The effect of polypharmacy on prefrontal cortex activation during single and dual task walking in community dwelling...

Polypharmacy, defined as the use of 5 or more medications is associated with multiple adverse outcomes in older adults, including falls and slow gait velocity. However, the relationship between polypharmacy and cortical control of locomotion has not been reported. The purpose of this study was to examine the relationship between polypharmacy and activation patterns in the prefrontal cortex (PFC), a brain region involved in higher order control of locomotion during attention-demanding conditions.

Using Functional Near Infrared Spectroscopy (fNIRS) to quantify PFC oxygenated hemoglobin (HbO₂) levels, we performed a cross sectional analysis of 325 community dwelling adults age ≥65 years, and examined HbO₂ levels during single tasks (Single-Task-Walk (STW), (talking, cognitive interference (Alpha)) and Dual-Task Walk (DTW)).

The prevalence of polypharmacy was 33% (n = 104) amongst the 325 participants (mean age 76.4 ± 6.7 years, 56% women). Among the 221 participants with no polypharmacy there was an increase in HbO₂ levels from STW to DTW (estimate = -0.625; p = <0.001) and from Alpha to DTW (estimate=-0.079; p = 0.031). Polypharmacy status, however, moderated the change in HbO₂ levels comparing the two single tasks to the dual-task walking condition. Specifically, the presence of polypharmacy was associated with an attenuated increase in HbO₂ levels from STW to DTW (estimate = 0.149; p = 0.027) and with a decline in HbO₂ levels from Alpha to DTW (estimate = 0.169; p = 0.009) after adjustments for potential confounders including medical comorbidities and the use of high-risk medications.

The results of this study further support the need for clinicians to reduce polypharmacy in older adults, given its significant association with the PFC hemodynamic response during attention-demanding locomotion.