**3. Assessment of anticholinergic burden**

The effects of anticholinergic agents are cumulative and there are various tools available to help evaluate the degree of 'cholinergic burden' in an older adult's drug regimen. Early work by Tune et al. resulted in the development of the serum anticholinergic assay, a biologic measure intended to quantify anticholinergic drug burden [5]. Using this assay, it has been shown that many drugs taken by older adults have high serum anticholinergic activity **Table 1** [6].

Over 600 medications have some degree of anticholinergic activity [7]. One drawback of using the serum anticholinergic assay is that it may not be readily available in clinical settings and even if available, there can be a delay in care pending interpretation of results [8].

As a result of these limitations, scales have been developed to easily calculate the cumulative anticholinergic burden. The Anticholinergic Cognitive Burden Scale (ACBS) rates drugs on a scale of 0 (no anticholinergic effect) to 3 with 1 representing a possible anticholinergic effect based on laboratory tests but no evidence of clinically relevant cognitive effects and scores of 2 or 3 indicating definite anticholinergic effects. Higher scores indicate greater anticholinergic burden and warrant a re-evaluation of the drug regimen. The presence of a drug scoring 2 or 3 can increase the risk of cognitive impairment by 46% over 6 years. Further, each point increase in the ACBS has been associated with a decrease in the Mini-Mental Examination Score of 0.33 points over the course of 2 years. This point increase has also been associated with a 26% increase in the risk of death [9].

Another tool is the Anticholinergic Risk Scale (ARS). Similar to ACBS, the ARS is also a 3-point scale. The developers of the scale assessed whether the ARS could predict the risk of anticholinergic adverse effects in a geriatric evaluation and management (GEM) group and in a primary care (PC) group. The investigators found that in the GEM group, older adults experienced more adverse CNS effects whereas in the PC group, more elderly had peripheral adverse effects [10].

The Anticholinergic Drug Scale (ADS), which was previously known as the Clinician-Rated Anticholinergic Scale, is another 3-point scale. It includes the


#### **Table 1.**

*Anticholinergic drug level of medications commonly used by older adults.*

largest number of anticholinergic agents. A score of 0 indicates no known anticholinergic properties; a score of 1 means that the drug has the potential for anticholinergic activity as evidenced by receptor binding sites; a score of 2 represents a drug that causes anticholinergic adverse effects at higher doses; and a score of 3 represents a drug with marked anticholinergic activity [11].

The Anticholinergic Burden Classification (ABC) measures serum anticholinergic activity but takes into account the duration of exposure, adjusts for mode of administration (i.e., topical, nasal, oral, etc.), assesses for possible drug–drug interactions and for the ability of drugs to cross the blood brain barrier [12].

The Anticholinergic Activity Scale (AAS) is based on *in vivo* radioreceptor assay determinations and ranks drugs on five levels: 0 (no anticholinergic activity); 0/+ (no or minimal anticholinergic activity); + (low anticholinergic activity), ++ (moderate anticholinergic activity), and +++ (high anticholinergic activity) [13].

The Anticholinergic Loading Scale (ALS) is a tool used in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study that calculates anticholinergic load. Anticholinergic load was found to have an adverse effect on psychomotor speed and executive function in healthy controls [14].

The Anticholinergic Effect on Cognition Scale (AECS) is another 3-point scale that uses *in vitro* anticholinergic potency as well as a drug's ability to cross the blood brain barrier [15].

Unlike the previous scales, which only focus on the anticholinergic potential of a drug regimen, the Drug Burden Index (DBI) takes into account anticholinergic effects, sedative effects of medications, and the total number of medications. It measures the effect of cumulative exposure to both anticholinergic and sedative medications on physical and cognitive function in older adults. This scale is based on the *minimum recommended daily doses* of each drug. Drugs that have both anticholinergic and sedative properties are classified based on their anticholinergic effects [16]. The developers studied this scale in over 3000 healthy communitydwelling older adults aged 70–79 years. They found that the use of anticholinergic and sedative medications was associated with poorer physical performance and cognitive performance. Each unit of drug burden on physical function was equal to having three additional physical comorbidities whereas each unit of drug burden on cognition was similar to having four additional physical comorbidities or about half of the effects of anxiety, depression or cognitive impairment [17].

A recent publication compared several of the anticholinergic scales providing a description of the tool and listing the number of drugs with anticholinergic activity that are included in the scale [18]. However, while many of these scales have shown a significant correlation between anticholinergic burden assessment and serum anticholinergic drug levels, they have limitations. There is currently no 'gold standard' to identify an *anticholinergic drug*. Only parent compounds are included in these scales, therefore, there is no information on active metabolites that may also contribute to the anticholinergic burden. While some scales do take dose into the account, this is not consistently done in all tools. These scales also assume that there is a linear relationship between anticholinergic levels and toxicity. Lastly, serum anticholinergic activity assays do not distinguish between agonist versus antagonist binding of the cholinergic receptors [19].
