Anticholinergic and Benzodiazepine Use and Dementia Risk

Study Overview

  • Research on anticholinergic and benzodiazepine medication use and dementia risk.
  • UK cohort study using data from the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS).
  • Participants without dementia at Y2 were included (n = 8216).
  • Incident dementia was measured by Y10.

Methods

  • Use of benzodiazepines and anticholinergics (ACB3 and ACB12) were coded as:
    • Ever use (use at Y0 or Y2)
    • Recurrent use (Y0 and Y2)
    • New use (Y2, but not Y0)
    • Discontinued use (Y0, but not Y2)
  • Incidence rate ratios (IRR) estimated using Poisson regression adjusted for confounders.
  • Subgroup analyses by age, sex, and Y2 Mini-Mental State Examination (MMSE) score.

Results

  • Dementia incidence was 9.3% (N = 220 cases) between Y2 and Y10.
  • Adjusted IRRs for developing dementia:
    • Benzodiazepines ever-users: 1.06 (0.72, 1.60)
    • ACB3 ever-users: 1.28 (0.82, 2.00)
    • ACB12 ever-users: 0.89 (0.68, 1.17)
  • For recurrent users, the respective IRRs were:
    • Benzodiazepines: 1.30 (0.79, 2.14)
    • ACB3: 1.68 (1.00, 2.82)
    • ACB12: 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]).

Conclusions

  • Neither 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.
  • Long-term prescribing of anticholinergics should be avoided in older people.

Statistical Analyses

  • Separate univariable Poisson regression models were used to estimate incidence rate ratios (IRR).
  • Multivariable analysis included demographic, health, and cognition related variables.
  • Pre-planned stratified analyses were conducted by year of birth, sex, and MMSE score at Y2.
  • Inverse probability weights were used to adjust for non-response at Y10.

Sensitivity Analyses

  • Excluding potential mediating or colliding variables.
  • Using multiple imputation to identify screen-only participants with dementia at baseline.
  • Taking into account the possibility that higher mortality rates might suppress estimates of dementia incidence.

Medication Use

  • Among those surviving to 10 years, 7.5% reported ever use of a BZD.
  • Use of ACB3 at baseline or 2-year follow-up was reported by 5.6% of the surviving sample; 2.3% were recurrent users.
  • 53% of the surviving sample reported ACB1 or ACB2 at baseline or 2-year follow-up, with 34% reporting ACB1 or ACB2 use at both waves.

Key Findings

  • No significant association between dementia and ever-use of short or medium-acting, long-acting, hypnotic or anxiolytic BZDs, or for anti-depressant or ‘other’ anticholinergics.
  • The effect of ACB3 was restricted to those with good baseline cognitive function (MMSE > 25).