Frailty, polypharmacy, deprescribing and 23-hour activity: insights from a mouse model

Area of Science:

• Gerontology
• Pharmacology
• Neuroscience

Background:

• Older adults with frailty often face polypharmacy and deprescribing challenges.
• The interplay between frailty, medication effects, and functional outcomes remains unclear.

Purpose of the Study:

• To investigate the effects of chronic drug regimens (monotherapy, polypharmacy) and deprescribing on activity and frailty in aged mice.
• To explore the relationship between medication-induced changes, frailty trajectories, and behavioral outcomes.

Main Methods:

• Aged male C57BL/6J mice received control, monotherapy, or polypharmacy diets.
• Deprescribing was initiated at 21 months, with behavioral assessments at 24 months using the LABORAS system.
• Drug Burden Index (DBI) quantified exposure to sedative and anticholinergic medications.

Main Results:

• Polypharmacy, especially with higher DBI, markedly altered activity, differing from monotherapy effects.
• Deprescribing led to partially reversible and some irreversible changes in behavior.
• Unique correlations between frailty and behavioral outcomes were observed across intervention groups.
• Four distinct clusters emerged, characterized by different frailty trajectories, deficits, and activity patterns.

Conclusions:

• Chronic medication use and deprescribing influence activity levels, frailty, and its progression in preclinical models.
• Understanding the context of polypharmacy and deprescribing is crucial for translating frailty research findings.