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Cognitive decline associated with anticholinergics, benzodiazepines and Z-drugs: Findings from The Irish Longitudinal Study on Ageing (TILDA)

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posted on 23.08.2021, 12:39 by Frank MoriartyFrank Moriarty, George M Savva, Carlota M Grossi, Kathleen BennettKathleen Bennett, Chris Fox, Ian Maidment, Yoon K. Loke, Nicholas Steel, Rose Anne Kenny, Kathryn Richardson
Aim To estimate the association between patterns of anticholinergic, benzodiazepine, and Z-drug medication use and change in cognitive function in middle-aged and older adults.
Method This prospective cohort study used data from the first three waves of The Irish Longitudinal Study on Ageing (TILDA), including community-dwelling adults aged ≥50 years followed for up to four years (n=7,027). Cognitive function was assessed using the Mini Mental State Examination, animal naming test, and word recall tests. Regular medication use was self-reported at baseline and follow-up interviews at two and four years. Pharmacy dispensing claims for a subset (n=2,905) allowed assessment of medication use between interviews and cumulative dosage. Medication use at consecutive waves of TILDA was analysed in relation to change in cognitive function between waves.
Results Strongly anticholinergic medications (Anticholinergic Cognitive Burden scale 3), benzodiazepines, and Z-drugs were reported by 7.3%, 5.8% and 5.1% of participants respectively at any time during the study. Adjusting for potential confounders, new anticholinergic use between interviews was associated with change in recall score (−1.09, 95% confidence interval −1.64, −0.53) over 2 years compared to non-use, but not with MMSE (0.07; 95%CI -0.21, 0.34) or animal naming (−0.70; −1.43, 0.03). The pharmacy claims analysis was consistent with this finding. Other hypothesised associations were not supported.
Discussion Except for new use of anticholinergic medications, no other findings supported a risk of cognitive decline over 2-year periods in this middle-aged and older cohort. Patients and prescribers should weigh this potential risk against potential benefits of commencing anticholinergic medications. What is already known about this subject: Benzodiazepines, Z-drugs and drugs with anticholinergic activity have been linked with cognitive impairment. Most evidence is derived from observational studies of older people, with little research on middle-aged adults. Medication effects may be confounded by indication and these medications are often prescribed for early symptoms of prodromal stages of dementia. What this study adds: In this study of adults aged 50 years and older, no consistent pattern of change in cognitive function was associated with the medication exposures tested, except for reduced recall among new users of anticholinergic medications. Further research in the younger-old adult population should be conducted to confirm these findings.

Funding

UK Alzheimer’s Society [AS- PG -2013 -017]

Funding for TILDA is provided by the Irish Government, the Atlantic Philanthropies and Irish Life

History

Comments

This is the peer reviewed version of the following article: Moriarty F, et al. Cognitive decline associated with anticholinergics, benzodiazepines and Z-drugs: Findings from The Irish Longitudinal Study on Ageing (TILDA). Br J Clin Pharmacol. 2021;87(7):2818-2829., which has been published in final form at https://doi.org/10.1111/bcp.14687. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. Pre-print is available on medRxiv, https://doi.org/10.1101/2020.05.09.20095661 & RCSI repository https://hdl.handle.net/10779/rcsi.14939073.v1

Published Citation

Moriarty F, et al. Cognitive decline associated with anticholinergics, benzodiazepines and Z-drugs: Findings from The Irish Longitudinal Study on Ageing (TILDA). Br J Clin Pharmacol. 2021;87(7):2818-2829.

Publication Date

3 December 2020

PubMed ID

33270264

Department/Unit

  • HRB Centre for Primary Care Research
  • General Practice
  • Data Science Centre

Research Area

  • Population Health and Health Services

Publisher

Wiley

Version

  • Accepted Version (Postprint)