Effects of Medications With Anti-Cholinergic Properties
Abstract and Introduction
Objectives: To determine the effect of drugs with anti-cholinergic properties on relevant health outcomes.
Design: Electronic published and unpublished literature/trial registries were systematically reviewed. Studies evaluating medications with anti-cholinergic activity on cognitive function, delirium, physical function or mortality were eligible.
Results: Forty-six studies including 60,944 participants were included. Seventy-seven percent of included studies evaluating cognitive function (n = 33) reported a significant decline in cognitive ability with increasing anti-cholinergic load (P < 0.05). Four of five included studies reported no association with delirium and increasing anti-cholinergic drug load (P > 0.05). Five of the eight included studies reported a decline in physical function in users of anti-cholinergics (P < 0.05). Three of nine studies evaluating mortality reported that the use of drugs with anti-cholinergic properties was associated with a trend towards increased mortality, but this was not statistically significant. The methodological quality of the evidence-base ranged from poor to very good.
Conclusion: Medicines with anti-cholinergic properties have a significant adverse effect on cognitive and physical function, but limited evidence exists for delirium or mortality outcomes.
Drugs with anti-cholinergic properties are commonly prescribed for a variety of medical illnesses. With a globally ageing population, much of this drug burden falls on the elderly. Ninety percent of older adults report taking at least one prescription medication. It has been estimated that 20–50% of older people have been prescribed at least one medication with anti-cholinergic activity. Younger adults may also be prescribed long-term anti-cholinergic treatment for conditions such as asthma or to manage the side-effects of medicines used to treat psychiatric disorders. It has been recommended that increased care should be taken to avoid the inappropriate prescribing of anti-cholinergic drugs due to the wide spectrum of central effects such as the onset of dizziness, sedation, confusion, in addition to increasing delirium, causing a decline in cognitive and physical function. Peripheral adverse effects are also commonly reported and include dry mouth, dry eyes, constipation, blurred vision and increased heart rate.
Much of the previous evidence has focused on a link between medications with anti-cholinergic properties and cognitive function. Medications with anti-cholinergic properties recognized by the anti-cholinergic cognitive burden (ACB) scale have been recently correlated with an additional 0.33 point decline in Mini-Mental State Examination (MMSE) score over 2 years, a 2-fold increase in cognitive impairment with as little as 60–90 days of use, and ~50–80% increase in the risk of incident cognitive impairment over 6 years.
A decline in cognitive function and the diagnosis of mild cognitive impairment is associated with a progression to dementia within 5 years, making primary prevention and avoidance of anti-cholinergic medications wherever possible, of significant importance as a strategy to protect against persistent cognitive decline. Similarly, it is well known that functional impairment in older adults limits independent living and impacts on their quality of life. Mild cognitive impairment has also been attributed to an increased risk of falls, further increasing morbidity and reduced physical function in older people.
This systematic review assesses the empirical research surrounding the effect of increasing anti-cholinergic load on cognitive function, delirium, physical function and mortality. To the author's knowledge, this is the first systematic review to evaluate the association between medications with anti-cholinergic properties and delirium or physical function. This paper will also provide an important update required to review the current literature on a possible association with cognitive function and mortality.