Peripheral Inflammation and Cognitive Decline in Early Parkinson’s Disease: The Roles of IL-6 and TNF-α

Abstract

Cognitive decline is a significant non-motor symptom that often emerges early in Parkinson’s disease (PD), yet its underlying causes remain unclear. Growing evidence suggests that peripheral inflammation may play an important role, particularly through elevated levels of cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). This literature review explores studies examining the link between IL-6, TNF-α, and cognitive impairment in early-stage PD. Findings indicate that higher IL-6 levels are consistently associated with poorer cognitive performance, while TNF-α shows a weaker but still notable correlation. These cytokines may contribute to neurodegeneration through mechanisms like microglial activation and blood-brain barrier disruption. However, much of the evidence is cross-sectional, making it unclear whether inflammation causes cognitive decline or simply reflects disease severity. Future longitudinal research is needed to clarify causality and determine whether targeting inflammation could help slow or prevent cognitive decline in PD.