Abstract
IntroductionBiomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's disease (PD) often lack specificity or reliability. Investigating biomarker variance between individuals and over time and the effect of confounding factors is essential for the evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1).Materials and MethodsIGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22 healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual changes in IGF-1 were compared between PD patients and HC while accounting for baseline disease duration (19 early stage: ≤3.5 years; 18 moderate stage: >4 years), age, sex, body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition, associations of baseline IGF-1 with annual changes of motor, cognitive and depressive symptoms and medication dose were investigated.ResultsPD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1), showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL; p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47, p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were not associated with annual changes of clinical parameters.DiscussionElevated IGF-1 in serum might differentiate between patients in moderate PD stages and HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated by several confounders.
Highlights
Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's disease (PD) often lack specificity or reliability
When considering the PD stage for the grouping of PD patients, only M-PD (130 ± 26 ng/mL, adjusted for covariates, t38 = 3.03, p = .004), but not E-PD (115 ± 19 ng/mL, p > .1) showed significantly increased insulin-like growth factor 1 (IGF-1) baseline levels compared with healthy controls (HC) (106 ± 24 ng/mL)
We evaluated the potential of IGF-1 (1) in differentiating PD patients in early and moderate stages from healthy controls (HC, trait marker), (2) for indicating differences in longitudinal IGF-1 changes in PD and HC, and (3) for its prediction of changes in PD symptoms over time
Summary
Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's disease (PD) often lack specificity or reliability. For complex and progressive diseases, such as Parkinson's disease (PD), interindividual heterogeneity of patients regarding genetic background, life-style and environmental factors, disease stage, age of onset and severity of (sub) symptoms, comorbidities, and pharmacological or other interventions are clinically relevant [4,5] In addition to these interindividual differences of PD patients, methodological issues at the stages of biomarker assessment, processing, analysis, interpretation and consideration of confounding factors (e.g., age, sex, body mass index (BMI), diabetes mellitus, thyroid dysfunction, β-adrenergic medication, depression/anti-depressant medication, inflammatory diseases and cancer) [1,6,7,8,9] may challenge the identification of reliable and valid biomarkers in PD. Biomarker variance between PD patients and over time, as well as the effect of potential confounders, should be characterized to increase the diagnostic and prognostic value of PD biomarkers
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