Association between IGFBP-3 and longitudinal neuropsychiatric symptom trajectories in early Parkinson's disease: a longitudinal cohort study.

BACKGROUND

Neuropsychiatric symptoms are common in Parkinson's disease (PD), yet biomarkers associated with their long-term progression remain poorly characterized. Insulin-like growth factor binding protein-3 (IGFBP-3) is involved in neurotrophic and metabolic processes. We examined whether baseline IGFBP-3 was associated with subsequent anxiety and depressive symptom trajectories in patients with early PD.

METHODS

This longitudinal cohort included 352 patients with early-stage PD followed annually for up to 7 years. Anxiety and depressive symptoms were assessed using the State-Trait Anxiety Inventory (STAI) and 15-item Geriatric Depression Scale (GDS), respectively. Linear mixed-effects models evaluated IGFBP-3 × time interactions, with adjustment for demographic, disease-related, metabolic, systemic, and treatment-related covariates, including time-varying levodopa-equivalent daily dose.

RESULTS

In fully adjusted longitudinal models, each 1-SD higher baseline IGFBP-3 was associated with a slower annual increase in STAI (β=-0.41 points/year; 95% CI, - 0.60 to - 0.22; P < 0.001) and GDS scores (β=-0.055 points/year; 95% CI, - 0.082 to - 0.028; P < 0.001). By Year 7, adjusted STAI scores were 68.5 in the low and 63.4 in the high IGFBP-3 tertile, corresponding to a difference of 5.1 points (95% CI, 2.8-7.4; P < 0.001); corresponding GDS scores were 3.17 and 2.36. After mutual adjustment, the IGFBP-3 × time association remained evident for STAI (β=-0.36; 95% CI, - 0.57 to - 0.15; P = 0.001) and GDS (β=-0.049; 95% CI, - 0.079 to - 0.019; P = 0.002). The molar IGF-1/IGFBP-3 ratio was not associated with longitudinal changes in STAI (P = 0.433) or GDS (P = 0.498).

CONCLUSIONS

Higher baseline IGFBP-3 was associated with slower progression of anxiety and depressive symptoms over 7 years in early PD, suggesting that IGFBP-3 may capture clinically relevant information on neuropsychiatric symptom progression.