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

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.