BackgroundThe use of cholinesterase inhibitors (CHEIs) is commonly associated with urinary incontinence in patients with Alzheimer's disease (AD). This study evaluated the risk of antimuscarinic initiation drugs with the use of CHEIs in AD patients. MethodsThe study used a nested case-control study design involving 2013–2015 Medicare data of AD patients 65 years and older without antimuscarinic use in 2013. Cases were defined as those who initiated antimuscarinic treatment in 2014–2015. Controls with no antimuscarinic use were selected through incidence density sampling and matched to cases on age using a variable-ratio method. The CHEI utilization pattern was classified as current (event-30 days), recent (event-31 to event-90 days), and past (event-91 to event-180 days). Conditional logistic regression was used to assess the association between CHEI use and the risk of antimuscarinic initiation. ResultsThis study included 1,909 cases and 9,064 controls. The adjusted model found that overall CHEI (Adjusted Odds Ratio [aOR] = 1.90, 95 % Confidence Interval [CI]: 1.58–2.28) and current CHEI use (aOR = 1.62, 95 % CI: 1.18–2.21) were associated with an increase in the risk of antimuscarinic initiation compared to non-CHEI use. In addition, the current use of donepezil and rivastigmine significantly increased the risk of antimuscarinic initiation by 48 % (95 % CI: 1.03–2.12) and 171 % (95 % CI: 1.46–5.03), respectively. ConclusionThe study found an increased risk of antimuscarinic initiation with the current use of CHEIs, particularly with donepezil and rivastigmine. These findings underscore the need for careful medication management to minimize prescribing cascades and associated consequences in AD.