Persistence with anti-dementia medications: a systematic review and meta-analysis

Abstract

Background: Suboptimal persistence with anti-dementia drugs (ADDs) in patients with dementia is associated with poorer clinical outcomes, including accelerated disease progression, cognitive decline and increased healthcare utilisation. This study aimed to systematically review real-world persistence rates with ADDs and identify factors influencing persistence.

Methods: We followed the Cochrane methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched Medline, Embase, PsycINFO and CINAHL from 1 January 1995 to 5 February 2024. Pooled persistence rates were calculated using random-effects Mantel-Haenszel models. Heterogeneity was assessed using I2 statistics, publication bias via funnel plots and Egger's/Begg's tests, and moderators were explored through meta-regression.

Results: We included 68 studies involving 684,493 participants aged 50 years and older who received ADD. The mean 12-month persistence rate was 49% (95% CI: 42%-56%). Subgroup analyses revealed higher persistence for studies where a permissible gap for medicine refills was not required based on the methodology (67%, 95% CI: 38%-90%), those examining memantine (61%, 95% CI: 38%-82%), studies published between 2011 and 2015 (54%, 95% CI: 41%-68%) and studies conducted in Europe (57%, 95% CI: 43%-71%). Of these, the permissible gap remained an independent predictor of between-study heterogeneity in persistence (β = 0.36, 95% CI: 0.18-0.54).

Conclusion: The meta-analysis demonstrated relatively low persistence to ADDs, which varied according to the evaluation criteria used. Targeted interventions to improve persistence with therapy may lead to better outcomes in patients with dementia. Also, a standardised framework for measuring persistence could improve research reliability.

Keywords: anti-dementia drugs; dementia; medication persistence; older people; systematic review.

Figure 1

PRISMA flow diagram of the study selection process.

Figure 2

Forest plot: pooled proportion of 12-month persistence with ChEIs and memantine at 12 months; ChEI: cholinesterase inhibitor, NR: not required.