Cognitive Risks of Anticholinergics in the Elderly
Cognitive Risks of Anticholinergics in the Elderly
The quantification of anticholinergic burden remains a challenging task. Clinical monitoring of anticholinergic adverse effects is limited to the use of clinical instruments that classify drugs categorically according to their degree of anticholinergicity. Moreover, we are only aware of one established research method that exists – the serum anticholinergic assay – that measures anticholinergic drug exposure by quantifying serum anticholinergic activity. We describe these methods below.
There are a few research and clinical tools available for anticholinergic drug monitoring. One such tool is the Anticholinergic Drug Scale (ADS), which was developed to help clinicians identify and quantify anticholinergic burden in a clinically meaningful way. The ADS rates the anticholinergic potential of drugs on a four-point scale from 'no known' anticholinergic activity to 'marked' anticholinergic activity. Scores of all medications are summed to determine a total score.
The ADS has been shown to be correlated with peripheral markers of anticholinergic activity, that is, serum anticholinergic activity and salivation. In a randomized controlled trial of frail, elderly nursing home residents, although there was no clear linear relationship between increased ADS score and anticholinergic adverse effects, the greatest improvement in cognitive functioning was observed in patients whose ADS scores were reduced to zero. This suggests that even a minimal amount of anticholinergic activity may contribute to cognitive impairment. A limitation of scales implemented to monitor drugs with anticholinergic properties for research studies is that the drugs selected for inclusion are often limited to the population being investigated. More longitudinal research is required to determine the clinical effectiveness of active anticholinergic drug monitoring.
Despite limited availability, the measurement of serum anticholinergic activity (SAA) is still the gold standard for quantifying anticholinergic load. The serum anticholinergic radioreceptor assay measures the total antimuscarinic activity of all substances (both foreign and endogenous) present in an individual's serum. Substances in the serum with anticholinergic affinity compete with quinuclidinyl benzilate, a potent anticholinergic compound, for binding to muscarinic receptors of a prepared rat forebrain. SAA is measured in terms of atropine equivalents (pmol/ml) and ranges from the lowest detectable limit of 0.25 pmol/ml to 25.00 pmol/ml. Chew et al. measured the anticholinergic activity of 107 commonly used medications.
In addition to its lack of clinical availability, the quantitative relationship between SAA and anticholinergic adverse effects is poorly understood. Moreover, the assay lacks specificity for muscarinic receptor subtypes and it is a measure of peripheral anticholinergic levels (for an in-depth critical appraisal of the utility and limitations of the serum anticholinergic assay in research and clinical practice see Carnahan et al.). For these reasons, clinicians must rely on clinical instruments or consensus guidelines to monitor patients' anticholinergic load, despite their limitations. See Table 1 for a list of commonly prescribed medications with anticholinergic properties.
Anticholinergic Monitoring: Mitigating the Risk
The quantification of anticholinergic burden remains a challenging task. Clinical monitoring of anticholinergic adverse effects is limited to the use of clinical instruments that classify drugs categorically according to their degree of anticholinergicity. Moreover, we are only aware of one established research method that exists – the serum anticholinergic assay – that measures anticholinergic drug exposure by quantifying serum anticholinergic activity. We describe these methods below.
Clinical Instruments
There are a few research and clinical tools available for anticholinergic drug monitoring. One such tool is the Anticholinergic Drug Scale (ADS), which was developed to help clinicians identify and quantify anticholinergic burden in a clinically meaningful way. The ADS rates the anticholinergic potential of drugs on a four-point scale from 'no known' anticholinergic activity to 'marked' anticholinergic activity. Scores of all medications are summed to determine a total score.
The ADS has been shown to be correlated with peripheral markers of anticholinergic activity, that is, serum anticholinergic activity and salivation. In a randomized controlled trial of frail, elderly nursing home residents, although there was no clear linear relationship between increased ADS score and anticholinergic adverse effects, the greatest improvement in cognitive functioning was observed in patients whose ADS scores were reduced to zero. This suggests that even a minimal amount of anticholinergic activity may contribute to cognitive impairment. A limitation of scales implemented to monitor drugs with anticholinergic properties for research studies is that the drugs selected for inclusion are often limited to the population being investigated. More longitudinal research is required to determine the clinical effectiveness of active anticholinergic drug monitoring.
Serum Anticholinergic Assay
Despite limited availability, the measurement of serum anticholinergic activity (SAA) is still the gold standard for quantifying anticholinergic load. The serum anticholinergic radioreceptor assay measures the total antimuscarinic activity of all substances (both foreign and endogenous) present in an individual's serum. Substances in the serum with anticholinergic affinity compete with quinuclidinyl benzilate, a potent anticholinergic compound, for binding to muscarinic receptors of a prepared rat forebrain. SAA is measured in terms of atropine equivalents (pmol/ml) and ranges from the lowest detectable limit of 0.25 pmol/ml to 25.00 pmol/ml. Chew et al. measured the anticholinergic activity of 107 commonly used medications.
In addition to its lack of clinical availability, the quantitative relationship between SAA and anticholinergic adverse effects is poorly understood. Moreover, the assay lacks specificity for muscarinic receptor subtypes and it is a measure of peripheral anticholinergic levels (for an in-depth critical appraisal of the utility and limitations of the serum anticholinergic assay in research and clinical practice see Carnahan et al.). For these reasons, clinicians must rely on clinical instruments or consensus guidelines to monitor patients' anticholinergic load, despite their limitations. See Table 1 for a list of commonly prescribed medications with anticholinergic properties.
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