CoChat
Sign Up
Cited by 53Pharmaceutical Practices and Patient OutcomesIntensive Care Unit Cognitive DisordersDementia and Cognitive Impairment Research

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

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

Open access
Salahudeen, Mohammed Saji, Chyou, Te-yuan, Nishtala, Prasad S.·2016·PLOS ONE
DOI 10.1371/journal.pone.0151084PMC PMC4801377
Open this paper in CoChat — free account

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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0151084

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Serum anticholinergic activity measured by a receptor bioassay does not correlate well with effects on cognition.

    “Serum anticholinergic activity measured by a receptor bioassay does not correlate well with effects on cognition,16 28”

    From Anticholinergic drugs and risk of dementia: case-control study (2018) · cites this paper as [28]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 61

  1. MS Salahudeen, 2015, Comparison of anticholinergic risk scales and associations with adverse health outcomes in older people, J Am Geriatr Soc, 63, 85, 10.1111/jgs.13206 · DOI · Paper page
  2. CM Roe, 2002, Use of anticholinergic medications by older adults with dementia, J Am Geriatr Soc, 50, 836, 10.1046/j.1532-5415.2002.50208.x · DOI
  3. LE Tune, 2001, Anticholinergic effects of medication in elderly patients, J Clin Psychiatry, 62, 11
  4. MS Salahudeen, 2014, Impact of anticholinergic discontinuation on cognitive outcomes in older people: a systematic review, Drugs Aging, 31, 185, 10.1007/s40266-014-0158-4 · DOI
  5. MS Salahudeen, 2015, The Influence of Patient Characteristics on Anticholinergic Events in Older People, Dement Geriatr Cogn Dis Extra, 5, 530, 10.1159/000441718 · DOI
  6. L Tune, 1980, Serum levels of anticholinergic drugs in treatment of acute extrapyramidal side effects, Arch Gen Psychiatry, 37, 293, 10.1001/archpsyc.1980.01780160063007 · DOI
  7. BH Mulsant, 2003, Serum anticholinergic activity in a community-based sample of older adults: relationship with cognitive performance, Arch Gen Psychiatry, 60, 198, 10.1001/archpsyc.60.2.198 · DOI
  8. ML Chew, 2005, Serum anticholinergic activity and cognition in patients with moderate-to-severe dementia, Am J Geriatr Psychiatry, 13, 535, 10.1097/00019442-200506000-00013 · DOI
  9. ML Chew, 2008, Anticholinergic activity of 107 medications commonly used by older adults, J Am Geriatr Soc, 56, 1333, 10.1111/j.1532-5415.2008.01737.x · DOI
  10. JR Mach Jr, 1995, Serum anticholinergic activity in hospitalized older persons with delirium: A preliminary study, J Am Geriatr Soc, 43, 491, 10.1111/j.1532-5415.1995.tb06094.x · DOI
  11. PS Miller, 1988, Association of low serum anticholinergic levels and cognitive impairment in elderly presurgical patients, Am J Psychiatry, 145, 342, 10.1176/ajp.145.3.342 · DOI
  12. OJ Thienhaus, 1990, Anticholinergic serum levels and cognitive performance, Eur Arch Psychiatry Clin Neurosci, 240, 28, 10.1007/BF02190089 · DOI
  13. GD Tollefson, 1991, The relationship of serum anticholinergic activity to mental status performance in an elderly nursing home population, J Neuropsychiatry Clin Neurosci, 3, 314, 10.1176/jnp.3.3.314 · DOI
  14. BW Rovner, 1988, Self-care capacity and anticholinergic drug levels in nursing home patients, Am J Psychiatry, 145, 107, 10.1176/ajp.145.1.107 · DOI
  15. PS Nishtala, 2009, Anticholinergic activity of commonly prescribed medications and neuropsychiatric adverse events in older people, J Clin Pharmacol, 49, 1176, 10.1177/0091270009345690 · DOI
  16. LO Watne, 2014, Anticholinergic activity in cerebrospinal fluid and serum in individuals with hip fracture with and without delirium, J Am Geriatr Soc, 62, 94, 10.1111/jgs.12612 · DOI
  17. P Lampela, 2013, Anticholinergic drug use, serum anticholinergic activity, and adverse drug events among older people: a population-based study, Drugs Aging, 30, 321, 10.1007/s40266-013-0063-2 · DOI
  18. C Thomas, 2008, Serum anticholinergic activity and cerebral cholinergic dysfunction: An EEG study in frail elderly with and without delirium, BMC Neurosci, 9, 86, 10.1186/1471-2202-9-86 · DOI
  19. P Gerretsen, 2011, Drugs with anticholinergic properties: a current perspective on use and safety, Expert Opin Drug Saf, 10, 751, 10.1517/14740338.2011.579899 · DOI
  20. RM Carnahan, 2002, A critical appraisal of the utility of the serum anticholinergic activity assay in research and clinical practice, Psychopharmacol Bull, 36, 24
  21. EA Cox, 2009, Flaws in the serum anticholinergic activity assay: Implications for the study of delirium, J Am Geriatr Soc, 57, 1707, 10.1111/j.1532-5415.2009.02411.x · DOI
  22. P Lampela, 2015, Central Anticholinergic Adverse Effects and Their Measurement, Drugs Aging
  23. RD Nebes, 2007, Serum anticholinergic activity and motor performance in elderly persons, J Gerontol A Biol Sci Med Sci, 62A, 83, 10.1093/gerona/62.1.83 · DOI
  24. AJ Remillard, 1994, A pilot project to assess the association of anticholinergic symptoms with anticholinergic serum levels in the elderly, Pharmacotherapy, 14, 482, 10.1002/j.1875-9114.1994.tb02840.x · DOI
  25. KA Bottiggi, 2006, Long-term cognitive impact of anticholinergic medications in older adults, Am J Geriatr Psychiatry, 14, 980, 10.1097/01.JGP.0000224619.87681.71 · DOI
  26. F Landi, 2007, Anticholinergic drugs and physical function among frail elderly population, Clin Pharmacol Ther, 81, 235, 10.1038/sj.clpt.6100035 · DOI
  27. LE Tune, 1982, Serum levels of anticholinergic drugs and impaired recent memory in chronic schizophrenic patients, Am J Psychiatry, 139, 1460, 10.1176/ajp.139.11.1460 · DOI
  28. FM Mondimore, 1983, Post-ECT confusional states associated with elevated serum anticholinergic levels, Am J Psychiatry, 140, 930, 10.1176/ajp.140.7.930 · DOI
  29. S Brecht, 2007, Serum anticholinergic activity in patients following cardiac surgery and healthy individuals following amitriptyline application, Methods Find Exp Clin Pharmacol, 29, 223, 10.1358/mf.2007.29.3.1075357 · DOI
  30. S Vinogradov, 2009, The cognitive cost of anticholinergic burden: decreased response to cognitive training in schizophrenia, Am J Psychiatry, 166, 1055, 10.1176/appi.ajp.2009.09010017 · DOI
  31. L Tune, 1992, Anticholinergic effects of drugs commonly prescribed for the elderly: potential means for assessing risk of delirium, Am J Psychiatry, 149, 1393, 10.1176/ajp.149.10.1393 · DOI
  32. RM Carnahan, 2006, The anticholinergic drug scale as a measure of drug-related anticholinergic burden: Associations with serum anticholinergic activity, J Clin Pharmacol, 46, 1481, 10.1177/0091270006292126 · DOI
  33. ML Ancelin, 2006, Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study, BMJ, 332, 455, 10.1136/bmj.38740.439664.DE · DOI · Paper page
  34. K Plaschke, 2007, Significant correlation between plasma and CSF anticholinergic activity in presurgical patients, Neurosci Lett, 417, 16, 10.1016/j.neulet.2007.02.015 · DOI
  35. TE Lackner, 2008, Randomized, placebo-controlled trial of the cognitive effect, safety, and tolerability of oral extended-release oxybutynin in cognitively impaired nursing home residents with urge urinary incontinence, J Am Geriatr Soc, 56, 862, 10.1111/j.1532-5415.2008.01680.x · DOI
  36. H Kersten, 2013, Cognitive effects of reducing anticholinergic drug burden in a frail elderly population: A randomized controlled trial, J Gerontol A Biol Sci Med Sci, 68A, 271, 10.1093/gerona/gls176 · DOI · Paper page
  37. LE Tune, 1981, Association of postoperative delirium with raised serum levels of anticholinergic drugs, Lancet, 2, 651, 10.1016/S0140-6736(81)90994-6 · DOI
  38. AJ Remillard, 1994, Pilot project to assess the association of anticholinergic symptoms with anticholinergic serum levels in the elderly, Pharmacotherapy, 14, 482, 10.1002/j.1875-9114.1994.tb02840.x · DOI
  39. K Plaschke, 2007, EEG changes and serum anticholinergic activity measured in patients with delirium in the intensive care unit, Anaesthesia, 62, 1217, 10.1111/j.1365-2044.2007.05255.x · DOI
  40. A Rossi, 2014, Serum anticholinergic activity and postoperative cognitive dysfunction in elderly patients, Anesth Analg, 119, 947, 10.1213/ANE.0000000000000390 · DOI
  41. RC Golinger, 1987, Association of elevated plasma anticholinergic activity with delirium in surgical patients, Am J Psychiatry, 144, 1218, 10.1176/ajp.144.9.1218 · DOI
  42. BC van Munster, 2012, Longitudinal assessment of serum anticholinergic activity in delirium of the elderly, J Psychiatr Res, 46, 1339, 10.1016/j.jpsychires.2012.06.015 · DOI
  43. M Kashyap, 2015, Small longitudinal study of serum anticholinergic activity and cognitive change in community-dwelling older adults, Am J Geriatr Psychiatry, 23, 326, 10.1016/j.jagp.2014.09.009 · DOI
  44. L Tune, 1993, Association of anticholinergic activity of prescribed medications with postoperative delirium, J Neuropsychiatry Clin Neurosci, 5, 208, 10.1176/jnp.5.2.208 · DOI
  45. RD Nebes, 1997, Low-level serum anticholinergicity as a source of baseline cognitive heterogeneity in geriatric depressed patients, Psychopharmacol Bull, 33, 715
  46. JM Flacker, 1998, The association of serum anticholinergic activity with delirium in elderly medical patients, Am J Geriatr Psychiatry, 6, 31, 10.1097/00019442-199802000-00005 · DOI
  47. JM Flacker, 1999, Serum anticholinergic activity changes with acute illness in elderly medical patients, J Gerontol A Biol Sci Med Sci, 54A, M12, 10.1093/gerona/54.1.M12 · DOI
  48. C Mussi, 1999, Importance of serum anticholinergic activity in the assessment of elderly patients with delirium, J Geriatr Psychiatry Neurol, 12, 82, 10.1177/089198879901200208 · DOI
  49. RD Nebes, 2005, Serum anticholinergic activity, white matter hyperintensities, and cognitive performance, Neurology, 65, 1487, 10.1212/01.wnl.0000183152.16690.26 · DOI
  50. K Konishi, 2010, Adverse effects of anticholinergic activity on cognitive functions in Alzheimer's disease, Psychogeriatrics, 10, 34, 10.1111/j.1479-8301.2010.00310.x · DOI
  51. RD Nebes, 2011, Cognitive slowing associated with elevated serum anticholinergic activity in older individuals is decreased by caffeine use, Am J Geriatr Psychiatry, 19, 169, 10.1097/JGP.0b013e3181e4490d · DOI
  52. K Hori, 2011, Influence of anticholinergic activity in serum on clinical symptoms of Alzheimer's disease, Neuropsychobiology, 63, 147, 10.1159/000321591 · DOI
  53. H Kersten, 2013, Higher anticholinergic drug scale (ADS) scores are associated with peripheral but not cognitive markers of cholinergic blockade. Cross sectional data from 21 Norwegian nursing homes, Br J Clin Pharmacol, 75, 842, 10.1111/j.1365-2125.2012.04411.x · DOI
  54. AA Mangoni, 2013, Measures of anticholinergic drug exposure, serum anticholinergic activity, and all-cause postdischarge mortality in older hospitalized patients with hip fractures, Am J Geriatr Psychiatry, 21, 785, 10.1016/j.jagp.2013.01.012 · DOI
  55. K Plaschke, 2010, Increased cortisol levels and anticholinergic activity in cognitively unimpaired patients, J Neuropsychiatry Clin Neurosci, 22, 433, 10.1176/jnp.2010.22.4.433 · DOI
  56. K Plaschke, 2013, The influence of preoperative serum anticholinergic activity and other risk factors for the development of postoperative cognitive dysfunction after cardiac surgery, J Thorac Cardiovasc Surg, 145, 805, 10.1016/j.jtcvs.2012.07.043 · DOI
  57. JM Flacker, 1998, The association of serum anticholinergic activity with delirium in elderly medical patients, Am J Geriatr Psychiatry, 6, 31, 10.1097/00019442-199802000-00005 · DOI
  58. RD Nebes, 2007, Serum anticholinergic activity and motor performance in elderly persons, J Gerontol A Biol Sci Med Sci, 62A, 83, 10.1093/gerona/62.1.83 · DOI
  59. N Lechevallier-Michel, 2005, Drugs with anticholinergic properties and cognitive performance in the elderly: results from the PAQUID Study, Br J Clin Pharmacol, 59, 143, 10.1111/j.1365-2125.2004.02232.x · DOI
  60. N Campbell, 2009, The cognitive impact of anticholinergics: a clinical review, Clin Interv Aging, 4, 225
  61. CV Bostock, 2010, Association between prescribing of antimuscarinic drugs and antimuscarinic adverse effects in older people, Expert Rev Clin Pharmacol, 3, 441, 10.1586/ecp.10.34 · DOI

Cited by

Sorted by citations

Metadata

Authors
Salahudeen, M. S., Chyou, T.-Y., & Nishtala, P. S.
Affiliations
University of Otago (NZ)
Corresponding author
Nishtala, Prasad S.
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2016-03-21
Volume
11
Issue
3
Pages
e0151084
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0151084
PMC
PMC4801377
OpenAlex
W2308250335
Cited by
53
References
2
Citations by year
2025: 5 · 2024: 5 · 2023: 4 · 2022: 9 · 2021: 5 · 2020: 9 · 2019: 4 · 2018: 8 · 2017: 3
FWCI
0.52
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eCite Digital Repository (University of Tasmania) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
  • Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
anticholinergic burden, older adults, cognitive decline, functional disability, delirium, polypharmacy, multimorbidity, adverse drug outcomes
MeSH terms
Aged, Aged, 80 and over, Cognition, Humans, Middle Aged, Neuropsychological Tests, Cholinergic Antagonists

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review