المؤلفون: Erik Rein‐Hedin, Folke Sjöberg, Cecilia Ganslandt, Johan Skoog, Helene Zachrisson, Thomas Bengtsson, Carl‐Johan Dalsgaard

المصدر: Clinical and Translational Science, Vol 17, Iss 2, Pp n/a-n/a (2024)

مصطلحات موضوعية: Therapeutics. Pharmacology, RM1-950, Public aspects of medicine, RA1-1270

الوصف: Abstract Buloxibutid (also known as C21) is a potent and selective angiotensin II type 2 receptor (AT2R) agonist, in development for oral treatment of fibrotic lung disease. This phase I, open‐label, pharmacodynamic study investigated vascular effects of buloxibutid in five healthy male volunteers. Subjects were administered intra‐arterial infusions of buloxibutid for 5 min in ascending doses of 3, 10, 30, 100, and 200 μg/min, infused sequentially in the forearm. Infusions of sodium nitroprusside (SNP) solution in doses of 0.8–3.2 μg/min were administered as a positive control. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Safety and tolerability of intra‐arterial administrations of buloxibutid were evaluated. Following infusion of buloxibutid in doses of 3–200 μg/min, the range of increase in FBF was 27.8%, 17.2%, 37.0%, 28.5%, and 60.5%, compared to the respective baseline. The largest increase was observed in the highest dose group. Infusions of SNP as a positive control, increased FBF 230–320% compared to baseline. Three adverse events (AEs) of mild intensity, not related to buloxibutid or SNP, were reported for two subjects. Two of these AEs were related to study procedures. There were no clinically relevant changes in arterial blood pressure during the study period. Intra‐arterial infusion of buloxibutid in low, ascending doses increased FBF, indicating that buloxibutid may be effective in conditions associated with endothelial dysfunction. Venous occlusion plethysmography was found to be a useful method to explore pharmacodynamic vascular effects of novel AT2R agonists, while avoiding systemic adverse effects.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1752-8054Test; https://doaj.org/toc/1752-8062Test

الوصول الحر: https://doaj.org/article/55ff203de6964d7b9a14d27c9990b251Test

المؤلفون: Atef Badji, Joana Pereira, Sara Shams, Johan Skoog, Anna Marseglia, Konstantinos Poulakis, lina Ryden, Kaj Blennow, Henrik Zetterberg, Silke Kern, Anna Wahlund, Lars-Olof Wahlund, Hélène Girouard, Ingmar Skoog, Eric Westman

المصدر: Cerebral Circulation - Cognition and Behavior, Vol 6, Iss , Pp 100048- (2024)

مصطلحات موضوعية: Specialties of internal medicine, RC581-951, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2666245022000137Test; https://doaj.org/toc/2666-2450Test

الوصول الحر: https://doaj.org/article/a756af7b1a0a42d19dd41ffbf9d2ed69Test

المؤلفون: Anna Marseglia, Alexander Darin-Mattsson, Johan Skoog, Lina Rydén, Timothy Hadarsson-Bodin, Silke Kern, Therese Rydberg Sterner, Ying Shang, Anna Zettergren, Eric Westman, Ingmar Skoog

المصدر: Cerebral Circulation - Cognition and Behavior, Vol 6, Iss , Pp 100095- (2024)

مصطلحات موضوعية: Specialties of internal medicine, RC581-951, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2666245022000605Test; https://doaj.org/toc/2666-2450Test

الوصول الحر: https://doaj.org/article/3f48026d8a5642ef90683e8f3086fb4aTest

المؤلفون: Jenna Najar, Valgeir Thorvaldsson, Silke Kern, Johan Skoog, Margda Waern, Henrik Zetterberg, Kaj Blennow, Ingmar Skoog, Anna Zettergren

المصدر: Neurobiology of Disease, Vol 189, Iss , Pp 106357- (2023)

مصطلحات موضوعية: Cognition, Polygenic risk scores, Cognitive decline, APOE genotype, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: Background: Polygenic risk scores for Alzheimer's disease (AD-PRSs) have been associated with cognition. However, few studies have examined the effect of AD-PRS beyond the APOE gene, and the influence of genetic variants related to level of cognitive ability (COG-PRS) on cognitive performance over time in the general older population. Method: A population-based sample of 965 individuals born in 1930, with genetic and standardized cognitive data on six psychometric tests (Thurstone's picture memory, immediate recall of 10 words, Block design, word fluency, figure identification, delayed recall of 12 items), were examined at age 70, 75, 79, and 85 years. Non-APOE AD-PRSs and COG-PRSs (P

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S096999612300373XTest; https://doaj.org/toc/1095-953XTest

الوصول الحر: https://doaj.org/article/1d6f3371074c4d0896cd0e15861ae4d1Test

المؤلفون: Lina Rydén, Hanna Wetterberg, Felicia Ahlner, Hanna Falk Erhag, Pia Gudmundsson, Xinxin Guo, Erik Joas, Lena Johansson, Silke Kern, Madeleine Mellqvist Fässberg, Jenna Najar, Mats Ribbe, Therese Rydberg Sterner, Simona Sacuiu, Jessica Samuelsson, Robert Sigström, Johan Skoog, Margda Waern, Anna Zettergren, Ingmar Skoog

المصدر: Frontiers in Epidemiology, Vol 3 (2023)

مصطلحات موضوعية: attrition, population studies, drop out, epidemiogy, representativeness, Infectious and parasitic diseases, RC109-216

الوصف: BackgroundLongitudinal studies are essential to understand the ageing process, and risk factors and consequences for disorders, but attrition may cause selection bias and impact generalizability. We describe the 1930 cohort of the Gothenburg H70 Birth Cohort Studies, followed from age 70 to 88, and compare baseline characteristics for those who continue participation with those who die, refuse, and drop out for any reason during follow-up.MethodsA population-based sample born 1930 was examined with comprehensive assessments at age 70 (N = 524). The sample was followed up and extended to increase sample size at age 75 (N = 767). Subsequent follow-ups were conducted at ages 79, 85, and 88. Logistic regression was used to analyze baseline characteristics in relation to participation status at follow-up.ResultsRefusal to participate in subsequent examinations was related to lower educational level, higher blood pressure, and lower scores on cognitive tests. Both attrition due to death and total attrition were associated with male sex, lower educational level, smoking, ADL dependency, several diseases, poorer lung function, slower gait speed, lower scores on cognitive tests, depressive symptoms, and a larger number of medications. Attrition due to death was also associated with not having a partner.ConclusionsIt is important to consider different types of attrition when interpreting results from longitudinal studies, as representativeness and results may be differently affected by different types of attrition. Besides reducing barriers to participation, methods such as imputation and weighted analyses can be used to handle selection bias.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fepid.2023.1151519/fullTest; https://doaj.org/toc/2674-1199Test

الوصول الحر: https://doaj.org/article/40050c54d5284354a27a541d10178b09Test

المؤلفون: Margda Waern, Ingmar Skoog, Lena Johansson, Xinxin Guo, Silke Kern, Erik Joas, Hanna Wetterberg, Lina Rydén, Felicia Ahlner, Hanna Falk Erhag, Pia Gudmundsson, Madeleine Mellqvist Fässberg, Jenna Najar, Mats Ribbe, Therese Rydberg Sterner, Jessica Samuelsson, Simona Sacuiu, Robert Sigström, Johan Skoog, Anna Zettergren

المصدر: BMJ Open, Vol 12, Iss 12 (2022)

مصطلحات موضوعية: Medicine

الوصف: Objectives To describe representativeness in the Gothenburg H70 1930 Birth Cohort Study.Design Repeated cross-sectional examinations of a population-based study.Setting Gothenburg, Sweden.Participants All residents of Gothenburg, Sweden, born on specific birth dates in 1930 were invited to a comprehensive health examination at ages 70, 75, 79, 85 and 88. The number of participants at each examination was 524 at age 70, 767 at age 75, 580 at age 79, 416 at age 85, and 258 at age 88.Primary outcome measures We compared register data on sociodemographic characteristics and hospital discharge diagnoses between participants and (1) refusals, (2) all same-aged individuals in Gothenburg and (3) all same-aged individuals in Sweden. We also compared mortality rates between participants and refusals.Results Refusal rate increased with age. At two or more examination waves, participants compared with refusals had higher educational level, more often had osteoarthritis, had lower mortality rates, had lower prevalence of neuropsychiatric, alcohol-related and cardiovascular disorders, and were more often married. At two examination waves, participants compared with same-aged individuals in Gothenburg had higher education and were more often born in Sweden. At two examination waves or more, participants compared with same-aged individuals in Sweden had higher education, had higher average income, less often had ischaemic heart disease, were less often born in Sweden and were more often divorced.Conclusions Participants were more similar to the target population in Gothenburg than to refusals and same-aged individuals in Sweden. Our study shows the importance of having different comparison groups when assessing representativeness of population studies, which is important in evaluating generalisability of results. The study also contributes unique and up-to-date knowledge about participation bias in these high age groups.

وصف الملف: electronic resource

العلاقة: https://bmjopen.bmj.com/content/12/12/e068165.fullTest; https://doaj.org/toc/2044-6055Test

الوصول الحر: https://doaj.org/article/7aa59fdf86ed4f86aaecc6a5c616e5d1Test

المؤلفون: Fredrik Öhman, David Berron, Kathryn V. Papp, Silke Kern, Johan Skoog, Timothy Hadarsson Bodin, Anna Zettergren, Ingmar Skoog, Michael Schöll

المصدر: Frontiers in Digital Health, Vol 4 (2022)

مصطلحات موضوعية: Alzheimers disease (AD), digital cognitive assessment, smartphone-based cognitive assessments, remote and unsupervised assessment, episodic memory, Medicine, Public aspects of medicine, RA1-1270, Electronic computers. Computer science, QA75.5-76.95

الوصف: BackgroundMobile app-based tools have the potential to yield rapid, cost-effective, and sensitive measures for detecting dementia-related cognitive impairment in clinical and research settings. At the same time, there is a substantial need to validate these tools in real-life settings. The primary aim of this study was thus to evaluate the feasibility, validity, and reliability of mobile app-based tasks for assessing cognitive function in a population-based sample of older adults.MethodA total of 172 non-demented (Clinical Dementia Rating 0 and 0.5) older participants (aged 76–77) completed two mobile app-based memory tasks—the Mnemonic Discrimination Task for Objects and Scenes (MDT-OS) and the long-term (24 h) delayed Object-In-Room Recall Task (ORR-LDR). To determine the validity of the tasks for measuring relevant cognitive functions in this population, we assessed relationships with conventional cognitive tests. In addition, psychometric properties, including test-retest reliability, and the participants’ self-rated experience with mobile app-based cognitive tasks were assessed.ResultMDT-OS and ORR-LDR were weakly-to-moderately correlated with the Preclinical Alzheimer's Cognitive Composite (PACC5) (r = 0.3–0.44, p

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fdgth.2022.933265/fullTest; https://doaj.org/toc/2673-253XTest

الوصول الحر: https://doaj.org/article/d09e616fa94f4fa2b32129ea88645f26Test

المؤلفون: Atef Badji, Joana B. Pereira, Sara Shams, Johan Skoog, Anna Marseglia, Konstantinos Poulakis, Lina Rydén, Kaj Blennow, Henrik Zetterberg, Silke Kern, Anna Zettergren, Lars-Olof Wahlund, Hélène Girouard, Ingmar Skoog, Eric Westman

المصدر: Frontiers in Aging Neuroscience, Vol 13 (2022)

مصطلحات موضوعية: CSF (cerebrospinal fluid), hypertension, brain, MRI, white matter, aging, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: Background: Hypertension is an important risk factor for Alzheimer’s disease (AD). The pathophysiological mechanisms underlying the relationship between AD and hypertension are not fully understood, but they most likely involve microvascular dysfunction and cerebrovascular pathology. Although previous studies have assessed the impact of hypertension on different markers of brain integrity, no study has yet provided a comprehensive comparison of cerebrospinal fluid (CSF) biomarkers and structural brain differences between normotensive and hypertensive groups in a single and large cohort of older adults in relationship to cognitive performances.Objective: The aim of the present work was to investigate the differences in cognitive performances, CSF biomarkers and magnetic resonance imaging (MRI) of brain structure between normotensive, controlled hypertensive, uncontrolled hypertensive, and untreated hypertensive older adults from the Gothenburg H70 Birth Cohort Studies.Methods: As an indicator of vascular brain pathology, we measured white matter hyperintensities (WMHs), lacunes, cerebral microbleeds, enlarged perivascular space (epvs), and fractional anisotropy (FA). To assess markers of AD pathology/neurodegeneration, we measured hippocampal volume, temporal cortical thickness on MRI, and amyloid-β42, phosphorylated tau, and neurofilament light protein (NfL) in cerebrospinal fluid. Various neuropsychological tests were used to assess performances in memory, attention/processing speed, executive function, verbal fluency, and visuospatial abilities.Results: We found more white matter pathology in hypertensive compared to normotensive participants, with the highest vascular burden in uncontrolled participants (e.g., lower FA, more WMHs, and epvs). No significant difference was found in any MRI or CSF markers of AD pathology/neurodegeneration when comparing normotensive and hypertensive participants, nor among hypertensive groups. No significant difference was found in most cognitive functions between groups.Conclusion: Our results suggest that good blood pressure control may help prevent cerebrovascular pathology. In addition, hypertension may contribute to cognitive decline through its effect on cerebrovascular pathology rather than AD-related pathology. These findings suggest that hypertension is associated with MRI markers of vascular pathology in the absence of a significant decline in cognitive functions.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fnagi.2021.777475/fullTest; https://doaj.org/toc/1663-4365Test

الوصول الحر: https://doaj.org/article/52ea82fe5fce4b56af5c959aa2c80203Test

المؤلفون: Johan Skoog, Christina Svensson, Per Eriksson, Christopher Sjöwall, Helene Zachrisson

المصدر: Frontiers in Medicine, Vol 8 (2022)

مصطلحات موضوعية: giant cell (temporal) arteritis, color duplex ultrasound, large vessel vasculitis, diagnostic imaging, IMT (intimal medial thickness), Medicine (General), R5-920

الوصف: ObjectiveTo evaluate the diagnostic performance of an extended ultrasound protocol in patients referred under the suspicion of giant cell arteritis (GCA).MethodsConsecutive patients with suspected GCA were examined with an extended color duplex ultrasound (CDU) protocol during a period of 2 years. The extended CDU protocol included temporal, axillary, subclavian, brachiocephalic, and carotid arteries. The reference was clinically diagnosed GCA, confirmed after ≥6-month follow-up. Hypo- or medium-echogenic, circumferential, homogenous wall thickening, and/or a positive compression sign in temporal arteries, were regarded as typical signs of arteritis.ResultsOf the eligible 201 patients, 83 (41%) received a clinical GCA diagnosis at follow-up ≥6 months post CDU examination. Among these cases, 48 (58%) demonstrated inflammation solely in temporal arteries, 8 (10%) showed abnormalities restricted to extra-cranial vessels, and 23 (28%) patients displayed inflammatory changes in both temporal and extra-cranial arteries. Color duplex ultrasound of temporal arteries yielded a diagnostic sensitivity and specificity [95% confidence intervals (CI)] of 86% (76–92%) and 99% (95–99%), respectively. By adding axillary artery examination, the sensitivity increased to 92% (83–97%) while the specificity remained unchanged. Further, inclusion of subclavian artery marginally increased the sensitivity by 1%. Finally, by also including brachiocephalic and common carotid arteries resulted in a sensitivity of 95% (88–99%) and a specificity of 98% (94–99%).ConclusionsColor duplex ultrasound examination demonstrated a high accuracy in diagnosing patients both with cranial and extra-cranial GCA. Further examination of brachiocephalic and common carotid arteries can increase the sensitivity without affecting the specificity when temporal and axillary findings are indecisive. Finally, the extended CDU protocol allows measurement of the general burden of inflammation, which could be relevant for future monitoring purposes.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmed.2021.807996/fullTest; https://doaj.org/toc/2296-858XTest

الوصول الحر: https://doaj.org/article/114e89b7f504400d868b4d78673e24b3Test

المؤلفون: Moa Bydén, Anna Segernäs, Hans Thulesius, Farkas Vanky, Eva Ahlgren, Johan Skoog, Helene Zachrisson

المصدر: Frontiers in Surgery, Vol 8 (2021)

مصطلحات موضوعية: delirium, cerebrovascular reactivity, transcranial Doppler, cardiopulmonary bypass, mini mental state examination, A Quick Test of cognitive speed, Surgery, RD1-811

الوصف: Introduction: Postoperative delirium is a common complication after cardiac surgery with cardiopulmonary bypass (CPB). Compromised regulation of the cerebral circulation may be a predisposing factor for delirium. However, the potential relationship between cerebrovascular reserve capacity and delirium is unknown. The aim of this study was to investigate if impaired cerebrovascular reserve capacity was associated with postoperative delirium.Methods: Forty-two patients scheduled for cardiac surgery with CPB were recruited consecutively. All patients underwent preoperative transcranial Doppler (TCD) ultrasound with calculation of breath-hold index (BHI). BHI < 0.69 indicated impaired cerebrovascular reserve capacity. In addition, patients were examined with preoperative neuropsychological tests such as MMSE (Mini Mental State Examination) and AQT (A Quick Test of cognitive speed). Postoperative delirium was assessed using Nursing Delirium Screening Scale (Nu-DESC) in which a score of ≥2 was considered as delirium.Results: Six patients (14%) scored high for postoperative delirium and all demonstrated impaired preoperative cerebrovascular reserve capacity. Median (25th−75th percentile) BHI in patients with postoperative delirium was significantly lower compared to the non-delirium group [0.26 (−0.08–0.44) vs. 0.83 (0.57–1.08), p = 0.002]. Preoperative MMSE score was lower in patients who developed postoperative delirium (median, 25th−75th percentile; 26.5, 24–28 vs. 28.5, 27–29, p = 0.024). Similarly, patients with postoperative delirium also displayed a slower performance during the preoperative cognitive speed test AQT color and form (mean ± SD; 85.8 s ± 19.3 vs. 69.6 s ± 15.8, p = 0.043).Conclusion: The present findings suggest that an extended preoperative ultrasound protocol with TCD evaluation of cerebrovascular reserve capacity and neuropsychological tests may be valuable in identifying patients with increased risk of developing delirium after cardiac surgery.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fsurg.2021.658849/fullTest; https://doaj.org/toc/2296-875XTest

الوصول الحر: https://doaj.org/article/92afe583269c44a58b02bf62e45df5c3Test