Serum IGF-1 is associated with cognitive functions in early, drug-naïve Parkinson’s disease

Abstract

ObjectiveCognitive deficits are common in Parkinson’s disease (PD) since the early stages and many patients eventually develop dementia. Yet, occurrence of dementia in PD is unpredictable. Evidence supports the hypothesis that insulin-like growth factor-1 (IGF-1) is involved in cognitive deficits. Our aim was to evaluate the relationship between serum IGF-1 levels and neuropsychological scores in a large cohort of drug-naïve PD patients during the earliest stages of the disease.MethodsSerum IGF-1 levels were determined in 405 early, drug-naïve PD patients and 191 healthy controls (HC) enrolled in the Parkinson’s Progression Markers Initiative (PPMI). The association between serum IGF-1 levels and neuropsychological scores was evaluated with linear regression analysis.ResultsIGF-1 levels were similar in PD and HC. In PD patients the lowest IGF-1 quartile was a predictor of lower performances at the Semantic Fluency task (β = -3.46, 95%CI: -5.87 to -1.01, p = 0.005), the Symbol Digit Modalities Score (β = -2.09, 95%CI: -4.02 to -0.15, p = 0.034), and Hopkins Verbal Learning Test Retention (β = -0.05, 95%CI: -0.09 to -0.009, p = 0.019).ConclusionsLower serum IGF-1 levels are associated to poor performances in cognitive tasks assessing executive function, attention and verbal memory in a large cohort of early PD patients. Follow-up studies are warranted to assess if IGF-1 is related to the development of dementia in PD.

Is insulin-like growth factor-1 involved in Parkinson’s disease development?

“…These IGF-1 concentrations inversely correlate with the UPDRS-III score (i.e. with motor function), verbal episodic memory, visuoperceptual abilities and attention/ executive functions; been not found such correlation on healthy subjects [171][172][173][174][175][176][177][178][179][180][181]. As it has been shown, lower IGF-1 levels at the beginning of PD are associated with a worse disease progression and prognosis.…”

Recent Advances in Biomarkers for Parkinson’s Disease

“…In fact, several IGF-1 receptors are reported in many brain regions crucial for cognitive performance, with the highest levels in the frontal cortex and the hippocampus. As a result, the decrease serum IGF-1 concentrations are associated with poor ability in execution and verbal memory in PD patients (Picillo et al, 2017 ). IGF-1 may become a helpful tool for the early detection of PDD.…”

Insulin receptor in the brain: Mechanisms of activation and the role in the CNS pathology and treatment

“…The implication of IR and IR‐related indirect mechanisms was documented during various challenges in adulthood that include aging, neurodegeneration, stress, and exposure to toxins such as alcohol, and are related to the roles of IR in the neuroprotection …”

“…Fundamental roles of the IR‐mediated signaling in brain development are reflected by numerous associations reported between its deficiency and neurodevelopmental disorders, such as autism and schizophrenia, as well as cancer, including cerebellar neoplasms and other syndromes . Altered neuroprotective functions of IR are ascribed to the contribution of IR‐related signaling to the pathophysiology of neurodegenerative diseases, such as Alzheimer's disease, Huntington's disease, and Parkinson's disorder; major depression; and neurotoxicity …”