Anticholinergic Medication Use, Dopaminergic Genotype, and Recurrent Falls

Abstract

Background: Anticholinergic medications are associated with fall risk. Higher dopaminergic signaling may provide resilience to these effects. We tested interactions between anticholinergic medication use and dopaminergic genotype on risk for recurrent falls over 10 years.

Methods: Participants in the Health, Aging, and Body Composition (Health ABC) study (n = 2 372, mean age = 73.6; 47.8% men; 60.0% White) without disability or anticholinergic use at baseline were followed for up to 10 years for falls. Medication use was documented in 7 of 10 years. Highly anticholinergic medications were defined by Beers criteria, 2019. Recurrent falls were defined as ≥2 in the 12 months following medication assessment. Generalized estimating equations tested the association of anticholinergic use with recurrent falls in the following 12 months, adjusted for demographics, health characteristics, and anticholinergic use indicators. Effect modification by dopaminergic genotype (catechol-O-methyltransferase [COMT]; Met/Met, higher dopamine signaling, n = 454 vs Val carriers, lower dopamine signaling, n = 1 918) was tested and analyses repeated stratified by genotype.

Results: During follow-up, 841 people reported recurrent falls. Anticholinergic use doubled the odds of recurrent falls (adjusted odds ratio [OR] [95% CI] = 2.09 [1.45, 3.03]), with suggested effect modification by COMT (p = .1). The association was present in Val carriers (adjusted OR [95% CI] = 2.16 [1.44, 3.23]), but not in Met/Met genotype (adjusted OR [95% CI] = 1.70 [0.66, 4.41]). Effect sizes were stronger when excluding baseline recurrent fallers.

Conclusion: Higher dopaminergic signaling may provide protection against increased 12-month fall risk from anticholinergic use. Assessing vulnerability to the adverse effects of anticholinergic medications could help in determination of risk/benefit ratio for prescribing and deprescribing anticholinergics in older adults.

Keywords: Anticholinergic medications; Dopamine; Epidemiology; Falls.