Anticholinergic and benzodiazepine medication use and risk of incident dementia: a UK cohort study

Carlota M Grossi,Louise Robinson,Chris Fox,Yoon K Loke,Nicholas Steel,Carol Brayne,Phyo Kyaw Myint,George M Savva,Kathryn Richardson,Noll Campbell,Antony Arthur,Fiona E Matthews,Ian Maidment,Malaz Boustani

doi:10.1186/s12877-019-1280-2

Abstract

BackgroundStudies suggest that anticholinergic medication or benzodiazepine use could increase dementia risk. We tested this hypothesis using data from a UK cohort study.MethodsWe used data from the baseline (Y0), 2-year (Y2) and 10-year (Y10) waves of the Medical Research Council Cognitive Function and Ageing Study. Participants without dementia at Y2 were included (n = 8216). Use of benzodiazepines (including nonbenzodiazepine Z-drugs), anticholinergics with score 3 (ACB3) and anticholinergics with score 1 or 2 (ACB12) according to the Anticholinergic Cognitive Burden scale were coded as ever use (use at Y0 or Y2), recurrent use (Y0 and Y2), new use (Y2, but not Y0) or discontinued use (Y0, but not Y2). The outcome was incident dementia by Y10. Incidence rate ratios (IRR) were estimated using Poisson regression adjusted for potential confounders. Pre-planned subgroup analyses were conducted by age, sex and Y2 Mini-Mental State Examination (MMSE) score.ResultsDementia incidence was 9.3% (N = 220 cases) between Y2 and Y10. The adjusted IRRs (95%CI) of developing dementia were 1.06 (0.72, 1.60), 1.28 (0.82, 2.00) and 0.89 (0.68, 1.17) for benzodiazepines, ACB3 and ACB12 ever-users compared with non-users. For recurrent users the respective IRRs were 1.30 (0.79, 2.14), 1.68 (1.00, 2.82) and 0.95 (0.71, 1.28). ACB3 ever-use was associated with dementia among those with Y2 MMSE> 25 (IRR = 2.28 [1.32–3.92]), but not if Y2 MMSE≤25 (IRR = 0.94 [0.51–1.73]).ConclusionsNeither benzodiazepines nor ACB12 medications were associated with dementia. Recurrent use of ACB3 anticholinergics was associated with dementia, particularly in those with good baseline cognitive function. The long-term prescribing of anticholinergics should be avoided in older people.

Highlights

Studies suggest that anticholinergic medication or benzodiazepine use could increase dementia risk
At Y10, we excluded a further 5 participants classified as having dementia at Y0 but not Y10 and 45 with unknown dementia status at Y10, leaving 220 people with incident dementia and 2825 people without incident dementia included in the study
We did find a statistically significant increase in dementia risk among recurrent users of Anticholinergics with score 3 (ACB3) anticholinergics and an association between ACB3 anticholinergics use and dementia risk among the subgroup with good baseline cognitive function, suggesting that effects might more apparent in different subgroups of the older population

Summary

Introduction

Studies suggest that anticholinergic medication or benzodiazepine use could increase dementia risk. We tested this hypothesis using data from a UK cohort study. Dementia prevention is a public health priority. No disease modifying treatment for dementia exists, but dementia risk and progression can be modified by changing exposure to risk factors affecting any aspect of long-term brain health [1]. Identifying such risk factors is important for dementia prevention and cognitive health. Long-term use of several classes of medications have been suggested to increase future dementia risk. Anticholinergics can adversely affect cognition [2]; guidelines suggest they

Methods

Results

Discussion

Conclusion