Subregion-Specific Prefrontal Activation Predicts Fall Risk and Fall Timing in Older Adults with Mild Cognitive Impairment.

Abstract

To investigate whether time-varying prefrontal cortex (PFC) activation during dual-task walking is associated with fall risk and time to first fall in older adults with mild cognitive impairment (MCI). Prospective longitudinal cohort study. Community-based assessment with 12-month follow-up. One hundred ten community-dwelling older adults with MCI (N=110). Not applicable. Oxygenated hemoglobin changes in PFC subregions during dual-task walking were measured using functional near-infrared spectroscopy. Baseline global cognition and functional mobility were assessed. The primary outcomes were fall occurrence and time to first fall during 12 months of prospective follow-up. Associations with fall risk and time to first fall were examined using multivariable logistic regression, Cox proportional hazards models with time-varying coefficients, and Kaplan-Meier analyses, adjusting for age, sex, and global cognition. During follow-up, 39 participants (35.5%) experienced at least one fall. Greater early-phase DLPFC activation during dual-task walking was independently associated with higher odds of falling (odds ratio, 2.36; 95% CI, 1.02-5.59; p=0.048) and shorter time to first fall (hazard ratio, 3.00; 95% CI, 1.49-6.04; p=0.002). This association attenuated significantly over time, supported by a significant DLPFC-by-time interaction (hazard ratio, 0.24; 95% CI, 0.15-0.40; p<0.001). Slower Timed Up and Go performance was also independently associated with higher fall risk and shorter time to first fall. Exaggerated early-phase DLPFC activation during cognitively demanding walking represents a time-sensitive neural prognostic marker of fall vulnerability in older adults with MCI. Integrating cortical activation measures with functional mobility assessment may enhance fall risk stratification in clinical and community settings.