Changes of plasma cGP/IGF-1 molar ratio with age is associated with cognitive status of Parkinson disease

Abstract

Objective: Cognitive impairment is a common feature of Parkinson disease (PD), for which age is a major contributing factor. Insulin-like growth factor-1 (IGF-1) declines with age and contributes to age-related cognitive impairment in PD. Cyclic glycine-proline (cGP) is a metabolite of IGF-1 and normalizes bioavailable IGF-1. Plasma cGP/IGF-1 molar ratio that represents bioactive IGF-1 in circulation, may associate with the cognitive status in PD. Methods: We examined the association of plasma cGP/IGF-1 molar ratio with the cognitive scores or age in PD patients with normal cognition (PD-N, n = 74), mild cognitive impairment (PD-MCI, n = 71), or dementia (PD-D, n = 33), and with the cognitive scores in 23 age-matched healthy controls. Plasma concentrations of IGF-1, IGF binding protein-3, and cGP were evaluated using enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography-mass spectrometry (HPLC-MS), respectively. Results: The cGP/IGF-1 molar ratio was positively correlated with the age of PD-N group, negatively correlated with the age of PD-D group, and not associated with the age of PD-MCI group. Independent of age, the cGP/IGF-1 molar ratio was positively correlated with the cognitive scores of healthy controls, but not in PD groups. Conclusion: Old healthy people with a higher cGP/IGF-1 molar ratio showed better preserved cognition, possibly due to improved IGF-1 function. Increased cGP/IGF-1 molar ratio with age may contribute to cognitive retention in the PD-N group. The absence or reversal of such association with age in the PD-MCI and PD-D groups may indicate the conversion of cognitive status in PD, if confirmed through longitudinal investigations within the individuals with advancing cognitive impairment.