Correlation Between Cognitive Function and Serum Irisin Levels in Parkinson's Disease Patients

Cognitive impairment is a common non-motor symptom of Parkinson's disease (PD) that markedly reduces patients' quality of life. Given the clinical heterogeneity of PD-related cognitive impairment (PDCI), further clarification of clinical and circulating biological factors associated with cognitive status may help improve our understanding of cognitive dysfunction in PD.

In this cross-sectional study, 243 patients with PD and 90 age- and sex-matched healthy controls (HCs) were enrolled. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA), and patients with PD were classified into the PD with cognitive impairment (PDCI) and PD without cognitive impairment (PDNCI) groups. Based on motor symptoms, PD patients were further divided into three subtypes: tremor-dominant (TD), postural instability and gait disorder (PIGD), and indeterminate subtype (IND). Group comparisons and logistic regression analyses were performed to examine factors associated with cognitive impairment.

Serum irisin levels did not differ significantly between patients with PD and healthy controls (p = 0.478). Compared with PDNCI patients, those with PDCI had lower serum irisin levels. Among motor subtypes, the PIGD group showed a higher prevalence of cognitive impairment (68.8% vs. 46.2%, p < 0.001) and significantly lower irisin levels compared with the TD group [3.25 (2.62-4.14) vs. 4.12 (3.42-5.07) µg/mL, p < 0.001]. Serum irisin levels were weakly but positively associated with memory performance, and this association remained significant after FDR correction across the five cognitive domains (r = 0.194, FDR-adjusted p = 0.010). Compared with patients in the TD-high irisin group, those in the PIGD-low irisin group had higher odds of concurrent cognitive impairment (OR = 6.065, 95% CI: 2.974-18.638, p = 0.002).

Cognitive impairment was common among patients with PD, particularly those with the PIGD subtype. The PIGD subtype and lower serum irisin levels were associated with the presence of PDCI. In the joint-category analysis, patients in the PIGD-low-irisin group had higher odds of concurrent cognitive impairment than those in the TD-high-irisin group.