In a 10-year longitudinal study of 405 early-stage, drug‑naive PD patients, higher baseline serum IGF‑1 was associated with a slower progression of anxiety symptoms, with middle and high tertiles showing significantly reduced anxiety worsening over time.

While observational and lacking mechanistic detail, the result highlights IGF‑1 as a promising prognostic biomarker and a candidate pathway for developing neuroprotective or symptom‑modifying interventions targeting non‑motor features in PD.

OBJECTIVE: Insulin-like growth factor-1 (IGF-1), a neuroprotective polypeptide, has been implicated in the pathophysiology of Parkinson's disease (PD). Although cross-sectional studies have reported an inverse relationship between serum IGF-1 levels and anxiety in PD patients, the longitudinal effects of IGF-1 on anxiety symptoms remain unclear. METHODS: A total of 405 early-stage, drug-naive PD patients and 191 matched healthy controls from the Parkinson's Progression Markers Initiative (PPMI) database were included in this study. In the PD cohort, linear mixed-effects (LME) models were used to examine the association between baseline IGF-1 levels (analyzed as both continuous and categorical variables) and longitudinal changes in State-Trait Anxiety Inventory (STAI) scores over 10 years. RESULTS: Among the 405 drug-naive, early-stage PD patients, 64.9% were male. At baseline, the mean age was 61.68 ± 9.74 years, mean disease duration was 0.55 ± 0.55 years, and mean STAI score was 65.36 ± 18.38. Median baseline IGF-1 levels were 126.5 ng/mL in PD patients (n = 405) and 118.8 ng/mL in healthy controls (n = 191), with no significant difference (p = 0.457). After adjusting for covariates, the LME model treating IGF-1 as a continuous variable showed no significant association with baseline STAI scores. However, the IGF-1 × time interaction was significant (β = -0.003, p = 0.038), suggesting that higher IGF-1 levels were associated with a slower progression of anxiety symptoms over time. Similarly, in the tertile model, the middle and high IGF-1 groups showed significantly slower progression of anxiety over 10 years (Group × Time interaction: β = -0.79 and - 0.70; p < 0.001). CONCLUSION: This study provided longitudinal evidence of a negative association between serum IGF-1 levels and the progression of anxiety symptoms in PD patients, which may serve as a potential biomarker for the progression of anxiety symptoms in PD.