Peripheral inflammation’s variable impact on cognitive and symptomatic outcomes in Parkinson’s disease: a longitudinal and cross-sectional analysis

Increasing evidence supported a link between peripheral inflammation and Parkinson's disease (PD). However, the role of peripheral inflammation in the progression of PD clinical symptoms remained unclear. This study evaluates peripheral inflammation using serum differential leukocyte counts and their derived ratios. A total of 170 PD patients were retrospectively enrolled from Guangdong Provincial People's Hospital (GDPH) and 68 from PPMI. Partial correlation analysis showed that neutrophil-to-lymphocyte ratio (NLR) negatively correlated with MoCA in GDPH but not in PPMI. Moreover, peripheral inflammation was shown to correlate with white matter integrity. The result of the longitudinal analysis showed that higher baseline NLR predicted worsening in letter number sequencing (LNS) score. Path analysis indicated that white matter integrity significantly mediated the relationship between NLR and cognitive change in the LNS score from Year 5 to baseline. Peripheral inflammation is associated with global cognition and white matter integrity in PD and predicts cognitive decline.