Only Half of Patients Adherent to Antidementia Medication Regimens at 1 Year: New Meta-Analysis Results

Only half of adults prescribed antidementia drugs (ADD) remain on therapy after 1 year, according to a large-scale meta-analysis that pooled data from 68 real-world studies involving nearly 700,000 adults aged 50 years or older. The average 12-month persistence rate was 49% (95% CI, 42%–56%), exposing a significant gap in long-term adherence to inhibitors (ChEis) and memantine.¹

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Researchers found that rates varied widely based on how studies defined persistence, particularly whether a permissible gap between prescription refills was used. They also found that adherence waned over time.¹

The research and the findings reflect an issue that will become only more pronounced as greater proportions of the population become vulnerable to cognitive decline and also as the diagnostic methods become more sophisticated, identifying greater numbers.² The investigators emphasized that improving medication persistence could support better symptom control, slow disease progression, and reduce health system burden.

The study, published in Age and Ageing, was conducted to address inconsistencies in how persistence to ADDs has been evaluated in the literature. Despite the availability of newer amyloid-targeting therapies, ChEis (donepezil, rivastigmine, galantamine) and the NMDA receptor antagonist memantine remain central to symptomatic management of dementia in most clinical settings. However, previously published persistence estimates have ranged widely, from 20% to 66% according to data cited in the study, with differences driven in part by the inconsistencies in definitions, follow-up durations, and data sources, according to the authors.

The study’s primary goal was to identify factors influencing medication persistence and to provide clinicians who care for older adults experiencing cognitive decline with current data that will better inform clinical practice. For the systematic review and meta-analysis, investigators drew studies from 4 key databases from 1995 through early 2024. Only studies that assessed medication persistence outside of clinical trial settings and with clearly defined 12-month persistence outcomes were included. Persistence was defined as continued use of an ADD at 12 months, with some studies using prescription refill gaps to operationalize discontinuation. The final dataset included diverse populations across Europe, Asia, and North America.

FINDINGS

As noted, the mean persistence rate across the final 68 studies included (n = 684,493 ) was 49%. In a subgroup analysis of studies where a permissible gap for medication refills was not required, the persistence estimate rose to 67% (95% CI: 38%–90%). Analysis of studies of memantine alone found higher pooled 12-month persistence of 61% than for ChEis alone (46%). While the difference was not statistically significant, the authors noted the disparity was likely the result of differences in tolerability between the ADDs.

Persistence rates also varied across follow-up periods, according to the study, with higher rates at 4 to 7 months (65%) compared with 24 months (21%) and 36 months (31%). The authors speculated that the early discontinuation of ADDs may be the result of a perceived lack of benefit, whereas later discontinuation may be influenced by limited or uncertain ongoing efficacy and adverse effects.²

Use of a permissible refill gap in the definition of persistence was found to be an independent predictor of heterogeneity between studies.

Among the study’s limitations the authors point to the variable definitions of persistence, which hindered the ability to compare all studies comprehensively. Also inconsistent across studies was detailed reporting of clinical and demographic information, which the authors said limited the ability to assess potential confounding effects on persistence.

The authors conclude by noting that the poor findings from their study support further research to identify targeted interventions that promote continued use of ADDs. Among their suggestions are enhanced education efforts targeting both patients and clinicians that address adverse effect concerns and “collaborative care models that integrate pharmacists and other healthcare professionals to provide ongoing support and medication management.

“Future research should focus on rigorously evaluating the effectiveness and cost-effectiveness of these interventions in diverse real-world settings.”

References

1. Sistanizad M, Peterson GM, Ling T, Salahudeen MS, Akondi VM, Bezabhe WM. Persistence with anti-dementia medications: a systematic review and meta-analysis. Age Ageing. 2025;54(6):afaf151. doi:10.1093/ageing/afaf151
2. About Dementia. CDC. Updated August 17, 2024. Accessed June 25, 2025. https://www.cdc.gov/alzheimers-dementia/about/index.html