Relationship between cognitive function and brain activation in late-life depression patients with and without frailty: a functional near-infrared spectroscopy study.

BACKGROUND AND OBJECTIVE: Frailty and cognitive impairment commonly co-occur in late-life depression (LLD), but the task-evoked cortical alterations associated with frailty-related cognitive dysfunction in LLD remain unclear. We examined cognitive performance and cortical activation during a verbal fluency task (VFT) in LLD patients with and without frailty. METHODS: Ninety-two older adults were included: 30 frail LLD patients (F-LLD), 32 non-frail LLD patients (NF-LLD), and 30 healthy controls (HC). Frailty was assessed using the Fried frailty phenotype. Global cognition and verbal fluency were assessed using the Montreal Cognitive Assessment (MoCA) and correct words generated during the VFT, respectively. Functional near-infrared spectroscopy quantified integrated oxygenated hemoglobin (HbO2) responses during the VFT. RESULTS: F-LLD patients had lower MoCA scores and poorer VFT performance than NF-LLD patients and HC (both p < 0.001). After false discovery rate (FDR) correction, group differences remained significant in DLPFC_L (FDR-adjusted p < 0.001), TC_L (FDR-adjusted p < 0.001), and Broca_L (FDR-adjusted p = 0.005). DLPFC_L activation decreased stepwise (HC > NF-LLD > F-LLD). In LLD patients, higher Fried frailty scores were independently associated with lower activation in all three regions after covariate adjustment (all p < 0.05), whereas greater DLPFC_L activation was independently associated with better MoCA and VFT performance (both p < 0.001). CONCLUSIONS: Frailty in LLD was associated with greater cognitive impairment and reduced left frontotemporal activation, particularly DLPFC_L hypoactivation, a potential neural correlate of frailty-related cognitive dysfunction.