Serum Anticholinergic Activity and Cognitive and Functional Adverse Outcomes in Older People: A Systematic Review and Meta-Analysis of the Literature

Abstract

Introduction: Studies have reported associations between serum anticholinergic activity (SAA) and decline in cognitive performance, delirium, and functional impairment. The aim of this meta-analysis was to explore and quantify associations between SAA and adverse cognitive and functional outcomes in older people.

Materials and methods: A literature search in Ovid MEDLINE, EMBASE, PsycINFO and IPA from 1946-2014 was completed. The primary outcomes of interest were cognitive and functional adverse outcomes associated with SAA in older people aged 55 years and above. The Cochrane Risk-Bias assessment tool was used to assess bias in randomised controlled trials (RCTs). The Newcastle-Ottawa Scale was used to assess the quality of non-RCTs. Meta-analyses were conducted for RCTs and cohort studies separately. Heterogeneity was assessed using I2 tests.

Results: The primary electronic literature search identified a total of 1559 records in the 4 different databases. On the basis of full-text analysis, 33 studies that met the inclusion criteria. The review included 4 RCTs, 5 prospective cohort studies, 3 longitudinal cohort studies, 17 cross-sectional studies, and 4 case-control studies. Twenty-four of the retrieved studies examined an association between SAA and cognitive outcomes, 2 studies examined an association with SAA and functional outcomes and 8 studies examined associations between SAA and both cognitive, and functional outcomes. The meta-analysis on 4 RCTs showed no association with higher SAA and cognitive performance (I2 = 89.38%, H2 = 25.53 and p-value = <0.05) however, the pooled data from 4 observational studies showed elevated SAA was associated with reduced cognitive performance (I2 = 0.00%, H2 = 3.37 and p-value = 0.34).

Conclusion: This systematic review summarises the limitations of the SAA on predicting cognitive and functional outcomes in older people. SAA measured by receptor bioassay is flawed and its use in older people with multimorbidity and polypharmacy is questionable.

Fig 1. PRISMA flow diagram of study selection process.

Fig 2

(a and b) Forest plot of standardised mean difference between increased SAA and a reduced MMSE score (positive favours MMSE reduction). Forest plot, using data from (a) 4 observational studies and (b) 4 randomised controlled trails following interventions that increase SAA and a decline in MMSE score. A) The result support SAA lowers the MMSE score (p < 0.05) for observational studies. B) The result did not support a conclusion that SAA lowers the MMSE score (p = 0.5) for RCTs.