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

Frank Moriarty, George Savva, Carlota M. Grossi, Kathleen Bennett, Chris Fox, Ian Maidment, Yoon K. Loke, Nicholas Steel, Rose Anne Kenny, Kathryn Richardson

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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.

Original languageEnglish
Pages (from-to)2818-2829
Number of pages12
JournalBritish Journal of Pharmacology
Issue number7
Early online date3 Dec 2020
Publication statusPublished - Jul 2021


  • Z-drugs
  • anticholinergic medication
  • benzodiazepines
  • cognitive function
  • pharmacoepidemiology

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