Abstract
Background
An increasing number of medications that are frequently prescribed to elderly patients have been identified as having weak but definite anticholinergic properties. Few epidemiological studies have evaluated the impact of these drugs on verbal episodic memory using sensitive and specific neuropsychological testing in an elderly population presenting with cognitive impairment.
Objectives
The aim of this study was to assess the effect of drugs with anticholinergic properties on verbal episodic memory function in elderly patients presenting for memory evaluation.
Study Design
We performed a retrospective, cross-sectional study that included 134 consecutive elderly outpatients who attended the daycare memory unit of Centre Hospitalier Sud, Lyon, France. We searched the MEDLINE database (1973–2008) to identify drugs with anticholinergic properties. All drugs with well known anticholinergic activity, mild reported anticholinergic effects or in vitro anticholinergic activity were included in the study.
Measurements
We used the Free and Cued Selective Reminding (FCSR) test to evaluate verbal episodic memory.
Results
The mean±SD number of drugs with anticholinergic properties taken by the subjects was 0.64±0.82. Fifty percent of the subjects (n = 67) had a prescription for at least one drug with anticholinergic properties and 16% (n = 21) had a prescription for two or more. Drugs with anticholinergic properties most frequently prescribed in our cohort were cardiovascular (furosemide, hydrochlorothiazide, digoxin), antidepressant (paroxetine, sertraline, fluoxetine) and antispasmodic (oxybutynin chloride) drugs. The number of drugs with anticholinergic properties that subjects were taking was associated with reduced performance on tasks that assessed verbal memory (p < 0.05). Neuropsychological test batteries revealed a significant unfavourable effect of use of drugs with anticholinergic activity on episodic verbal memory. Tests evaluating other cognitive functions were not affected by use of drugs with anticholinergic activity. These associations remained following multivariate analysis adjusting for age, sex, education level, number of anticholinergic drugs, number of co-morbidities, diagnosis, behavioural symptoms and depressive symptoms.
Conclusion
Clinicians should assess the current use of drugs with anticholinergic properties in the elderly, particularly in patients presenting for memory evaluation. In such cases, use of other therapeutic alternatives should be considered.
Similar content being viewed by others
References
WHO. World Health Organization statistical information system [online]. Available from URL: http://www.who.int/whosis/en/index.html [Accessed 2008 Nov]
Ramaroson H, Helmer C, Barberger-Gateau P, et al. Prevalence of dementia and Alzheimer’s disease among subjects aged 75 years or over: updated results of the PAQUID cohort. Rev Neurol (Paris) 2003 Apr; 159(4): 405–11
DeKosky ST. Neurobiology and molecular biology of Alzheimer’s disease. Rev Neurol 2002 Oct 16–31; 35(8): 752–60
Mulsant BH, Pollock BG, Kirshner M, et al. Serum anticholinergic activity in a community-based sample of older adults: relationship with cognitive performance. Arch Gen Psychiatry 2003 Feb; 60(2): 198–203
Rudolph JL, Salow MJ, Angelini MC, et al. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med 2008 Mar 10; 168(5): 508–13
Tune LE. Serum anticholinergic activity levels and delirium in the elderly. Semin Clin Neuropsychiatry 2000 Apr; 5(2): 149–53
Masoudi FA, Baillie CA, Wang Y, et al. The complexity and cost of drug regimens of older patients hospitalized with heart failure in the United States, 1998–2001. Arch Intern Med 2005 Oct 10; 165(18): 2069–76
Lechevallier-Michel N, Molimard M, Dartigues JF, et al. Drugs with anticholinergic properties and cognitive performance in the elderly: results from the PAQUID study. Br J Clin Pharmacol 2005 Feb; 59(2): 143–51
Cao YJ, Mager DE, Simonsick EM, et al. Physical and cognitive performance and burden of anticholinergics, sedatives, and ACE inhibitors in older women. Clin Pharmacol Ther 2008 Mar; 83(3): 422–9
Ancelin ML, Artero S, Portet F, et al. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ 2006 Feb 25; 332(7539): 455–9
Cancelli I, Valentinis L, Merlino G, et al. Drugs with anticholinergic properties as a risk factor for psychosis in patients affected by Alzheimer’s disease. Clin Pharmacol Ther 2008 Jul; 84(1): 63–8
Uusvaara J, Pitkala KH, Tienari PJ, et al. Association between anticholinergic drugs and apolipoprotein E epsilon4 allele and poorer cognitive function in older cardiovascular patients: a cross-sectional study. J Am Geriatr Soc 2009 Mar; 57(3): 427–31
Feinberg M. The problems of anticholinergic adverse effects in older patients. Drugs Aging 1993 Jul–Aug; 3(4): 335–48
Rudd KM, Raehl CL, Bond CA, et al. Methods for assessing drug-related anticholinergic activity. Pharmacotherapy 2005 Nov; 25(11): 1592–601
Mintzer J, Burns A. Anticholinergic side-effects of drugs in elderly people. J R Soc Med 2000 Sep; 93(9): 457–62
Lu CJ, Tune LE. Chronic exposure to anticholinergic medications adversely affects the course of Alzheimer disease. Am J Geriatr Psychiatry 2003 Jul–Aug; 11(4): 458–61
Thienhaus OJ, Allen A, Bennett JA, et al. Anticholinergic serum levels and cognitive performance. Eur Arch Psychiatry Clin Neurosci 1990; 240(1): 28–33
Agence Nationale d’Accréditation et d’Évaluation en Santé (ANAES). Recommandations pratiques pour le diagnostic de la maladie d’alzheimer. Paris: ANAES, 2000 [online]. Available from URL: http://www.unaformec.org/CDRMG/cederom_ol/recos/anaes/alzhe_00.pdf [Accessed 2008 Nov]
Minzenberg MJ, Poole JH, Benton C, et al. Association of anticholinergic load with impairment of complex attention and memory in schizophrenia. Am J Psychiatry 2004 Jan; 161(1): 116–24
Chew ML, Mulsant BH, Pollock BG, et al. Anticholinergic activity of 107 medications commonly used by older adults. J Am Geriatr Soc 2008 May 26; 56(7): 1333–41
Snyder S, Greenberg D, Yamamura HI. Antischizophrenic drugs and brain cholinergic receptors: affinity for muscarinic sites predicts extrapyramidal effects. Arch Gen Psychiatry 1974 Jul; 31(1): 58–61
Richelson E. Pharmacology of antidepressants: characteristics of the ideal drug. Mayo Clin Proc 1994 Nov; 69(11): 1069–81
Folstein MF, Folstein SE, McHugh PR. ‘Mini-mental state’: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975 Nov; 12(3): 189–98
Barbeau E, Didic M, Tramoni E, et al. Evaluation of visual recognition memory in MCI patients. Neurology 2004 Apr 27; 62(8): 1317–22
Deloche GeH D. Test de dénomination orale d’images DO80. Paris: INSERM, 1997
Reitan R. Validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills 1958; 8: 271–6
Cardebat D, Doyon B, Puel M, et al. Formal and semantic lexical evocation in normal subjects: performance and dynamics of production as a function of sex, age and educational level. Acta Neurol Belg 1990; 90(4): 207–17
Grober E, Buschke H, Crystal H, et al. Screening for dementia by memory testing. Neurology 1988 Jun; 38(6): 900–3
Sunderland T, Tariot PN, Cohen RM, et al. Anticholinergic sensitivity in patients with dementia of the Alzheimer type and age-matched controls: a dose-response study. Arch Gen Psychiatry 1987 May; 44(5): 418–26
Han L, Agostini JV, Allore HG. Cumulative anticholinergic exposure is associated with poor memory and executive function in older men. J Am Geriatr Soc 2008 Dec; 56(12): 2203–10
Carriere I, Fourrier-Reglat A, Dartigues JF, et al. Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study. Arch Intern Med 2009 Jul 27; 169(14): 1317–24
Acknowledgements
No sources of funding were used to conduct this study or prepare this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this study. The authors would like to thank Dr Joan Glenn for revising the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Fortin, MP., Rouch, I., Dauphinot, V. et al. Effects of Anticholinergic Drugs on Verbal Episodic Memory Function in the Elderly. Drugs Aging 28, 195–204 (2011). https://doi.org/10.2165/11586580-000000000-00000
Published:
Issue Date:
DOI: https://doi.org/10.2165/11586580-000000000-00000