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

Br J Clin Pharmacol. 2021 Jul;87(7):2818-2829. doi: 10.1111/bcp.14687. Epub 2020 Dec 18.

Abstract

Aims: 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.

Methods: 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 4 years (n = 7027). 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 2 and 4 years. Pharmacy dispensing claims for a subset (n = 2905) 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; 95% CI -1.43, 0.03). The pharmacy claims analysis was consistent with this finding. Other hypothesised associations were not supported.

Conclusions: 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.

Keywords: Z-drugs; anticholinergic medication; benzodiazepines; cognitive function; pharmacoepidemiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging
  • Benzodiazepines / adverse effects
  • Cholinergic Antagonists / adverse effects
  • Cognitive Dysfunction* / chemically induced
  • Cognitive Dysfunction* / epidemiology
  • Humans
  • Longitudinal Studies
  • Middle Aged
  • Pharmaceutical Preparations*
  • Prospective Studies

Substances

  • Cholinergic Antagonists
  • Pharmaceutical Preparations
  • Benzodiazepines