of the medicines identified in this list have anticholinergic properties and these should be used to prioritise individuals for review and are shown in the table below. A person-centred approach needs to be taken in order to review the impact of anticholinergic burden score.

While anticholinergic burden does not alter frailty status,¹⁴⁰ these guidelines recommend that the anticholinergic impact, on cognitive and peripheral effects, falls, delirium and mortality, should be minimised for people with any level of frailty.