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

Abstract

IntroductionStudies 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 MethodsA 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.ResultsThe 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).ConclusionThis 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.

Preoperative medication use and postoperative delirium: a systematic review

“…The most important mechanism involves disturbances of the neurotransmitter system; comprising of insufficient acetylcholine activity, increase in dopamine and noradrenaline activities, and either an excess or shortage of serotonin and gamma-aminobutyric acid (GABA) activities [ 1 ]. The acetylcholine hypothesis has been supported by studies showing an increase in the occurrence of delirium in patients with higher level of serum anticholinergic activity [ 2 ].…”

Association between using medications with anticholinergic properties and short‐term cognitive decline among older men: A retrospective cohort study in Taiwan

“…A great number of commonly prescribed drugs, such as antipsychotics, antidepressants, antihypertensive agents, antispasmodics and antihistamines, have been shown to possess anticholinergic activities. The use of anticholinergic drugs has been strongly associated with adverse health outcomes, including cognitive impairment, dementia, falls, functional decline, hospitalization and mortality, especially in older adults . With advanced aging, people can become more susceptible to anticholinergic adverse effects as a result of: (i) the decreased level of acetylcholine synthesis or the decreased number of acetylcholine receptors, leading to increased pharmacodynamics sensitivity; (ii) the reduction in hepatic metabolism and renal excretion and (iii) higher blood–brain barrier permeability, allowing more anticholinergic drugs crossing into the brain .…”

“…The use of anticholinergic drugs has been strongly associated with adverse health outcomes, including cognitive impairment, dementia, falls, functional decline, hospitalization and mortality, especially in older adults. [4][5][6][7] With advanced aging, people can become more susceptible to anticholinergic adverse effects as a result of: (i) the decreased level of acetylcholine synthesis or the decreased number of acetylcholine receptors, leading to increased pharmacodynamics sensitivity; 8 (ii) the reduction in hepatic metabolism and renal excretion 9 and (iii) higher blood-brain barrier permeability, allowing more anticholinergic drugs crossing into the brain. 10 Therefore, the American Geriatrics Society Beers criteria constantly recommended avoid using medications with anticholinergic effects for older people.…”

An anticholinergic burden score for German prescribers: score development

“…Tools were excluded because the scoring system was not comparable to the other tools [ 33 , 36 ], the tool was outdated, [ 35 ] there was an updated version published [ 32 ], or the scoring was solely based on serum assays [ 25 ]. Literature reviews and meta-analysis failed to show an association of serum anticholinergic activity and anticholinergic effects [ 37 ], whereas there is an association shown for anticholinergic drug scores mainly based on expert opinion [ 8 – 12 , 27 ]. To avoid missing relevant tools, the excluded articles were reviewed regarding more tools as they all evaluated the association of anticholinergic drugs and negative outcomes in patients [ 9 , 19 , 27 , 38 , 39 ].…”