OBJECTIVES: Limited comparative data exists regarding prescribing cascade of antimuscarinics across individual Acetylcholinesterase inhibitors (AChEIs) in dementia. This study examined the risk of antimuscarinics cascade across individual AChEIs in older adults with dementia.

METHODS: The study involved new-user retrospective cohort design using multi-year January 2005-December 2018 TriNetX, electronic medical record data from federated global electronic network. The base cohort included patients aged 65 years or more with diagnosis of dementia using AChEIs (donepezil, galantamine, or rivastigmine). The study identified new-users of individual AChEIs with index dates from Jan 1, 2006, to Jun 31, 2018, and followed them for up to 180 days for antimuscarinics initiation. Patients with any antimuscarinic use, Overactive bladder (OAB) diagnosis one-year before individual AChEIs index date were excluded. Cox proportional hazard model was used to assess the association between individual incident AChEI and antimuscarinics prescribing cascade after controlling for several covariates.

RESULTS: The study identified 47,059 older adults with dementia who were incident users of AChEIs. Most were females (62.63%), White (81.24), and in age group of 75-84 years (61.27%). Most of these were on donepezil users 39,100 (83.09%), followed by rivastigmine 5,805 (12.34%) and galantamine 2,154 (4.58%). Overall, 8.16% of study cohort had incident OAB diagnosis or antimuscarinic prescription. Antimuscarinic initiation was 3.67% within six months of AChEIs prescription, and cascade varied widely across individual agents - donepezil (3.86%), rivastigmine (2.56%), and galantamine (2.92%). The mean time to antimuscarinics initiation was 29.87 (±49.29) days for donepezil, 38.14 (±53.53) days for rivastigmine, and 30.50 (±51.65) days for galantamine. Cox proportional hazard analyses revealed that donepezil users had an increased risk of receiving antimuscarinics (aHR=1.55; 95% CI, 1.31- 1.83), compared to rivastigmine. CONCLUSIONS: The study found that donepezil is more likely to lead to antimuscarinics cascade compared to rivastigmine. Future studies are needed to evaluate potential consequences of this cascade in dementia.