OBJECTIVE:

Antimuscarinic use along with cholinesterase inhibitors (CHEIs) can nullify the modest treatment benefit of CHEIs and can worsen Alzheimer’s disease (AD) due to therapeutically opposing mechanisms of action. This worsening of cognition can precipitate prescribing of memantine for moderate-to-severe AD. Therefore, this study assessed the risk of memantine initiation in older adults with AD using antimuscarinics and CHEIs.

METHODS:

This nested case-control study used Medicare data from 2013-2015 and included patients > 65 years with AD, using CHEI, and not using antimuscarinics and memantine in 2013. Cases were those initiating memantine during 2014-2015, and those without memantine were controls. Controls were assigned a random event date based on the distribution of time-to-event in cases; variable ratio matching on age at the event was used to match cases and controls. The exposure was categorized as use of antimuscarinics only, CHEI only, both, or none during the 3-month lookback before the event. The Andersen Behavioral Model was used to identify covariates during the baseline period. Conditional logistic regression was used to assess the risk of memantine initiation with antimuscarinic and CHEI use.

RESULTS:

The study included 13,673 cases and 64,853 controls; most were 80 years or older (65.7%), female (69.9 %), non-Hispanic White (79.5%), had 1-2 Elixhauser comorbidities (42.6%), and were mildly frail (48.1%). Of these patients, 52.3%(n=41,069) received neither CHEI nor antimuscarinics, 0.5%(n=395) received both, 47.1%(n=36,952) received CHEI only, and 0.1%(n=110) received antimuscarinics only. After adjusting for potential confounders, all exposure groups involving only antimuscarinics (OR=1.9, 95% CI:1.2-3.0;p=0.01), only CHEI (OR=2.5, 95% CI:2.4-2.6;p<0.01), and both CHEI and antimuscarinics (OR=3.0, 95% CI:2.4-3.8;p<0.01) increased the likelihood of receiving memantine compared to those who received neither.

CONCLUSION:

The study found that concomitant use of antimuscarinics and CHEIs was limited in AD, and the risk of memantine initiation was comparable across all exposure groups.