AbstractBackgroundRecent literature indicates that apathy is associated with poor cognitive outcomes in community dwelling older adults, including motoric cognitive risk syndrome (MCR), a predementia syndrome defined by subjective cognitive complaints and slow gait. The role of biological markers in the association between apathy and motoric‐cognitive outcomes has not been established. The objectives of this study were to 1) examine the association between inflammation and apathy and 2) to evaluate the moderating effect of inflammation on the association between apathy and motoric‐cognitive outcomes.MethodWe measured apathy in 347 community dwelling older adults enrolled in the Central Control of Mobility in Aging study using an apathy scale score derived from confirmatory factory analysis of the Geriatric Depression Scale Long Form. We conducted cross‐sectional analyses of the following: the association between IL‐6 and CRP with apathy and the moderating effect of IL‐6 on the association between apathy and MCR and slow gait, using logistic regression and linear regression models, respectively. Linear associations were reported using β‐coefficients, while logistic associations were reported using odds ratio (OR) with 95% confidence intervals (CI), adjusting for age, gender, general health status and depression scale score.ResultlogIL‐6 but not logCRP was associated with apathy, in adjusted models (β=.037, 95% CI: .002‐.072, p=.04). Apathy was not significantly associated with MCR at cross‐section (OR: 0.48, 95% CI: .08‐2.97, p=.43), but apathy was significantly associated with gait velocity (β=‐14.45, 95% CI: ‐24.89 ‐ 4.01, p=.01). IL‐6 was associated with gait velocity (β=‐4.48, 95% CI: ‐7.42 ‐ 1.53, p=.003) and moderated the association between apathy and gait velocity by a change in β of 14.5%.ConclusionWe found that IL‐6, but not CRP was associated with apathy in a cohort of community dwelling older adults. Furthermore, IL‐6 moderated the association between apathy and gait velocity, a risk factor for dementia. Apathy was not associated with MCR at cross‐section, despite being associated with incident MCR in prior studies, suggesting that apathy is an early predictor of motoric‐cognitive decline.