Table 3.
Worldwide Parkinson’s disease cohorts and IGF-1 levels
| Patients | n | Age (SD) | Sex | Treatment | UPDRS-III stage (SD) | Design | Results | Peripheral blood IGF-1 (ng/ml) PD baseline/controls (SD) | References |
|---|---|---|---|---|---|---|---|---|---|
| Early (< 3.5 years) vs. moderate (> 4 years) PD | 37 | 64 (7) | 15F/22M | Levodopa | 22 (9) (early)/38 (15) (moderate) | Longitudinal prospective cohort (3.5 years)a | PD patients in moderate, but not early stages, showed significantly increased baseline IGF-1 levels. | 130 (26)/106 (24) p = 0.017 | Bernhard et al. [171] |
| Newly diagnosed idiopathic PD (Germany) | 15 | 69 (8.3) | 6F/9M | Drug-naïve | 14.30 (5.3) | Cross-sectional cohorta |
IGF-1 level was higher in patients with PD and inversely correlated with the UPDRS-III score (r = − 0.77) among PD patients IGFBP-3 unchanged IGF-1 level was not related to motor function in the healthy group |
158.4 (40.4)/129.2 (29.1) p = 0.004 | Godau et al. [172] |
| Idiopathic PD (Germany) | 18 | 67 (9) | 8F/22M | Levodopa-treated vs. untreated | 24.1 (8.5) (treated)/16.2 (4.1) (untreated) | Longitudinal (6 months)a |
IGF-1 was significantly higher in treated PD patients than in controls at all time points (all p < 0.001) IGF-1 levels were correlated with shorter disease duration (r = 0.56, p < 0.001) In the patient group, higher IGF-1 levels were correlated with shorter disease duration (r1⁄4 0.56, p1⁄40.001) In the healthy control group, higher IGF-1 levels were correlated with slightly impaired motor performance (r1⁄40.46, p1⁄40.005) In the untreated patient group, IGF-1 levels were significantly higher than healthy controls (p < 0.001) Treatment did not alter GH |
149.06 (30.3)/98.96 (23.2) | Godau et al. [173] |
| PD | 38 | 68 (10) | F and M | – | – | Cross-sectional cohorta | Serum and CSF IGF-1 and IGFBP levels were higher in PD patients than controls (p < 0.001) |
CSF: 5.97 pg/mL (0.93)/4.40 pg/mL (0.58) Serum: 320.19 (40.86)/207.97 (19.51) |
Mashayekhi et al. [174] |
| PD (75), multiple system atrophy (MSA, 25), and progressive supranuclear palsy (PSP, 16) (Japan) | 116 | 68.1 (1.1) | 44F/35M | Drug-naïve vs. levodopa-treated | 26.9 (1.8) | Cross-sectional cohorta |
Serum IGF-1 levels tended to be higher in early PD patients than controls There was a negative correlation between serum IGF-1 levels and age in PD patients and controls There was no significant correlation between disease duration and serum IGF-1 levels in PD patients In controls, there was no significant correlation between serum IGF-1 levels and UPDRS part III In PD and PSP patients, there was a negative correlation between serum IGF-1 levels and UPDRS part III. In early and drug naïve PD patients there was no significant correlation between serum IGF-1 levels and UPDRS part III IGF-1 serum levels in PD patients with HY stage 2 were significantly higher than those in PD patients with HY stages 3–5 |
130.3 (14.6)/114.4 (5.9) | Numao et al. [175] |
| > 3years PD with weight loss (11) vs. PD without weight loss (16) | 27 | 63.5 (8.8)/60.5 (8.6) | 6F, 5M/8F, 8M | Levodopa | 43.45 (17.26)/37.75 (22.17) | Cross-sectional cohorta |
BMI was lower in all PD patients Serum leptin levels were lower in all PD patients Serum GH and IGF-1 levels were higher in all PD patients, mostly in PD with weight loss and without weight loss, respectively Serum active ghrelin levels were positively correlated with serum IGF-1 levels in the control group (p < 0.05; r = 0.67) but not among PD patients |
With weight loss 191.73 (33.84), without weight loss 152.19 (49.62)/144.17 (24.24) (p < 0.05 between PD patients and PD patients with weight loss vs. controls) | Fiszer et al. [176] |
| PD | 25 | 67.9 (9.4) | 5F/20M | Treated, drug not specified | – | Cross-sectional cohorta | IGF-1 and IGFBP-3 serum levels in PD patients showed no correlation with the duration and severity of the disease | 132 (42)/113 (51) | Tuncel et al. [177] |
| Early PD (< 2 years) (Italy) | 65 | 59.7 (8.3) | 26F/39M | Drug-naïve | 14.5 (6.7) | 2-year follow-up prospective cohorta |
At baseline, serum IGF-1 levels were significantly increased as compared to healthy controls A positive correlation between IGF-1 levels and a specific executive function (phonological fluency) assessing cognitive flexibility was found After a 2-year follow-up, IGF-1 levels were positively related to verbal episodic memory, visuoperceptual abilities and attention/executive functions Low IGF-1 levels at baseline were independently associated to poor performance on specific cognitive tasks assessing verbal episodic memory and executive functions after 2 years |
91.6 (34.4)/79.1 (23) (p = 0.019) | Pellecchia et al. [178] |
| Early PD (< 2 years) (Italy) | 37 | 59.4 (9) | 15F/22M | Drug-naïve | 14.6 (7.1) | 12-month follow-up prospective cohorta |
At baseline, serum IGF-1 levels were moderately increased Patients at the highest IGF-1 quartile presented higher mean dopaminergic scores (worse outcome) |
94.5 (37.5)/79.1 (23) (p < 0.011) | Picillo et al. [179] |
| Early PD (< 2 years) | 405 | 61.20 (9.7) | 141F/264M | Drug-naïve | 20.25 (8.93) | 5-year follow-up prospective cohorta |
IGF-1 levels were similar in PD and controls Lower serum IGF-1 levels were associated to poor performances in cognitive tasks assessing executive function, attention and verbal memory |
136.6 (56.1)/134.45 (56.13) | Picillo et al. [180] |
| Meta-analysis covering de novo, drug-naïve idiopathic PD patients | 166 | – | – | Drug-naïve | – | – | Significantly higher serum IGF-1 levels among de novo, drug-naïve idiopathic PD patients at baseline | Li et al. [181] |
HY Hoehn and Yahr score, MDS-UPDRS-III Movement Disease Society-modified UPDRS-III scale, SD standard deviation, UPDRS-III unified Parkinson’s disease rating scale
aAge, sex and body mass index (BMI, kg/m2), as well as the presence or absence of other medical factors known to affect IGF-1 levels, termed medical confounders: diabetes mellitus (reported in medical history or inferred by antidiabetic medication intake), beta-adrenergic medication, depression (and/or antidepressant medication), neuroleptic medication, thyroid dysfunction, inflammatory diseases and cancer. All of them were taken into account when the study was carried out