Apathy as a Predictor of Motoric Cognitive Risk Syndrome

Abstract

AbstractBackgroundApathy is a psychological syndrome, characterized by lack of motivation and interest, flattening of affect, and social withdrawal; that predicts cognitive decline including dementia. Current literature highlights apathy as a separate entity from depression, which is uniquely correlated to cognitive and functional decline in neurologic diseases like stroke and Parkinson’s Disease as well as in community dwelling‐older adults. Further, apathy may mediate the previously described association between depression and cognitive/functional decline. Our objectives were to 1) investigate the association between apathy at baseline and incident predementia syndromes including mild cognitive impairment (MCI) and motoric cognitive risk syndrome (MCR) and 2) explore the direct and indirect relationships of apathy and motoric cognitive outcomes.MethodWe prospectively studied the association between apathy (3‐item subscale of the Geriatric Depression Scale) and incident predementia syndromes in 542 community‐dwelling older adults enrolled in the Central Control of Mobility in Aging study, using Cox proportional hazard models. Associations were reported as hazard ratio (HR) with 95% confidence intervals (CIs), adjusting for age, education, baseline cognitive performance, and dysphoria. In a subset of 347 participants, we examined the mediating role of cytokines on the association between apathy and gait velocity in linear regression models at cross section. We also looked at the mediating role of apathy on the association between dysphoria and multimorbidity and gait velocity.ResultApathy was associated with incident MCR (HR 2.39, 95% CI: 1.10‐5.20), but not MCI. Linear regression models showed that Interleukin‐6 (Il‐6), but not C‐Reactive Protein was significantly associated with apathy adjusted for age, gender, and years of education (B = 0.037, 95% CI: 0.002–0.072, p = 0.04). Apathy was associated with a slower gait velocity (B = 14.45, 95% CI: 24.89–4.01, p = 0.01), cross sectionally. Mediation analyses demonstrated that IL‐6 modestly mediates the relationship between apathy and gait velocity. Additionally, apathy mediated the relationships between dysphoria and multimorbidity and gait velocity.ConclusionOverall, our findings indicate that apathy may be an early predictor of motoric cognitive decline, which precedes predementia syndromes. Inflammation plays a modest role, but the underlying biology of apathy warrants further investigation.