Sticking With It: A Meta-Review of Anti-Dementia Medication Use and Adherence

Patients with dementia progressively lose cognitive function, eventually leading to the inability to perform daily activities. Dementia affects millions of people worldwide and is more common in older adults but is not a normal part of aging. Clinicians prescribe anti-dementia drugs (ADDs) to slow the progression of cognitive decline, but these medications are not curative.¹

Patients with dementia progressively lose cognitive function | Image credit: pikselstock | stock.adobe.com

ADDs include cholinesterase inhibitors (ChEIs)—such as donepezil (Aricept; Eisai Inc), rivastigmine (Exelon; Novartis), and galantamine (Razadyne; Johnson & Johnson)—and the N-methyl-D-aspartate receptor antagonist memantine (Namenda; AbbVie).² Suboptimal persistence with ADDs is associated with poorer clinical outcomes, including accelerated disease progression, cognitive decline, and increased health care system dependence.²

In study results published in Age and Ageing, researchers conducted a systematic review and meta-analysis of persistence rates with ADDs. Their goal was to identify factors influencing persistence and to supply accurate current data to clinicians to inform decisions about the need for dose changes or interventions to address adherence behaviors. The primary objective of the analysis was to assess 12-month persistence with ChEIs and memantine among patients with dementia in real-world practice, as reported in observational studies. The authors included 68 prospective and retrospective studies in their review and used a subset (n=22) for the meta-analysis.²

The analysis of data from nearly 700,000 patients showed that only about half of them remained persistent at 12 months, with persistence definition (particularly regarding the permissible gap between prescription refills) influencing heterogeneity across studies.²

The study findings demonstrated varying persistence rates across different follow-up periods, with higher rates at 4 to 7 months (65%) compared with 24 months (21%) and 36 months (31%). The authors speculate that the early discontinuation of ADDs may be due to a perceived lack of benefit, whereas later discontinuation may be influenced by limited ongoing efficacy and adverse effects.²

The analysis showed a higher mean persistence rate for memantine (61%) compared with ChEIs (46%), but the difference was not statistically significant. The authors speculate that this observation may stem from a more favorable safety profile for memantine.²

The authors compiled a list of factors that may influence persistence, including severity of dementia, educational level, medication burden, economic standing, treatment provider type and practices, need for long-term care, and adverse drug reactions.²

The researchers acknowledge several limitations to their analysis²:

• They used only English-language publications, potentially leading to publication bias.
• Discrepancies in the definitions of persistence and variability between studies hindered direct comparisons between all reviewed studies.
• Pertinent data (patient mortality, attrition rates, therapeutic modifications, planned discontinuation due to disease progression) and patient demographic data (type of dementia, time since diagnosis, comorbid conditions) were inconsistently documented.

The meta-analysis demonstrated relatively low persistence to ADDs, which varied according to the evaluation criteria used. The authors recommend standardizing data collection methods and reporting to facilitate future analyses and development of interventions to improve persistence for ADDs to improve patient outcomes.²

Reference

1. About Dementia. CDC. Updated August 17, 2024. Accessed June 25, 2025. https://www.cdc.gov/alzheimers-dementia/about/index.html

2. 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