| 1. |
- Gadd, Gustaf, et al.
(författare)
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A Nonlinear Relation between Body Mass Index and Long-Term Poststroke Functional Outcome-The Importance of Insulin Resistance, Inflammation, and Insulin-like Growth Factor-Binding Protein-1.
- 2024
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Ingår i: International journal of molecular sciences. - 1661-6596 .- 1422-0067. ; 25:9
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Tidskriftsartikel (refereegranskat)abstract
- Both high serum insulin-like growth factor-binding protein-1 (s-IGFBP-1) and insulin resistance (IR) are associated with poor functional outcome poststroke, whereas overweight body mass index (BMI; 25-30) is related to fewer deaths and favorable functional outcome in a phenomenon labeled "the obesity paradox". Furthermore, IGFBP-1 is inversely related to BMI, in contrast to the linear relation between IR and BMI. Here, we investigated s-IGFBP-1 and IR concerning BMI and 7-year poststroke functional outcome. We included 451 stroke patients from the Sahlgrenska Study on Ischemic Stroke (SAHLSIS) with baseline measurements of s-IGFBP1, homeostasis model assessment of IR (HOMA-IR), BMI (categories: normal-weight (8.5-25), overweight (25-30), and obesity (>30)), and high-sensitivity C-reactive protein (hs-CRP) as a measure of general inflammation. Associations with poor functional outcome (modified Rankin scale [mRS] score: 3-6) after 7 years were evaluated using multivariable binary logistic regression, with overweight as reference due to the nonlinear relationship. Both normal-weight (odds-ratio [OR] 2.32, 95% confidence interval [CI] 1.30-4.14) and obese (OR 2.25, 95% CI 1.08-4.71) patients had an increased risk of poor functional outcome, driven by deaths only in the normal-weight. In normal-weight, s-IGFBP-1 modestly attenuated (8.3%) this association. In the obese, the association was instead attenuated by HOMA-IR (22.4%) and hs-CRP (10.4%). Thus, a nonlinear relation between BMI and poor 7-year functional outcome was differently attenuated in the normal-weight and the obese.
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| 2. |
- Horvath, Alexandra, et al.
(författare)
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Low Serum Insulin-like Growth Factor-I Is Associated with Decline in Hippocampal Volume in Stable Mild Cognitive Impairment but not in Alzheimer's Disease
- 2022
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 88:3, s. 1007-1016
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Tidskriftsartikel (refereegranskat)abstract
- Background: Serum insulin-like growth factor-I (IGF-I) has shown some association with hippocampal volume in healthy subjects, but this relation has not been investigated in stable mild cognitive impairment (sMCI) or Alzheimer's disease (AD). Objective: At a single memory clinic, we investigated whether serum IGF-I was associated with baseline magnetic resonance imaging (MRI)-estimated brain volumes and longitudinal alterations, defined as annualized changes, up to 6 years of followup. Methods: A prospective study of patients with sMCI (n = 110) and AD (n = 60). Brain regions included the hippocampus and amygdala as well as the temporal, parietal, frontal, and occipital lobes, respectively. Results: Serum IGF-I was statistically similar in sMCI and AD patients (112 versus 123 ng/mL, p = 0.31). In sMCI, serum IGF-I correlated positively with all baseline MRI variables except for the occipital lobe, and there was also a positive correlation between serum IGF-I and the annualized change in hippocampal volume ( rs = 0.32, p = 0.02). Furthermore, sMCI patients having serum IGF-I above the median had lower annual loss of hippocampal volume than those with IGF-I below the median (p = 0.02). In contrast, in AD patients, IGF-I did not associate with baseline levels or annualized changes in brain volumes. Conclusion: In sMCI patients, our results suggest that IGF-I exerted neuroprotective effects on the brain, thereby maintaining hippocampal volume. In AD, serum IGF-I did not associate with brain volumes, indicating that IGF-I could not induce neuroprotection in this disease. This supports the notion of IGF-I resistance in AD.
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| 3. |
- Horvath, Alexandra, et al.
(författare)
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The Associations Between Serum Insulin-like Growth Factor-I, Brain White Matter Volumes, and Cognition in Mild Cognitive Impairment and Alzheimer's Disease
- 2024
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Ingår i: JOURNAL OF ALZHEIMERS DISEASE. - 1387-2877 .- 1875-8908. ; 99:2, s. 609-622
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Tidskriftsartikel (refereegranskat)abstract
- Background: Insulin-like growth factor-I (IGF-I) regulates myelin, but little is known whether IGF-I associates with white matter functions in subjective and objective mild cognitive impairment (SCI/MCI) or Alzheimer's disease (AD). Objective: To explore whether serum IGF-I is associated with magnetic resonance imaging - estimated brain white matter volumes or cognitive functions. Methods: In a prospective study of SCI/MCI (n = 106) and AD (n = 59), we evaluated the volumes of the total white matter, corpus callosum (CC), and white matter hyperintensities (WMHs) as well as Mini-Mental State Examination (MMSE), Trail Making Test A and B (TMT-A/B), and Stroop tests I-III at baseline, and after 2 years. Results: IGF-I was comparable in SCI/MCI and AD (113 versus 118 ng/mL, p = 0.44). In SCI/MCI patients, the correlations between higher baseline IGF-I and greater baseline and 2-year volumes of the total white matter and total CC lost statistical significance after adjustment for intracranial volume and other covariates. However, after adjustment for covariates, higher baseline IGF-I correlated with better baseline scores of MMSE and Stroop test II in SCI/MCI and with better baseline results of TMT-B and Stroop test I in AD. IGF-I did not correlate with WMH volumes or changes in any of the variables. Conclusions: Both in SCI/MCI and AD, higher IGF-I was associated with better attention/executive functions at baseline after adjustment for covariates. Furthermore, the baseline associations between IGF-I and neuropsychological test results in AD may argue against significant IGF-I resistance in the AD brain.
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| 4. |
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| 5. |
- Stanne, Tara M, 1979, et al.
(författare)
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Low Circulating Acute Brain-Derived Neurotrophic Factor Levels Are Associated With Poor Long-Term Functional Outcome After Ischemic Stroke.
- 2016
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Ingår i: Stroke; a journal of cerebral circulation. - 1524-4628 .- 0039-2499. ; 47:7, s. 1943-1945
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Tidskriftsartikel (refereegranskat)abstract
- Brain-derived neurotrophic factor (BDNF) plays important roles in brain plasticity and repair, and it influences stroke outcomes in animal models. Circulating BDNF concentrations are lowered in patients with traumatic brain injury, and low BDNF predicts poor recovery after this injury. We sought to investigate whether circulating concentrations of BDNF are altered in the acute phase of ischemic stroke and whether they are associated with short- or long-term functional outcome.
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| 6. |
- Wall, Alexander, et al.
(författare)
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Circulating granulocyte colony-stimulating factor and functional outcome after ischemic stroke: an observational study
- 2021
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Ingår i: Neurological Research. - : Informa UK Limited. - 0161-6412 .- 1743-1328. ; 43:12, s. 1013-1022
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: While granulocyte colony-stimulating factor (G-CSF) has shown beneficial effects in experimental ischemic stroke (IS), these effects have not been reproduced clinically. Small-to-medium-sized observational studies have reported varying associations for G-CSF with stroke severity and post-stroke functional outcome, prompting their investigation in a larger study. Methods: Endogenous serum G-CSF (S-GCSF) was measured in the acute phase and after 3 months in patients with IS (N = 435; 36% females; mean age, 57 years) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Stroke severity was scored according to the National Institutes of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) assessed functional outcomes at 3-month and 2-year post-stroke. Correlation and logistic regression analyses with confounder adjustments assessed the relationships. Results: The acute S-GCSF level was 23% higher than at 3-month post-stroke (p < 0.001). Acute G-CSF correlated weakly with stroke severity quintiles (r = 0.12, p = 0.013) and with high-sensitivity C-reactive protein (r = 0.29, p < 0.001). The association between S-GCSF (as quintiles, q) and poor functional outcome at 3 months (mRS 3-6; S-GCSF-q5 vs. S-GCSF-q1, age- and sex-adjusted odds ratio: 4.27, 95% confidence interval: 1.82-9.99; p = 0.001) withstood adjustment for cardiovascular risk factors and stroke subtype, but not additional correction for stroke severity. Post-stroke changes in S-GSCF and absolute 3-month S-GCSF were not associated with 3-month or 2-year functional outcomes. Discussion: Early post-stroke S-GCSF is increased in severe IS and associated with 3-month poor functional outcomes. The change in S-GCSF and the 3-month S-GCSF appear to be less-important, and S-GCSF likely reflects inflammation in large infarctions.
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| 7. |
- Wall, Alexander, et al.
(författare)
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Exercise and health-related quality of life and work-related outcomes in primary care patients with anxiety disorders - A randomized controlled study
- 2024
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Ingår i: JOURNAL OF AFFECTIVE DISORDERS. - 0165-0327 .- 1573-2517. ; 360, s. 5-14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Exercise interventions show promise in the treatment of anxiety disorders, but effects on healthrelated quality of life (HR-QoL), work ability, and sick leave are little studied. We investigated these outcomes in a 12-week randomized controlled trial with a 1-year follow-up. Methods: Patients aged 18-65 (n = 222) with anxiety disorders from primary care centers in Gothenburg were randomized to a control group or one of two 12-week exercise intervention groups (low-intensity, [LI] and moderate/high-intensity, [HI]); 148 were evaluated at 12-weeks and 113 completed the 1-year follow-up. The EuroQol 5D (EQ5D; index and the visual analogue scale [VAS]), work ability score (WAS), presenteeism, and selfreported sick leave were assessed at baseline, 12 weeks, and 1 year. Improvements were defined by binary cutoffs for each scale. Binary logistic regression with odds ratios (OR) and 95 % confidence intervals (CI) were reported. Results: There were improved scores for EQ5D and WAS in the HI group compared to controls after 12 weeks (EQ5D index: 4.74 [1.91-11.7], EQ5D-VAS 4.00, [1.65-9.72], WAS 3.41 [1.24-7.37]) and 1 year (EQ5D index: 3.05 [1.05-8.81], EQ5D-VAS 3.20 [1.16-8.84], WAS 5.50 [1.85-16.3]). Post-hoc analysis showed higher ORs in participants on antidepressants (n = 75) (12-week EQ5D index: OR 9.95 [2.85-34.8]) and significant improvements in EQ5D scores for both intervention groups after 1 year. There were no between-group differences for presenteeism or sick leave. Limitations: Discontinuation was high, mostly early after randomization (n = 74), as is common for anxiety interventions. Conclusions: HI Exercise improves HR-QoL and work ability in anxiety patients, especially when combined with antidepressants.
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| 8. |
- Walser, Marion, 1961, et al.
(författare)
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Different modes of GH administration influence gene expression in the male rat brain
- 2014
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Ingår i: Journal of Endocrinology. - 0022-0795 .- 1479-6805. ; 222:2, s. 181-190
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Tidskriftsartikel (refereegranskat)abstract
- The endogenous secretion pattern in males of GH is episodic in rats and in humans, whereas GH administration is usually even. Different types of GH administration have different effects on body mass, longitudinal bone growth, and liver metabolism in rodents, whereas possible effects on brain plasticity have not been investigated. In this study, GH was administered as a continuous infusion or as two daily injections in hypophysectomized male rats. Thirteen transcripts previously known to respond to GH in the hippocampus and parietal cortex (cortex) were assessed by RT-PCR. To investigate the effects of type of GH administration on several transcripts with different variations, and categories of transcripts (neuron-, glia-, and GH-related), a mixed model analysis was applied. Accordingly, GH injections increased overall transcript abundance more than GH infusions (21% in the hippocampus, P<0.001 and 10% in the cortex, PZ0.09). Specifically, GH infusions and injections robustly increased neuronal hemoglobin beta (Hbb) expression significantly (1.8- to 3.6-fold), and GH injections were more effective than GH infusions in increasing Hbb in the cortex (41%, PZ0.02), whereas a 23% difference in the hippocampus was not significant. Also cortical connexin 43 was higher in the group with GH injections than in those with GH infusions (26%, P<0.007). Also, there were differences between GH injections and infusions in GH-related transcripts of the cortex (23%, PZ0.04) and glia-related transcripts of the hippocampus (15%, PZ0.02). Thus, with the exception of Hbb there is a moderate difference in responsiveness to different modes of GH administration. © 2014 Society for Endocrinology.
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| 9. |
- Walser, Marion, 1961, et al.
(författare)
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Effects of peripheral administration of GH and IGF-I on gene expression in the hippocampus of hypophysectomised rats
- 2018
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Ingår i: Neuroendocrinology Letters. - 0172-780X. ; 39:7, s. 525-531
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Growth hormone (GH) increases insulin-like growth factor I (IGF-I) production and both hormones affect hippocampal plasticity. We have previously shown that Hbb and Alas2 in the rat hippocampus were robustly regulated by GH-infusions for six days, whereas other transcripts were weakly affected. Here, weexplored the effects of prolonged GH administration on transcripts linked to neuroprotection and investigated whether serum IGF-I administration may exert similar effects. DESIGN: Hypophysectomised female rats were infused with GH or IGF-I for 19 days. Hbb, Alas2 and seven additional GH- and IGF-I-related transcripts were quantified by Q-RT-PCR in rat hippocampus. RESULTS: Three transcripts, Hbb, Alas2, and Aloxl5 were increased by both GH and IGF-I administration. The other transcripts were marginally affected. CONCLUSION: The 19-day GH-infusion induced similar effects as those reported after 6-day GH treatment, with the addition of the regulation of transcript Aloxl5. IGF-I induced altered gene expression in relation to its effect on weight gain. This study underlines that there is an entity of transcripts involved in neuroprotection and vascular tone that is regulated by both systemic GH and IGF-I. For other transcripts, the longer duration of this study did not significantly enhance the marginal effects of GH administration seen previously. © 2018 Neuroendocrinology Letters
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| 10. |
- Walser, Marion, 1961, et al.
(författare)
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Growth Hormone and Neuronal Hemoglobin in the Brain-Roles in Neuroprotection and Neurodegenerative Diseases
- 2021
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, evidence for hemoglobin (Hb) synthesis in both animal and human brains has been accumulating. While circulating Hb originating from cerebral hemorrhage or other conditions is toxic, there is also substantial production of neuronal Hb, which is influenced by conditions such as ischemia and regulated by growth hormone (GH), insulin-like growth factor-I (IGF-I), and other growth factors. In this review, we discuss the possible functions of circulating and brain Hb, mainly the neuronal form, with respect to the neuroprotective activities of GH and IGF-I against ischemia and neurodegenerative diseases. The molecular pathways that link Hb to the GH/IGF-I system are also reviewed, although the limited number of reports on this topic suggests a need for further studies. In summary, GH and/or IGF-I appear to be significant determinants of systemic and local brain Hb concentrations through mediating responses to oxygen and metabolic demand, as part of the neuroprotective effects exerted by GH and IGF-I. The nature and quantity of the latter deserve further exploration in specific experiments.
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