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

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.