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- Snellman, Anniina, et al.
(författare)
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ASIC-E4: Interplay of Beta-Amyloid, Synaptic Density and Neuroinflammation in Cognitively Normal Volunteers With Three Levels of Genetic Risk for Late-Onset Alzheimer's Disease - Study Protocol and Baseline Characteristics
- 2022
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background:& nbsp;Detailed characterization of early pathophysiological changes in preclinical Alzheimer's disease (AD) is necessary to enable development of correctly targeted and timed disease-modifying treatments. ASIC-E4 study ( "Beta-Amyloid, Synaptic loss, Inflammation and Cognition in healthy APOE epsilon 4 carriers ") combines state-of-the-art neuroimaging and fluid-based biomarker measurements to study the early interplay of three key pathological features of AD, i.e., beta-amyloid (A beta) deposition, neuroinflammation and synaptic dysfunction and loss in cognitively normal volunteers with three different levels of genetic (APOE-related) risk for late-onset AD.& nbsp;Objective:& nbsp;Here, our objective is to describe the study design, used protocols and baseline demographics of the ASIC-E4 study.& nbsp;Methods/Design:& nbsp;ASIC-E4 is a prospective observational multimodal imaging study performed in Turku PET Centre in collaboration with University of Gothenburg. Cognitively normal 60-75-year-old-individuals with known APOE epsilon 4/epsilon 4 genotype were recruited via local Auria Biobank (Turku, Finland). Recruitment of the project has been completed in July 2020 and 63 individuals were enrolled to three study groups (Group 1: APOE epsilon 4/epsilon 4, N = 19; Group 2: APOE epsilon 4/epsilon 3, N = 22; Group 3: APOE epsilon 3/epsilon 3, N = 22). At baseline, all participants will undergo positron emission tomography imaging with tracers targeted against A beta deposition (C-11-PIB), activated glia (C-11-PK11195) and synaptic vesicle glycoprotein 2A (C-11-UCB-J), two brain magnetic resonance imaging scans, and extensive cognitive testing. In addition, blood samples are collected for various laboratory measurements and blood biomarker analysis and cerebrospinal fluid samples are collected from a subset of participants based on additional voluntary informed consent. To evaluate the predictive value of the early neuroimaging findings, neuropsychological evaluation and blood biomarker measurements will be repeated after a 4-year follow-up period.& nbsp;Discussion:& nbsp;Results of the ASIC-E4 project will bridge the gap related to limited knowledge of the synaptic and inflammatory changes and their association with each other and A beta in "at-risk " individuals. Thorough in vivo characterization of the biomarker profiles in this population will produce valuable information for diagnostic purposes and future drug development, where the field has already started to look beyond A beta.
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- Pham, T. T., et al.
(författare)
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Human Bone Marrow Adipose Tissue is a Metabolically Active and Insulin-Sensitive Distinct Fat Depot
- 2020
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 105:7, s. 2300-2310
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Bone marrow (BM) in adult long bones is rich in adipose tissue, but the functions of BM adipocytes are largely unknown. We set out to elucidate the metabolic and molecular characteristics of BM adipose tissue (BMAT) in humans. OBJECTIVE: Our aim was to determine if BMAT is an insulin-sensitive tissue, and whether the insulin sensitivity is altered in obesity or type 2 diabetes (T2DM). DESIGN: This was a cross-sectional and longitudinal study. SETTING: The study was conducted in a clinical research center. PATIENTS OR OTHER PARTICIPANTS: Bone marrow adipose tissue glucose uptake (GU) was assessed in 23 morbidly obese subjects (9 with T2DM) and 9 healthy controls with normal body weight. In addition, GU was assessed in another 11 controls during cold exposure. Bone marrow adipose tissue samples for molecular analyses were collected from non-DM patients undergoing knee arthroplasty. INTERVENTION(S): Obese subjects were assessed before and 6 months after bariatric surgery and controls at 1 time point. MAIN OUTCOME MEASURE: We used positron emission tomography imaging with 2-[18F]fluoro-2-deoxy-D-glucose tracer to characterize GU in femoral and vertebral BMAT. Bone marrow adipose tissue molecular profile was assessed using quantitative RT-PCR. RESULTS: Insulin enhances GU in human BMAT. Femoral BMAT insulin sensitivity was impaired in obese patients with T2DM compared to controls, but it improved after bariatric surgery. Furthermore, gene expression analysis revealed that BMAT was distinct from brown and white adipose tissue. CONCLUSIONS: Bone marrow adipose tissue is a metabolically active, insulin-sensitive and molecularly distinct fat depot that may play a role in whole body energy metabolism. © Endocrine Society 2020.
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- Pulli, E. P., et al.
(författare)
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Prenatal exposures and infant brain: Review of magnetic resonance imaging studies and a population description analysis
- 2019
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 40:6, s. 1987-2000
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Tidskriftsartikel (refereegranskat)abstract
- Brain development is most rapid during the fetal period and the first years of life. This process can be affected by many in utero factors, such as chemical exposures and maternal health characteristics. The goal of this review is twofold: to review the most recent findings on the effects of these prenatal factors on the developing brain and to qualitatively assess how those factors were generally reported in studies on infants up to 2 years of age. To capture the latest findings in the field, we searched articles from PubMed 2012 onward with search terms referring to magnetic resonance imaging (MRI), brain development, and infancy. We identified 19 MRI studies focusing on the effects of prenatal environment and summarized them to highlight the recent advances in the field. We assessed population descriptions in a representative sample of 67 studies and conclude that prenatal factors that have been shown to affect brain metrics are not generally reported comprehensively. Based on our findings, we propose some improvements for population descriptions to account for plausible confounders and in time enable reliable meta-analyses to be performed. This could help the pediatric neuroimaging field move toward more reliable identification of biomarkers for developmental outcomes and to better decipher the nuances of normal and abnormal brain development.
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- Virtanen, KA, et al.
(författare)
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Differential effects of rosiglitazone and metformin on adipose tissue distribution and glucose uptake in type 2 diabetic subjects
- 2003
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 52:2, s. 283-290
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the effects of rosiglitazone (4 mg b.i.d.) and metformin (1 g b.i.d.) monotherapy for 26 weeks on adipose tissue insulin-stimulated glucose uptake in patients (n = 41) with type 2 diabetes. Before and after the treatment, glucose uptake was measured using 2-[18F]fluoro-2-deoxyglucose and positron emission tomography and adipose tissue masses were quantified using magnetic resonance imaging. Rosiglitazone improved insulin-stimulated whole-body glucose uptake by 44% (P < 0.01 vs. placebo). Mean body weight was unchanged in the rosiglitazone group, while it decreased by 2.0 kg in the metformin group (P < 0.05 vs. placebo). In visceral adipose tissue, glucose uptake increased by 29% (from 17.8 ± 2.0 to 23.0 ± 2.6 μmol · kg−1 · min−1, P < 0.05 vs. placebo) in the rosiglitazone group but to a lesser extent (17%) in the metformin group (from 16.2 ± 1.5 to 18.9 ± 1.7 μmol · kg−1 · min−1, P < 0.05 vs. baseline). Because the visceral adipose tissue mass simultaneously decreased with both treatments (P < 0.05), no change was observed in total visceral glucose uptake per depot. Rosiglitazone significantly enhanced glucose uptake in the femoral subcutaneous area, either when expressed per tissue mass (from 10.8 ± 1.2 to 17.1 ± 1.7 μmol · kg−1 · min−1, P < 0.01 vs. placebo) or per whole-fat depot (P < 0.05 vs. placebo). In conclusion, metformin treatment resulted in improvement of glycemic control without enhancement of peripheral insulin sensitivity. The improved insulin sensitivity of the nonabdominal subcutaneous adipose tissue during treatment with rosiglitazone partly explains the enhanced whole-body insulin sensitivity and underlies the central role of adipose tissue for action of peroxisome proliferator-activated receptor γ agonist in vivo.
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- Hannukainen, J, et al.
(författare)
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In Vivo Measurements of Glucose Uptake in Human Achilles Tendon During Different Exercise Intensities
- 2005
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Ingår i: International Journal of Sports Medicine. - : Georg Thieme Verlag KG. - 0172-4622 .- 1439-3964. ; 26, s. 727-731
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Tidskriftsartikel (refereegranskat)abstract
- Muscular contraction and loading of adjacent tendons has been demonstrated to cause increased blood flow and metabolic activity in the peritendinous region. However, it is poorly known to what extent the human tendon itself takes up glucose during exercise. Thus, the purpose of this study was to measure tendon glucose uptake with increasing exercise intensity and to compare it to muscle glucose uptake at the same intensities. Eight young men were examined on three separate days during which they performed 35 min of cycling at 30, 55 and 75 % of VO2max, respectively. Glucose uptake was measured directly by positron emission tomography (PET) with 2-[ (18)F]fluoro-2-deoxyglucose ([18F]FDG). [18F]FDG was injected after 10 min of exercise that was continued for a further 25 min after the injection. PET scanning of the thigh and Achilles region was performed after the exercise. Glucose uptake of the Achilles tendon (AT) remained unchanged (7.1 +/- 1.5, 6.6 +/- 1.1, and 6.0 +/- 1.1 micromol.kg(-1).min(-1)) with the increasing workload, although the glucose uptake in m. quadriceps femoris simultaneously clearly increased (48 +/- 35, 120 +/- 35, and 152 +/- 74 micromol.kg(-1).min(-1), p < 0.05). In conclusion, the AT takes up glucose during exercise but in significantly smaller amounts than the skeletal muscle does. Furthermore, glucose uptake in the AT is not increased with the increasing exercise intensity. This may be partly explained by the cycle ergometry exercise used in the present study, which probably causes only a little increase in strain to the AT with increasing exercise intensity.
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- Koffert, J. P., et al.
(författare)
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Metformin treatment significantly enhances intestinal glucose uptake in patients with type 2 diabetes: Results from a randomized clinical trial
- 2017
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 131, s. 208-216
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Tidskriftsartikel (refereegranskat)abstract
- Aims Metformin therapy is associated with diffuse intestinal 18F-fluoro-deoxyglucose (FDG) accumulation in clinical diagnostics using routine FDG-PET imaging. We aimed to study whether metformin induced glucose uptake in intestine is associated with the improved glycaemic control in patients with type 2 diabetes. Therefore, we compared the effects of metformin and rosiglitazone on intestinal glucose metabolism in patients with type 2 diabetes in a randomized placebo controlled clinical trial, and further, to understand the underlying mechanism, evaluated the effect of metformin in rats. Methods Forty-one patients with newly diagnosed type 2 diabetes were randomized to metformin (1g, b.i.d), rosiglitazone (4mg, b.i.d), or placebo in a 26-week double-blind trial. Tissue specific intestinal glucose uptake was measured before and after the treatment period using FDG-PET during euglycemic hyperinsulinemia. In addition, rats were treated with metformin or vehicle for 12weeks, and intestinal FDG uptake was measured in vivo and with autoradiography. Results Glucose uptake increased 2-fold in the small intestine and 3-fold in the colon for the metformin group and associated with improved glycemic control. Rosiglitazone increased only slightly intestinal glucose uptake. In rodents, metformin treatment enhanced intestinal FDG retention (P=0.002), which was localized in the mucosal enterocytes of the small intestine. Conclusions Metformin treatment significantly enhances intestinal glucose uptake from the circulation of patients with type 2 diabetes. This intestine-specific effect is associated with improved glycemic control and localized to mucosal layer. These human findings demonstrate directs effect of metformin on intestinal metabolism and elucidate the actions of metformin. Clinical trial number NCT02526615 © 2017 The Authors
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| 23. |
- Orava, J., et al.
(författare)
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Blunted Metabolic Responses to Cold and Insulin Stimulation in Brown Adipose Tissue of Obese Humans
- 2013
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Ingår i: Obesity. - : Wiley. - 1930-7381. ; 21:11, s. 2279-2287
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Inactive brown adipose tissue (BAT) may predispose to weight gain. This study was designed to measure metabolism in the BAT of obese humans, and to compare it to that in lean subjects. The impact of weight loss on BAT and the association of detectable BAT with various metabolic characteristics were also assessed. Design and Methods: Using positron emission tomography (PET), cold-and insulin-stimulated glucose uptake and blood flow in the BAT of obese and lean humans were quantified. Further, cold-induced glucose uptake was measured in obese subjects before and after a 5-month conventional weight loss. Results: Mean responses in BAT glucose uptake rate to both cold and insulin stimulation were twice as large in lean as in obese subjects. Blood flow in BAT was also lower in obese subjects under cold conditions. The increase in cold-induced BAT glucose uptake rate after weight loss was not statistically significant. Subjects with cold-activated detectable BAT were leaner and had higher whole-body insulin sensitivity than BAT-negative subjects, irrespective of age and gender. Conclusions: The effects of cold and insulin on BAT activity are severely blunted in obesity, and the presence of detectable BAT may contribute to a metabolically healthy status.
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| 24. |
- Rajasilta, O, et al.
(författare)
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Maternal pre-pregnancy BMI associates with neonate local and distal functional connectivity of the left superior frontal gyrus
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 19182-
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Tidskriftsartikel (refereegranskat)abstract
- Maternal obesity/overweight during pregnancy has reached epidemic proportions and has been linked with adverse outcomes for the offspring, including cognitive impairment and increased risk for neuropsychiatric disorders. Prior neuroimaging investigations have reported widespread aberrant functional connectivity and white matter tract abnormalities in neonates born to obese mothers. Here we explored whether maternal pre-pregnancy adiposity is associated with alterations in local neuronal synchrony and distal connectivity in the neonate brain. 21 healthy mother-neonate dyads from uncomplicated pregnancies were included in this study (age at scanning 26.14 ± 6.28 days, 12 male). The neonates were scanned with a 6-min resting-state functional magnetic resonance imaging (rs-fMRI) during natural sleep. Regional homogeneity (ReHo) maps were computed from obtained rs-fMRI data. Multiple regression analysis was performed to assess the association of pre-pregnancy maternal body-mass-index (BMI) and ReHo. Seed-based connectivity analysis with multiple regression was subsequently performed with seed-ROI derived from ReHo analysis. Maternal adiposity measured by pre-pregnancy BMI was positively associated with neonate ReHo values within the left superior frontal gyrus (SFG) (FWE-corrected p < 0.005). Additionally, we found both positive and negative associations (p < 0.05, FWE-corrected) for maternal pre-pregnancy BMI and seed-based connectivity between left SFG and prefrontal, amygdalae, basal ganglia and insular regions. Our results imply that maternal pre-pregnancy BMI associates with local and distal functional connectivity within the neonate left superior frontal gyrus. These findings add to the evidence that increased maternal pre-pregnancy BMI has a programming influence on the developing neonate brain functional networks.
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- Schreya, A, et al.
(författare)
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Functional evaluation of microvascular free flaps with positron emission tomography
- 2006
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Ingår i: Journal of Plastic, reconstructive & Aesthetic Surgery. - : Elsevier BV. - 1748-6815. ; 59:2, s. 158-165
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to assess blood flow (BF) of microvascular free flaps studied with positron emission tomography (PET) in patients with head and neck squamous cell cancer (HNSCC) undergoing major radical surgery 3-4 weeks after high-dose radiotherapy. METHODS: Five patients underwent resection of the HNSCC of the oral cavity followed by microvascular reconstruction with a radial forearm flap. Regional BF in oral and neck tissues was measured with PET using radiolabelled water ([(15)O]H(2)O) twice (1-2 and 12-14 days, respectively) following radical surgery. RESULTS: In the first postoperative PET study, the median BF in the cutaneous flap area was 5.1mL/100g/min, and in the muscle contra-lateral to the recipient site 19.9mL/100g/min. A low flap-to-muscle BF ratio appeared to correlate with circulatory incongruity, and thus with poorer flap success. The follow-up study on the second postoperative week supported the results of the primary PET scan. CONCLUSIONS: This pilot study suggests that PET using [(15)O]H(2)O is a feasible method to quantitatively evaluate BF of the whole free flap in patients operated on for oral HNSCC.
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| 28. |
- Snellman, Anniina, et al.
(författare)
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APOE epsilon 4 gene dose effect on imaging and blood biomarkers of neuroinflammation and beta-amyloid in cognitively unimpaired elderly
- 2023
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Ingår i: Alzheimers Research & Therapy. - 1758-9193. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundNeuroinflammation, characterized by increased reactivity of microglia and astrocytes in the brain, is known to be present at various stages of the Alzheimer's disease (AD) continuum. However, its presence and relationship with amyloid pathology in cognitively normal at-risk individuals is less clear. Here, we used positron emission tomography (PET) and blood biomarker measurements to examine differences in neuroinflammation and beta-amyloid (A beta) and their association in cognitively unimpaired homozygotes, heterozygotes, or non-carriers of the APOE epsilon 4 allele, the strongest genetic risk for sporadic AD.MethodsSixty 60-75-year-old APOE epsilon 4 homozygotes (n = 19), heterozygotes (n = 21), and non-carriers (n = 20) were recruited in collaboration with the local Auria biobank. The participants underwent C-11-PK11195 PET (targeting 18-kDa translocator protein, TSPO), C-11-PiB PET (targeting A beta), brain MRI, and neuropsychological testing including a preclinical cognitive composite (APCC). C-11-PK11195 distribution volume ratios and C-11-PiB standardized uptake value ratios (SUVRs) were calculated for regions typical for early A beta accumulation in AD. Blood samples were drawn for measuring plasma glial fibrillary acidic protein (GFAP) and plasma A beta(1-42/1.40).ResultsIn our cognitively unimpaired sample, cortical C-11-PiB-binding increased according to APOE epsilon 4 gene dose (median composite SUVR 1.47 (range 1.38-1.66) in non-carriers, 1.55 (1.43-2.02) in heterozygotes, and 2.13 (1.61-2.83) in homozygotes, P = 0.002). In contrast, cortical composite C-11-PK11195-binding did not differ between the APOE epsilon 4 gene doses (P = 0.27) or between A beta-positive and A beta-negative individuals (P = 0.81) and associated with higher A beta burden only in APOE epsilon 4 homozygotes (Rho = 0.47, P = 0.043). Plasma GFAP concentration correlated with cortical C-11-PiB (Rho = 0.35, P = 0.040), but not C-11-PK11195-binding (Rho = 0.13, P = 0.47) in A beta-positive individuals. In the total cognitively unimpaired population, both higher composite C-11-PK11195-binding and plasma GFAP were associated with lower hippocampal volume, whereas elevated C-11-PiB-binding was associated with lower APCC scores.ConclusionsOnly A beta burden measured by PET, but not markers of neuroinflammation, differed among cognitively unimpaired elderly with different APOE epsilon 4 gene dose. However, APOE epsilon 4 gene dose seemed to modulate the association between neuroinflammation and A beta.
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