Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2014 Feb;62(2):336-41.
doi: 10.1111/jgs.12632. Epub 2014 Jan 13.

Methodological challenges in determining longitudinal associations between anticholinergic drug use and incident cognitive decline

Mandavi Kashyap  1 , Sylvie Belleville, Benoit H Mulsant, Sarah N Hilmer, Amelie Paquette, Le Mai Tu, Cara Tannenbaum
Affiliations
Comparative Study

Methodological challenges in determining longitudinal associations between anticholinergic drug use and incident cognitive decline

Mandavi Kashyap et al. J Am Geriatr Soc. 2014 Feb.

Abstract

Objectives: To compare the effect of using different anticholinergic drug scales and different models of cognitive decline in longitudinal studies.

Design: Longitudinal cohort study.

Setting: Outpatient clinics, Quebec, Canada.

Participants: Individuals aged 60 and older without dementia or depression (n = 102).

Measurements: Using baseline and 1-year follow-up data, four measures of anticholinergic burden (anticholinergic component of the Drug Burden Index (DBI-Ach), Anticholinergic Cognitive Burden (ACB), Anticholinergic Drug Scale (ADS), and Anticholinergic Risk Scale (ARS)) were applied. Three models of cognitive decline (worsening of raw neuropsychological test scores, Reliable Change Index (RCI), and a standardized regression based measure (SRB)) were compared in relation to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria for the onset of a new mild neurocognitive disorder. The consistency of associations was examined using logistic regression.

Results: The frequency of identifying individuals with an increase in anticholinergic burden over 1 year varied from 18% with the DBI-Ach to 23% with the ACB. The frequency of identifying cognitive decline ranged from 8% to 86% using different models. The raw change score had the highest sensitivity (0.91), and the RCI the highest specificity (0.93) against DSM-V criteria. Memory decline using the SRB method was associated with an increase in ACB (odds ratio (OR) = 5.3, 95% confidence interval (CI) = 1.1-25.8), ADS (OR = 5.7, 95% CI = 1.1-27.7), and ARS (OR = 6.5, 95% CI = 1.34-32.3). An increase in the DBI-Ach was associated with a decline on memory testing using the raw change score method (OR = 4.2, 95% CI = 1.8-15.4) and on the Trail-Making Test Part B using SRB (OR = 2.9, 95% CI = 1.1-8.0). No associations were observed using the DSM-V criteria or RCI method.

Conclusion: The choice of different methods for defining drug exposure and cognitive decline will have a significant effect on the results of pharmacoepidemiological studies.

Keywords: anticholinergic drug exposure; cognitive decline; longitudinal study; methods; older adults.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Sensitivity and specificity of different methods of measuring cognitive decline (worsening performance on at least one neuropsychological test) against Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V), diagnosis of mild neurocognitive impairment at 1-year follow-up.
See this image and copyright information in PMC

References

    1. Terry AV, Jr, Buccafusco JJ. The cholinergic hypothesis of age and Alzheimer's disease-related cognitive deficits: Recent challenges and their implications for novel drug development. J Pharmacol Exp Ther. 2003;306:821–827. - PubMed
    1. Paquette A, Gou P, Tannenbaum C. Systematic review and meta-analysis: Do clinical trials testing antimuscarinic agents for overactive bladder adequately measure central nervous system adverse events? J Am Geriatr Soc. 2011;59:1332–1339. - PubMed
    1. Wagg A, Dale M, Tretter R, et al. Randomised, multicentre, placebo-controlled, double-blind crossover study investigating the effect of solifenacin and oxybutynin in elderly people with mild cognitive impairment: The SENIOR Study. Eur Urol. 2013;64:74–81. - PubMed
    1. 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;332:455–458. - PMC - PubMed
    1. 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;169:1317–1324. - PMC - PubMed

Publication types

Substances

LinkOut - more resources