Using computational video analysis in ageing mice to evaluate the effects of chronic monotherapy, polypharmacy and deprescribing over time

Background In clinical studies of older adults, polypharmacy (use of ≥ 5 drugs) and the Drug Burden Index (DBI; measures exposure to anticholinergic and sedative drugs) are associated with impaired physical function and frailty. We used computational video analysis of aging mice to examine the impact of medications on morphometric and gait function. Methods Middle-aged (12 month) male mice were administered therapeutic doses of medications in polypharmacy regimens with different DBI scores or monotherapy with medications from the High DBI polypharmacy regimen. At age 21 months, half of the treated animals had their medications deprescribed (discontinued). Open field videos and mouse clinical frailty index were recorded at 12, 15, 18, 21 and 24 months. After applying open-source neural networks to the videos, the gained features were analysed to detect differences between the treatment groups and control over time using a state-space model with change point detection. Results We measured 49 morphometric and gait features for 278 mice. The sum of effects of constituent monotherapies did not equal the effects of polypharmacy. Consistent with clinical data, greater gait and posture changes were observed with polypharmacy regimens with increasing DBI scores. Deprescribing effects varied between medications, consisting of reversible, irreversible and novel changes. Different medication exposures had different effects on gait, posture and the prediction of frailty. Conclusion Computational video analysis of preclinical data is a promising tool for high-throughput, sensitive detection of medication effects in aging.