Mediation Analyses of the Role of Apathy on Motoric Cognitive Outcomes.

Recent literature indicates that apathy is associated with poor cognitive and functional outcomes in older adults, including motoric cognitive risk syndrome (MCR), a predementia syndrome. However, the underlying biological pathway is unknown. The objectives of this study were to (1) examine the cross-sectional associations between inflammatory cytokines (Interleukin 6 (IL-6) and C-Reactive Protein (CRP)) and apathy and (2) explore the direct and indirect relationships of apathy and motoric cognitive outcomes as it relates to important cognitive risk factors. N = 347 older adults (≥65 years old) enrolled in the Central Control of Mobility in Aging Study (CCMA). Linear and logic regression models showed that IL-6, but not CRP was significantly associated with apathy adjusted for age, gender, and years of education (β = 0.037, 95% CI: 0.002-0.072, p = 0.04). Apathy was associated with a slower gait velocity (β = -14.45, 95% CI: -24.89-4.01, p = 0.01). Mediation analyses demonstrated that IL-6 modestly mediates the relationship between apathy and gait velocity, while apathy mediated the relationships between dysphoria and multimorbidity and gait velocity. Overall, our findings indicate that apathy may be an early predictor of motoric cognitive decline. Inflammation plays a modest role, but the underlying biology of apathy warrants further investigation.