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- Vogel, Jacob W., et al.
(författare)
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Four distinct trajectories of tau deposition identified in Alzheimer’s disease
- 2021
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
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- Gutman, Boris A, et al.
(författare)
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A meta-analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium
- 2022
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Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 352-372
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.
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- Martel-Duguech, Luciana Maria, et al.
(författare)
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ESE audit on management of Adult Growth Hormone Deficiency in clinical practice.
- 2021
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Ingår i: European journal of endocrinology. - 1479-683X. ; 184:2, s. 323-334
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Tidskriftsartikel (refereegranskat)abstract
- Guidelines recommend adults with pituitary disease in whom GH therapy is contemplated, to be tested for GH deficiency (AGHD); however, clinical practice is not uniform.1) To record current practice of AGHD management throughout Europe and benchmark it against guidelines; 2) To evaluate educational status of healthcare professionals about AGHD.On-line survey in endocrine centres throughout Europe.Endocrinologists voluntarily completed an electronic questionnaire regarding AGHD patients diagnosed or treated in 2017-2018.Twenty-eight centres from 17 European countries participated, including 2139 AGHD patients, 28% of childhood-onset GHD. Aetiology was most frequently non-functioning pituitary adenoma (26%), craniopharyngioma (13%) and genetic/congenital mid-line malformations (13%). Diagnosis of GHD was confirmed by a stimulation test in 52% (GHRH+arginine, 45%; insulin-tolerance, 42%, glucagon, 6%; GHRH alone and clonidine tests, 7%); in the remaining, ≥3 pituitary deficiencies and low serum IGF-I were diagnostic. Initial GH dose was lower in older patients, but only women <26 years were prescribed a higher dose than men; dose titration was based on normal serum IGF-I, tolerance and side-effects. In one country, AGHD treatment was not approved. Full public reimbursement was not available in four countries and only in childhood-onset GHD in another. AGHD awareness was low among non-endocrine professionals and healthcare administrators. Postgraduate AGHD curriculum training deserves being improved.Despite guideline recommendations, GH replacement in AGHD is still not available or reimbursed in all European countries. Knowledge among professionals and health administrators needs improvement to optimize care of adults with GHD.
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- Simonelli, L., et al.
(författare)
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The CLEAR X-ray emission spectrometer available at the CLAESS beamline of ALBA synchrotron
- 2023
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Ingår i: Journal of Synchrotron Radiation. - 0909-0495. ; 30, s. 235-241
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Tidskriftsartikel (refereegranskat)abstract
- The CLEAR X-ray emission spectrometer installed at the CLAESS beamline of the ALBA synchrotron is described. It is an energy-dispersive spectrometer based on Rowland circle geometry with 1 m-diameter circle. The energy dispersion is achieved by the combination of a diced analyzer crystal and a unidimensional detector. A single unconventional dynamically bent analyzer crystal (Si 111) permits a wide energy range to be covered, just by exploiting its different reflections (333, 444, 555, 777, 888): 6-22 keV, with a spectrometer efficiency that decreases above 11 keV because of the Si detector thickness (Mythen, 350 μm), while the relative scattering intensities for the Si 333, 444, 555, 777 and 888 reflections correspond to 36, 40, 21, 13 and 15, respectively. The provided energy resolution is typically below 1-2 eV and depends on the beam size, working Bragg angle and reflection exploited. In most cases the energy dispersion ranges from 10 to 20 eV and can be enlarged by working in the out-of-Rowland geometry up to 40 eV. The spectrometer works in full backscattering geometry with the beam passing through the two halves of the analyzer. The vacuum beam path and the particular geometry allow a typical average noise of only 0.5 counts per second per pixel. The spectrometer is mainly used for measuring emission lines and high-resolution absorption spectra, with a typical scanning time for highly concentrated systems of around half an hour, including several repeats. The intrinsic energy dispersion allows systematic collection of resonant X-ray emission maps by measuring high-resolution absorption spectra. Moreover, it allows spectra to be measured on a single-shot basis. Resonant inelastic X-ray scattering experiments to probe electronic excitations are feasible, although the spectrometer is not optimized for this purpose due to the limited energy resolution and scattering geometry provided. In that case, to minimize the quasi-elastic line, the spectrometer is able to rotate along the beam path. Advantages and disadvantages with respect to other existing spectrometers are highlighted.
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