Probing polypharmacy, ageing and sex effects on physical function using different tests

Background: Ageing, sex and polypharmacy affect physical function.Objectives: This mouse study investigates how ageing, sex and polypharmacy interact and affect grip strength, balance beam and wire hang, correlating and comparing the different test results between and within subgroups.Methods: Young (2.5 months) and old (21.5 months) C57BL/6 J male and female mice (n = 10-6/group) were assessed for physical function at baseline on grip strength, balance beam and wire hang with three trials of 60 s (WH60s) and one trial of 300 s (WH300s). Mice were randomised to control or diet containing a high Drug Burden Index (DBI, total anticholinergic and sedative drug exposure) polypharmacy regimen (metoprolol, simvastatin, citalopram, oxycodone and oxybutynin at therapeutic oral doses). Following 6-8 weeks of treatment, mice were reassessed.Results: High DBI polypharmacy and control mice both showed age group differences on all tests (p < 0.05). Only control mice showed sex differences, with females outperforming males on the WH60s and balance beam for old mice, WH300s for young mice (p < 0.05). Polypharmacy reduced grip strength in all subgroups (p < 0.05) and only in old females reduced wire hang time and cumulative behaviour and balance beam time and %walked (p < 0.05). Physical function assessments were all correlated with each other, with differences between subgroups (p < 0.05), and mice within subgroups showed interindividual variability in performance.Conclusion: Age, sex and polypharmacy have variable effects on different tests, and behavioural measures are useful adjuvants to assessing performance. There was considerable within-group variability in change in measures over time. These findings can inform design and sample size of future studies.