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

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.

Anticholinergic Drug Burden and Risk of Incident MCI and Dementia

“…This Scottish study did not identify individuals with MCI but rather diagnosed dementia using International Classification of Diseases-10 criteria and neuropsychological test scores corrected for age and childhood IQ. Among 7027 participants in The Irish Longitudinal Study on Ageing15 aged 50 years and older and followed for 2 years, new use of anticholinergics, and to some extent, recurrent anticholinergic drug use, was associated with statistically significant reductions in recall scores, but no evidence of decline on MMSE or verbal fluency. In the community-based Australian PATH Through Life cohort,14 among 2058 randomly selected persons 60 to 64, interviewed twice over 4 years, exposure to anticholinergic medications was associated with lower level of complex attention in the young old, but not with greater cognitive decline over time.…”

“…For example, in most memory clinics, the majority of individuals with MCI go on to develop dementia, because they have underlying brain diseases that result in dementia; whereas, in the population setting, most individuals with MCI remain mildly impaired because their impairment is due to a variety of underlying conditions, not all neurodegenerative or cerebrovascular in etiology 11,12. Among the 25 studies that met Cochrane inclusion criteria, 5 were randomly sampled from the population (“population based”) 13–17…”

SART and Individual Trial Mistake Thresholds: Predictive Model for Mobility Decline

“…Global cognitive function was assessed using the Mini-Mental State Examination (MMSE) test, giving participants a score from 0 (minimum) to 30 (maximum) [ 27 , 37 , 38 ]. We considered the MMSE score in wave 1 ( ) and wave 3 ( and, in line with previous recommendations [ 39 ], defined as clinically meaningful cognitive decline a decrease of at least 2 points between wave 1 and 3 ( ).…”

The Syncope-Falls Index: a tool for predicting risk of syncope and complex falls in the older adult based on cumulative health deficits

“…As regards medications, the list of anticholinergics, benzodiazepines and Z-drugs characterised in TILDA has been described elsewhere. (24) For the cognitive deficit, we selected an MMSE score of less than 24 points. (25) Each deficit was coded 1 if it was present or 0 if it was not.…”