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Este trabajo analiza el deterioro del Estado de Derecho en Polonia desde las elecciones de 2015, en las que el partido ultraconservador Ley y Justicia consiguió la mayoría legislativa y accedió al Gobierno. Desde entonces, esta situación le ha permitido llevar a cabo modificaciones legislativas que han acabado afectando a la independencia judicial en el país. Entre otros factores, la modificación de la composición del Tribunal Constitucional y el Tribunal Supremo o la politización del Consejo Nacional del Poder Judicial, órgano constitucional encargado de los nombramientos judiciales, han contribuido al deterioro del Estado de Derecho en Polonia. Ante esta situación, comienza a producirse una reacción en forma de diálogo entre el TJUE y el TEDH, de forma que ambos Tribunales se aluden mutuamente a través de sus sentencias y desarrollan el concepto de «tribunal establecido por ley». Como resultado de dicha interacción, se amplía el contenido del derecho a un tribunal establecido por la ley y se establece que las irregularidades producidas en el procedimiento de nombramiento de los jueces pueden provocar el menoscabo de aquel derecho. Se acaba incluyendo así la legalidad del procedimiento de nombramiento de los jueces al contenido del derecho a un tribunal establecido por la ley. Recibido: 25 octubre 2022Aceptado: 22 febrero 2023

El presente trabajo presenta uno de los nuevos fondos aprobados por la Unión Europea para hacer frente a las consecuencias socioeconómicas negativas derivadas de la pandemia del COVID-19 en los Estados miembros, el Instrumento de Recuperación de la Unión Europea Next Generation EU, así como uno de los programas que lo componen, el Mecanismo de Recuperación y Resiliencia. Asimismo, se estudia con detalle la legislación aprobada en España para la recepción de estos fondos y su repercusión sobre el régimen jurídico de las subvenciones públicas financiables con fondos europeos.

The study of sex differences in Alzheimer’s disease is increasingly recognized as a key priority in research and clinical development. People with Down syndrome represent the largest population with a genetic link to Alzheimer’s disease (>90% in the 7th decade). Yet, sex differences in Alzheimer’s disease manifestations have not been fully investigated in these individuals, who are key candidates for preventive clinical trials. In this double-centre, cross-sectional study of 628 adults with Down syndrome [46% female, 44.4 (34.6; 50.7) years], we compared Alzheimer’s disease prevalence, as well as cognitive outcomes and AT(N) biomarkers across age and sex. Participants were recruited from a population-based health plan in Barcelona, Spain, and from a convenience sample recruited via services for people with intellectual disabilities in England and Scotland. They underwent assessment with the Cambridge Cognitive Examination for Older Adults with Down Syndrome, modified cued recall test and determinations of brain amyloidosis (CSF amyloid-β 42 / 40 and amyloid-PET), tau pathology (CSF and plasma phosphorylated-tau181) and neurodegeneration biomarkers (CSF and plasma neurofilament light, total-tau, fluorodeoxyglucose-PET and MRI). We used within-group locally estimated scatterplot smoothing models to compare the trajectory of biomarker changes with age in females versus males, as well as by apolipoprotein ɛ4 carriership. Our work revealed similar prevalence, age at diagnosis and Cambridge Cognitive Examination for Older Adults with Down Syndrome scores by sex, but males showed lower modified cued recall test scores from age 45 compared with females. AT(N) biomarkers were comparable in males and females. When considering apolipoprotein ɛ4, female ɛ4 carriers showed a 3-year earlier age at diagnosis compared with female non-carriers (50.5 versus 53.2 years, P = 0.01). This difference was not seen in males (52.2 versus 52.5 years, P = 0.76). Our exploratory analyses considering sex, apolipoprotein ɛ4 and biomarkers showed that female ɛ4 carriers tended to exhibit lower CSF amyloid-β 42/amyloid-β 40 ratios and lower hippocampal volume compared with females without this allele, in line with the clinical difference. This work showed that biological sex did not influence clinical and biomarker profiles of Alzheimer’s disease in adults with Down syndrome. Consideration of apolipoprotein ɛ4 haplotype, particularly in females, may be important for clinical research and clinical trials that consider this population. Accounting for, reporting and publishing sex-stratified data, even when no sex differences are found, is central to helping advance precision medicine.

Introduction: We assessed the influence of education as a proxy of cognitive reserve and age on the dementia with Lewy bodies (DLB) metabolic pattern. Methods: Brain 18F-fluorodeoxyglucose positron emission tomography and clinical/demographic information were available in 169 probable DLB patients included in the European DLB-consortium database. Principal component analysis identified brain regions relevant to local data variance. A linear regression model was applied to generate age- and education-sensitive maps corrected for Mini-Mental State Examination score, sex (and either education or age). Results: Age negatively covaried with metabolism in bilateral middle and superior frontal cortex, anterior and posterior cingulate, reducing the expression of the DLB-typical cingulate island sign (CIS). Education negatively covaried with metabolism in the left inferior parietal cortex and precuneus (making the CIS more prominent). Discussion: These findings point out the importance of tailoring interpretation of DLB biomarkers considering the concomitant effect of individual, non-disease-related variables such as age and cognitive reserve.

Striatal dopamine transporter (DAT) uptake assessment through I-123-Ioflupane Single-Pphoton Emission Computed Tomography (SPECT) provides valuable information about the dopaminergic denervation occurring in Parkinson's disease (PD). However, little is known about the clinical or biological relevance of extrastriatal DAT uptake in PD. Here, from the Parkinson's Progression Markers Initiative, we studied 623 participants (431 PD and 192 healthy controls) with available SPECT data. Even though striatal denervation was undoubtedly the imaging hallmark of PD, extrastriatal DAT uptake was also reduced in patients with PD. Topographically, widespread frontal but also temporal and posterior cortical regions showed lower DAT uptake in PD patients with respect to healthy controls. Importantly, a longitudinal voxelwise analysis confirmed an active one-year loss of extrastriatal DAT uptake within the PD group. Extrastriatal DAT uptake also correlated with the severity of motor symptoms, cognitive performance, and cerebrospinal fluid alpha-synuclein levels. In addition, we found an association between the Catechol-O-methyltransferase val158met genotype and extrastriatal DAT uptake. These results highlight the clinical and biological relevance of extrastriatal SPECT-DAT uptake in PD. (C) 2020 Elsevier Inc. All rights reserved.

Background Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by I-123-Ioflupane brain single-photon emission computed tomography of dopamine transporter and F-18-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood. Objective We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies. Methods We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest-based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls. Results There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism. Conclusions Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. Funding Agencies|Velox Foundation [project 1123]; Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung [SNF 320030_169876]

Purpose The purpose of this study is to develop and validate a 3D deep learning model that predicts the final clinical diagnosis of Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), mild cognitive impairment due to Alzheimer’s disease (MCI-AD), and cognitively normal (CN) using fluorine 18 fluorodeoxyglucose PET (18F-FDG PET) and compare model’s performance to that of multiple expert nuclear medicine physicians’ readers. Materials and methods Retrospective 18F-FDG PET scans for AD, MCI-AD, and CN were collected from Alzheimer’s disease neuroimaging initiative (556 patients from 2005 to 2020), and CN and DLB cases were from European DLB Consortium (201 patients from 2005 to 2018). The introduced 3D convolutional neural network was trained using 90% of the data and externally tested using 10% as well as comparison to human readers on the same independent test set. The model’s performance was analyzed with sensitivity, specificity, precision, F1 score, receiver operating characteristic (ROC). The regional metabolic changes driving classification were visualized using uniform manifold approximation and projection (UMAP) and network attention. Results The proposed model achieved area under the ROC curve of 96.2% (95% confidence interval: 90.6–100) on predicting the final diagnosis of DLB in the independent test set, 96.4% (92.7–100) in AD, 71.4% (51.6–91.2) in MCI-AD, and 94.7% (90–99.5) in CN, which in ROC space outperformed human readers performance. The network attention depicted the posterior cingulate cortex is important for each neurodegenerative disease, and the UMAP visualization of the extracted features by the proposed model demonstrates the reality of development of the given disorders. Conclusion Using only 18F-FDG PET of the brain, a 3D deep learning model could predict the final diagnosis of the most common neurodegenerative disorders which achieved a competitive performance compared to the human readers as well as their consensus.

Although there is evidence that chemotherapy can have side effects on metabolism and brain function, there are few studies on the occurrence of these side effects with immunotherapy. The present study was conducted to assess whether brain metabolic changes occur in patients with malignant melanoma under immunotherapy. Thirty-nine patients after surgical intervention and with a diagnosis of malignant melanoma were retrospectively included and were divided into two groups: one group under the first-line therapy with anti-programmed cell death-1 +/- anti-cytotoxic T lymphocyte antigen-4 monoclonal antibodies and the other group without any treatment after surgery, which served as a control. Basal and follow-up whole body and brain 2-[F-18]fluoro-2-deoxy-D-glucose (F-18]FDG) PET/computed tomography (CT) studies were performed. Changes in brain glucose metabolism after treatment initiation of the immunotherapy group were compared with the findings in the control group. In addition, longitudinal regression analysis to investigate whether the time under immunotherapy influenced the changes of brain metabolism was performed. None of the patients presented cognitive impairment or other neurological alterations between basal and follow-up brain [F-18]FDG PET/CT examinations. The statistical analysis revealed a significant relative SUV (SUVr)-loss in the left frontal region in patients of the immunotherapy group compared with the control group, with r(adjusted) = -0.62 and P = 0.008. Severity of SUVr-loss was correlated with duration of treatment. Patients with disseminated malignant melanoma receiving immunotherapy may present a decrease of brain metabolism in the left frontal region, which is related with time-under-treatment, without any clinical evidence of neurological disorder.

Plasma tau phosphorylated at threonine 181 (p-tau181) predicts Alzheimer’s disease (AD) pathology with high accuracy in the general population. In this study, we investigated plasma p-tau181 as a biomarker of AD in individuals with Down syndrome (DS). We included 366 adults with DS (240 asymptomatic, 43 prodromal AD, 83 AD dementia) and 44 euploid cognitively normal controls. We measured plasma p-tau181 with a Single molecule array (Simoa) assay. We examined the diagnostic performance of p-tau181 for the detection of AD and the relationship with other fluid and imaging biomarkers. Plasma p-tau181 concentration showed an area under the curve of 0.80 [95% CI 0.73–0.87] and 0.92 [95% CI 0.89–0.95] for the discrimination between asymptomatic individuals versus those in the prodromal and dementia groups, respectively. Plasma p-tau181 correlated with atrophy and hypometabolism in temporoparietal regions. Our findings indicate that plasma p-tau181 concentration can be useful to detect AD in DS., Plasma tau phosphorylated at threonine 181 (p-tau181) predicts Alzheimer’s disease (AD) pathology. Here, the authors investigated whether plasma ptau181 could be a potential biomarker of AD in individuals with Down syndrome (DS) and find plasma p-tau181 can detect AD in DS adults.

Introduction Bilingualism exerts neuroprotective effects against neurodegeneration. In Huntington's disease (HD), the systems involved in bilingual control show early compromise, but the effect of bilingualism on the course of HD is unknown. Methods We addressed the impact of livelong use of bilingualism on the clinical features, brain structure and function in 30 early-mild stage HD patients. Using voxel-wise regression analysis, we explored the effect of levels of use of bilingualism on grey-matter volume (GMV) and 18F-FDG metabolism. Results Higher use of bilingualism was associated with better performance in inhibitory control and set-shifting independently of age and education and with higher GMV in the inferior frontal gyrus. 18F-FDG data revealed a significant effect on multiple fronto-temporal regions, specifically, in the dorsal anterior cingulate cortex, the anterior insula, the ventromedial orbital prefrontal cortex and the inferior frontal gyrus. These changes contributed to better inhibitory control and set-shifting and to more preserved motor and functional capacity. Conclusion In HD, lifelong use of bilingualism is associated with structural and metabolic brain changes that have an impact on cognition, movement and functionality. These findings highlight the importance of stimulating cognitive and brain reserve in HD and in other neurodegenerative conditions.

Objective Normalization to an appropriate reference region in F-18-FDG PET imaging may enhance diagnostic performance in Huntington disease (HD). We aimed to identify stable brain areas that could be used to model neurometabolic degeneration in HD correlating imaging (SUVr(values) at the basal ganglia [BBGG]) and clinical parameters (disease burden score [DBS]). Materials and Methods We performed brain F-18-FDG PET/CT in 38 manifest HD patients (mean(age) +/- SD, 54 +/- 14.3 years; CAG(repeats) +/- SD, 44.2 +/- 3.1), 20 premanifest HD patients (mean(age) +/- SD, 42.7 +/- 11.7 years; CAG(repeats) +/- SD, 40 +/- 3.8), and 18 healthy controls (NC; mean(age) +/- SD, 45 +/- 13.2 years). For quantitative analysis, we selected (a) defined reference regions from the Montreal Neurological Institute space atlas (pons, whole cerebellum, cerebral white matter, thalamus, and a pons-cerebellar vermis region of interest), and (b) reference clusters obtained by voxelwise statistical comparison across groups (P < 0.05 FWE; extent voxel threshold k = 200). Each candidate reference region and reference cluster was quantitatively assessed using imaging and clinical parameters. Results Comparing HD and NC groups, we obtained a reference cluster in the cerebellum, and in temporal and frontal lobes. Comparing manifest HD and premanifest HD patients, we observed reference clusters in the cerebellum, pons, thalamus, parietal lobe, and cuneus. The set of reference regions showed a significant correlation between SUVr(values) at the BBGG and DBS in all HD patients. In premanifest HD patients, the correlation between SUVr(values) at the BBGG and DBS was significant using the pons-cerebellar vermis region of interest, the thalamus as defined reference regions, and the pons and thalamus as reference clusters. In manifest HD patients, the correlation was significant using the temporal and white matter frontal lobe clusters. Variance between SUVr(values) in the set of reference regions and reference clusters was minimal within NC. Conclusions The pons may be a stable and reliable region to calculate SUVr(values) to model the neurometabolic degeneration in quantitative F-18-FDG PET imaging in HD.

Background The mechanisms through which kappa opioid receptor (KOR) agonists induce psychotomimetic effects are largely unknown, although the modulation of this receptor has attracted attention for its clinical use. In this work, we characterize the neuropharmacological effects of salvinorin-A, a highly selective KOR agonist. Methods Changes in multimodal electroencephalography, single-photon emission computed tomography, and subjective effects following the acute administration of salvinorin-A are reported. The study included 2 sub-studies that employed a double-blind, crossover, randomized, placebo-controlled design. Results The electroencephalography measures showed a marked increase in delta and gamma waves and a decrease in alpha waves while subjects were under the effect of salvinorin-A. Regarding single-photon emission computed tomography measures, significant decreases in regional cerebral blood flow were detected in multiple regions of the frontal, temporal, parietal, and occipital cortices. Significant regional cerebral blood flow increases were observed in some regions of the medial temporal lobe, including the amygdala, the hippocampal gyrus, and the cerebellum. The pattern of subjective effects induced by salvinorin-A was similar to those observed in relation to other psychotomimetic drugs but with an evidently dissociative nature. No dysphoric effects were reported. Conclusion The salvinorin-A–mediated KOR agonism induced dramatic psychotomimetic effects along with a generalized decrease in cerebral blood flow and electric activity within the cerebral cortex.

Introduction Positron emission tomography (PET) amyloid quantification methods require magnetic resonance imaging (MRI) for spatial registration and a priori reference region to scale the images. Furthermore, different tracers have distinct thresholds for positivity. We propose the AMYQ index, a new measure of amyloid burden, to overcome these limitations. Methods We selected 18F-amyloid scans from ADNI and Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL) with the corresponding T1-MRI. A subset also had neuropathological data. PET images were normalized, and the AMYQ was calculated based on an adaptive template. We compared AMYQ with the Centiloid scale on clinical and neuropathological diagnostic performance. Results AMYQ was related with amyloid neuropathological burden and had excellent diagnostic performance to discriminate controls from patients with Alzheimer's disease (AD) (area under the curve [AUC] = 0.86). AMYQ had a high agreement with the Centiloid scale (intraclass correlation coefficient [ICC] = 0.88) and AUC between 0.94 and 0.99 to discriminate PET positivity when using different Centiloid cutoffs. Discussion AMYQ is a new MRI-independent index for standardizing and quantifying amyloid load across tracers.

This cohort study examines Alzheimer disease symptoms and age at onset; changes in amyloid, tau, and neurodegeneration biomarkers; and topography of brain changes in adults with Down syndrome., Key Points Question What is the association of the apolipoprotein E (APOE) ɛ4 allele with Alzheimer disease–related clinical and biomarker changes in Down syndrome? Findings In this cohort study of 464 adults with Down syndrome, carriers of the APOE ɛ4 allele showed both earlier clinical symptoms of Alzheimer disease and earlier changes in amyloid (cerebrospinal fluid Aβ1-42/1-40 and amyloid positron emission tomography), tau (plasma phosphorylated tau 181), and neurodegeneration (cerebral glucose hypometabolism and hippocampal atrophy) biomarkers. The APOE ɛ4 allele also altered the topography of neurodegeneration. Meaning Results of this study suggest that the APOE ɛ4 allele can modulate both the clinical expression and the biomarkers of Alzheimer disease in a genetic form of the disease, such as in Down syndrome., Importance Alzheimer disease (AD) is the leading cause of death in individuals with Down syndrome (DS). Previous studies have suggested that the APOE ɛ4 allele plays a role in the risk and age at onset of dementia in DS; however, data on in vivo biomarkers remain scarce. Objective To investigate the association of the APOE ɛ4 allele with clinical and multimodal biomarkers of AD in adults with DS. Design, Setting, and Participants This dual-center cohort study recruited adults with DS in Barcelona, Spain, and in Cambridge, UK, between June 1, 2009, and February 28, 2020. Included individuals had been genotyped for APOE and had at least 1 clinical or AD biomarker measurement; 2 individuals were excluded because of the absence of trisomy 21. Participants were either APOE ɛ4 allele carriers or noncarriers. Main Outcomes and Measures Participants underwent a neurological and neuropsychological assessment. A subset of participants had biomarker measurements: Aβ1-42, Aβ1-40, phosphorylated tau 181 (pTau181) and neurofilament light chain (NfL) in cerebrospinal fluid (CSF), pTau181, and NfL in plasma; amyloid positron emission tomography (PET); fluorine 18–labeled-fluorodeoxyglucose PET; and/or magnetic resonance imaging. Age at symptom onset was compared between APOE ɛ4 allele carriers and noncarriers, and within-group local regression models were used to compare the association of biomarkers with age. Voxelwise analyses were performed to assess topographical differences in gray matter metabolism and volume. Results Of the 464 adults with DS included in the study, 97 (20.9%) were APOE ɛ4 allele carriers and 367 (79.1%) were noncarriers. No differences between the 2 groups were found by age (median [interquartile range], 45.9 [36.4-50.2] years vs 43.7 [34.9-50.2] years; P = .56) or sex (51 male carriers [52.6%] vs 199 male noncarriers [54.2%]). APOE ɛ4 allele carriers compared with noncarriers presented with AD symptoms at a younger age (mean [SD] age, 50.7 [4.4] years vs 52.7 [5.8] years; P = .02) and showed earlier cognitive decline. Locally estimated scatterplot smoothing curves further showed between-group differences in biomarker trajectories with age as reflected by nonoverlapping CIs. Specifically, carriers showed lower levels of the CSF Aβ1-42 to Aβ1-40 ratio until age 40 years, earlier increases in amyloid PET and plasma pTau181, and earlier loss of cortical metabolism and hippocampal volume. No differences were found in NfL biomarkers or CSF total tau and pTau181. Voxelwise analyses showed lower metabolism in subcortical and parieto-occipital structures and lower medial temporal volume in APOE ɛ4 allele carriers. Conclusions and Relevance In this study, the APOE ɛ4 allele was associated with earlier clinical and biomarker changes of AD in DS. These results provide insights into the mechanisms by which APOE increases the risk of AD, emphasizing the importance of APOE genotype for future clinical trials in DS.

Deep brain stimulation (DBS) has been found to be effective in treatment resistant neurological and psychiatric disorders. So far there has been only one completed trial in schizophrenia, in which seven treatment resistant patients received DBS in the subgenual anterior cingulate cortex (sgACC, N = 4) or the nucleus accumbens (NAc, N = 3); four met symptomatic response criteria over the trial period. Six patients underwent 18 F-FDG PET at baseline and after at least 6 months of stimulation. Individual patient analysis indicated that DBS to both the sgACC and NAc was associated with local and distant changes in glucose metabolism. Increments and decrements of brain activity were observed in regions that included the medial prefrontal cortex, the dorsolateral prefrontal cortex, the anterior cingulate cortex, the caudate nucleus, the NAc, the hippocampus and the thalamus. Increased activity appeared to be associated with clinical improvement. These preliminary findings suggest that DBS acts by modulating cerebral activity in the cortico-basal-thalamic-cortical circuit in patients with schizophrenia who show improvement in psychotic symptoms.

Background: Alzheimer's disease and its complications are the leading cause of death in adults with Down syndrome. Studies have assessed Alzheimer's disease in individuals with Down syndrome, but the natural history of biomarker changes in Down syndrome has not been established. We characterised the order and timing of changes in biomarkers of Alzheimer's disease in a population of adults with Down syndrome. Methods: We did a dual-centre cross-sectional study of adults with Down syndrome recruited through a population-based health plan in Barcelona (Spain) and through services for people with intellectual disabilities in Cambridge (UK). Cognitive impairment in participants with Down syndrome was classified with the Cambridge Cognitive Examination for Older Adults with Down Syndrome (CAMCOG-DS). Only participants with mild or moderate disability were included who had at least one of the following Alzheimer's disease measures: apolipoprotein E allele carrier status; plasma concentrations of amyloid ß peptides 1–42 and 1–40 and their ratio (Aß1–42/1–40), total tau protein, and neurofilament light chain (NFL); tau phosphorylated at threonine 181 (p-tau), and NFL in cerebrospinal fluid (CSF); and one or more of PET with 18F-fluorodeoxyglucose, PET with amyloid tracers, and MRI. Cognitively healthy euploid controls aged up to 75 years who had no biomarker abnormalities were recruited from the Sant Pau Initiative on Neurodegeneration. We used a first-order locally estimated scatterplot smoothing curve to determine the order and age at onset of the biomarker changes, and the lowest ages at the divergence with 95% CIs are also reported where appropriate. Findings: Between Feb 1, 2013, and June 28, 2019 (Barcelona), and between June 1, 2009, and Dec 31, 2014 (Cambridge), we included 388 participants with Down syndrome (257 [66%] asymptomatic, 48 [12%] with prodromal Alzheimer's disease, and 83 [21%] with Alzheimer's disease dementia) and 242 euploid controls. CSF Aß1–42/1–40 and plasma NFL values changed in individuals with Down syndrome as early as the third decade of life, and amyloid PET uptake changed in the fourth decade. 18F-fluorodeoxyglucose PET and CSF p-tau changes occurred later in the fourth decade of life, followed by hippocampal atrophy and changes in cognition in the fifth decade of life. Prodromal Alzheimer's disease was diagnosed at a median age of 50·2 years (IQR 47·5–54·1), and Alzheimer's disease dementia at 53·7 years (49·5–57·2). Symptomatic Alzheimer's disease prevalence increased with age in individuals with Down syndrome, reaching 90–100% in the seventh decade of life. Interpretation: Alzheimer's disease in individuals with Down syndrome has a long preclinical phase in which biomarkers follow a predictable order of changes over more than two decades. The similarities with sporadic and autosomal dominant Alzheimer's disease and the prevalence of Down syndrome make this population a suitable target for Alzheimer's disease preventive treatments. Funding: Instituto de Salud Carlos III, Fundació Bancaria La Caixa, Fundació La Marató de TV3, Medical Research Council, and National Institutes of Health. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license

PMR is a common inflammatory rheumatic disease. Although its clinical characteristics are fully recognized, no specific test for its diagnosis has been established to date. Several studies have described a wide variety of diseases that present with polymyalgic symptoms. A 18FDG-PET/CT scan could help to deal with these differential diagnoses. The goal of our study is to describe the findings of the 18FDG-PET/CT scan in a cohort of PMR patients and to detail how the 18FDG-PET/CT scan improves accuracy when diagnosing other underlying conditions. This cross-sectional study enrolled patients with a diagnosis of PMR who underwent to a 18FDG-PET/CT scan to rule out other diagnosis. The 18FDG-PET/CT scan was performed either following clinical criteria at the onset of clinical symptoms or when the patient became PMR steroid resistant. Patients’ demographic, clinical and analytical data at the moment of the 18FDG-PET/CT scan were recorded. The final diagnosis was confirmed according to clinical judgement. A total of 103 patients with PMR were included. In 49.51% of patients, the 18FDG-PET/CT scan was ordered to study resistance to steroid therapy. The final diagnoses of patients were PMR in 70.9% patients, large vessel vasculitis in 15.5%, neoplasms 4.8% and another diagnosis in the rest. The 18FDG-PET/CT scan is a very useful technique for the study of Polymyalgia Rheumatica, not only to help in the diagnostic process, but also due to its role in the identification of a variety of PMR-like patrons.

Objective To compare detectability of hyperfunctioning parathyroid tissue (HPT) by digital and analog 18F-fluorocholine PET/CT in patients with primary hyperparathyroidism and negative/inconclusive 99mTc-MIBI scintigraphy-SPECT/CT. Materials and methods Thirty-three patients with primary hyperparathyroidism and negative/inconclusive 99mTc-MIBI scintigraphy-SPECT/CT were prospectively included. All patients accepted to be scanned by digital and analog PET/CT in the same imaging session after a single injection of 18F-fluorocholine. Three nuclear medicine physicians evaluated the digital and analog PET/CT datasets to assess the detection rate of HPT. Maximum standard uptake values (SUVmax) of HPT and locoregional lymph nodes were measured in both systems. Results HPT was detected in 30/33 patients by the digital system, whereas it was detected in 22/33 patients by the analog system (p < 0.01). Moreover, in 21 of these 33 patients, both systems detected one focal 18F-fluorocholine uptake, and in one patient the digital system detected two foci. Histopathology demonstrated HPT in 32 patients and it was inconclusive in one patient. The digital PET/CT detected HPT in 29 of the 32 patients, and the analog system in 22 of the 32 (p < 0.01). All HPT suspected lesions resected and detected only by the digital system (n = 8) were < 10 mm (7.5 +/- 1.3 mm), while those detected by both systems (n = 22) were > 10 mm (13 +/- 3.8 mm). SUVmax of HPT lesions was significantly higher than SUVmax of locoregional lymph node independently of the PET/CT system used (4.5 +/- 1.9 vs. 2.9 +/- 1.3, p < 0.0001). Conclusions Digital PET/CT offers superior performance over analog system in patients with suspected HPT and previous negative/inconclusive imaging examinations, particularly in sub-centimeter lesions. SUVmax can help in the differentiation between HTP and locoregional lymph nodes.

Objective: To identify brain regions whose metabolic impairment contributes to dementia with Lewy bodies (DLB) clinical core features expression and to assess the influence of severity of global cognitive impairment on the DLB hypometabolic pattern. Methods: Brain fluorodeoxyglucose positron emission tomography and information on core features were available in 171 patients belonging to the imaging repository of the European DLB Consortium. Principal component analysis was applied to identify brain regions relevant to the local data variance. A linear regression model was applied to generate core-feature–specific patterns controlling for the main confounding variables (Mini-Mental State Examination [MMSE], age, education, gender, and center). Regression analysis to the locally normalized intensities was performed to generate an MMSE-sensitive map. Results: Parkinsonism negatively covaried with bilateral parietal, precuneus, and anterior cingulate metabolism; visual hallucinations (VH) with bilateral dorsolateral–frontal cortex, posterior cingulate, and parietal metabolism; and rapid eye movement sleep behavior disorder (RBD) with bilateral parieto-occipital cortex, precuneus, and ventrolateral–frontal metabolism. VH and RBD shared a positive covariance with metabolism in the medial temporal lobe, cerebellum, brainstem, basal ganglia, thalami, and orbitofrontal and sensorimotor cortex. Cognitive fluctuations negatively covaried with occipital metabolism and positively with parietal lobe metabolism. MMSE positively covaried with metabolism in the left superior frontal gyrus, bilateral–parietal cortex, and left precuneus, and negatively with metabolism in the insula, medial frontal gyrus, hippocampus in the left hemisphere, and right cerebellum. Interpretation: Regions of more preserved metabolism are relatively consistent across the variegate DLB spectrum. By contrast, core features were associated with more prominent hypometabolism in specific regions, thus suggesting a close clinical–imaging correlation, reflecting the interplay between topography of neurodegeneration and clinical presentation in DLB patients. Ann Neurol 2019;85:715–725.

ObjectiveThe purpose of this study was to compare image quality and lesion detection capability between a digital and an analog PET/CT system in oncological patients.Materials and methodsOne hundred oncological patients (62 men, 38 women; mean age of 6512years) were prospectively included from January-June 2018. All patients, who accepted to be scanned by two systems, consecutively underwent a single day, dual imaging protocol (digital and analog PET/CT). Three nuclear medicine physicians evaluated image quality using a 4-point scale (-1, poor; 0, fair; 1, good; 2, excellent) and detection capability by counting the number of lesions with increased radiotracer uptake. Differences were considered significant for a p value

The correct administered activity of 18F-FCH is 0.1-0.14 mCi/Kg, which is equivalent to 3.7-5.2 MBq/kg.

Purpose Huntington's disease (HD) is a fatal neurodegenerative disorder with no effective treatment currently available. Although the pathological hallmark of HD is massive striatal atrophy, it has been suggested that cortical deterioration may concomitantly occur and play a major role in the patient's functional independence. Our objective was to characterize cortical structural and metabolic neurodegeneration in the transition from premanifest to early-stage Huntington's disease (HD). Methods Using a surface-based neuroimaging approach, we compared cortical thickness and intracortical FDG-PET uptake in 19 early-symptomatic HD patients with respect to 21 premanifest HD individuals. Results Early-HD patients showed significant cortical atrophy and intracortical hypometabolism when compared to premanifest subjects (p < 0.05, corrected for multiple comparisons). However, whereas the atrophy pattern was restricted to precentral and parieto-occipital regions, a pronounced frontotemporal hypometabolism was observed. Importantly, structural changes correlated with motor and cognitive performance, and metabolic changes were associated with the presence and severity of apathy in this population, a core neuropsychiatric feature of this disorder. Conclusion Our findings reveal an asynchronous neuronal loss and metabolic compromise across the cerebral cortex in early HD. Hence, the use of structural and metabolic imaging indicators to characterize disease progression in this population should take into consideration the dissociation which occurs between cortical atrophy and hypometabolism.

PurposeThe purpose of this study was to assess whether digital photon counting technology in digital PET/CT influences the quantification of SUVmax in target lesions and regions of reference compared to analog PET/CT before an interchangeable use of either system in follow up studies.MethodsFrom January to June of 2018, 100 oncological patients underwent successive PET/CT imaging with digital and analog systems in the same day. Fifty-eight patients underwent analog imaging first and digital imaging thereafter, and 42 patients the other way round. SUVmax was measured in reference regions (liver and mediastinal blood pool) and in the most metabolically active target lesion in each patient. According to the sequence order of PET/CT acquisition, two groups of SUVmax values were obtained, i.e. group 1: analog PET/CT performed first; group 2: digital PET/CT performed first.ResultsMean SUVmax in the total sample (regardless of the order of PET/CT acquisition) in the target lesions with the analog PET/CT was 8.146.39 and the digital 9.976.14 (P=0.000). Total mean SUVmax in the liver with the analog was 4.392.59 and the digital 4.463.18 (P=0.477). Total mean SUVmax in the mediastinal blood pool with the analog was 2.30 +/- 0.67 and the digital 2.54 +/- 0.74 (P=0.000).Group 1: mean SUVmax in the target lesions with the analog system was 6.64 +/- 4.71 and the digital 9.48 +/- 5.60 (P=0.000). Mean liver SUVmax with the analog was 4.70 +/- 2.90 and the digital 4.80 +/- 3.72 (P=0.088). Mediastinal blood pool SUVmax with the analog was 2.33 +/- 0.66 and the digital 2.45 +/- 0.73 (P=0.041).Group 2: mean SUVmax in target lesions with the digital system was 10.63 +/- 6.88 and the analog 10.16 +/- 7.76 (P=0.046). Mean liver SUVmax with the digital was 3.99 +/- 2.20 and the analog 3.96 +/- 2.04 (P=0.218). Mediastinal blood pool SUVmax with the digital was 2.66 +/- 0.75 and the analog 2.27 +/- 0.68 (P=0.000).No significant differences between both time delays were found.ConclusionsImproved photon counting technology in the digital PET/CT, and the effect of delayed increased uptake and retention significantly increases SUVmax values. This has to be taken into account before interchangeable use of either system in follow up studies.

Background The purpose of this study is to evaluate the prognostic significance of nodes with extracapsular spread (ECS) in patients treated with a planned neck dissection after chemoradiotherapy. Methods We carried out a retrospective study of 109 cN+ patients who achieved a complete response in the primary location after chemoradiotherapy and treated with a planned neck dissection. Results The 5-year disease-specific survival for patients without residual metastatic nodes in the neck dissection (pN0, n = 69) was 75.7% (95% CI: 64.4%-87.0%). For patients with metastatic nodes without ECS (pN+/ECS-negative, n = 17), the corresponding figure was 74.0% (95% CI: 48.2%-99.8%), and for patients with metastatic neck nodes with ECS (pN+/ECS-positive, n = 23) it was 8.7% (95% CI: 0.0%-24.3%) (P = .0001). Conclusion The presence of ECS in the pathologic study of the planned neck dissections carried out after chemoradiotherapy in patients with human papillomavirus-negative (HPV-negative) head and neck squamous cell carcinoma (SCC) allows identification of a group of patients with a high risk of failure.

The article Digital vs. analog PET/CT: intra-subject comparison of the SUVmax in target lesions and reference regions, written by Francisco Fuentes-Ocampo, Diego Alfonso Lopez-Mora, Albert Flotats, Gabriela Paillahueque

Levels above 75% of striatal dopamine 2 receptor occupancy (D2RO) have been associated with extrapyramidal symptoms (EPS). The aim of the present study is to investigate the relationship between D2RO and EPS in a sample of psychotic patients in current treatment with both typical and atypical antipsychotics. Brain iodine-123-iodobenzamide single photon emission computed tomography (I-123-IBZM SPECT) was performed in 81 patients taking stable doses of haloperidol, risperidone, olanzapine, quetiapine, clozapine or ziprasidone. First, the degree of D2RO and Positive and Negative Syndrome Scale (PANSS) scores was compared between the group of patients who presented EPS and the group free of EPS. Afterwards, these variables were compared among the different antipsychotic medications. The group with EPS presented means of D2RO significantly higher than the group free of EPS. Significant differences in D2RO were found in clozapine, quetiapine and ziprasidone groups compared with the haloperidol group. No differences were observed between either olanzapine or risperidone and haloperidol. No quetiapine- or clozapine-treated patients developed EPS. Haloperidol and risperidone demonstrated a relationship between striatal D2RO and EPS. The findings suggest that higher D2RO is related to appearance of EPS. Occupancy in the group with EPS was in agreement with previous studies that suggested a high degree of D2RO is necessary for the occurrence of EPS. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

The Multidimensional Alcohol Craving Scale (MACS) and Single Photon Emission Computerized Tomography (SPECT) with (123)I-iodobenzamide ((123)I-IBZM) can be useful tools for assessing relapse risk in early recovery from alcohol-dependency. The aim of this study was to assess possible relationships between MACS score, (123)I-IBZM binding and time to first heavy drinking day (TFHD) after detoxification treatment.Nineteen alcohol-dependent in-patients were evaluated by MACS scale and an 123I-IBZM-SPECT, performed following alcohol detoxification treatment. At discharge, participants were advised to take naltrexone 50 mg/day for relapse prevention. TFHD was assessed over a 12-week follow up.The MACS score at the beginning of the detoxification process and naltrexone treatment after detoxification were independent predictive factors for TFHD.The MACS scale is a better predictor of TFHD than IBZM binding. It is simple, non-invasive and inexpensive and appears to be a useful instrument both for clinical practice and for research.

There is as yet no definite prognostic marker to determine whether a first-episode psychosis will become schizophrenia or not. The aim of the present study is to address whether the mechanism of sensitization of the subcortical dopaminergic pathway yielding to an increase of the postsynaptic D2 receptors may serve as a prognostic marker of clinical outcome in drug naive patients with a first-episode psychosis, by means of a prospective and multicentric study with untreated first-episode psychosis patients (n=37). 123I-IBZM SPECT was performed at the time of the inclusion in the study, before antipsychotic medication was initiated. One year later, patients were assessed again so as to determine their diagnosis. There was a significant group effect at baseline in D2 Striatal/Frontal (S/F) ratios (F=10.2, p

The biological basis of the association between cannabis-induced dopamine dysregulation and psychosis remains poorly understood. This (123)I-IBZM SPECT study assessed striatal dopamine D2 receptor (D2R) binding in 37 untreated first-episode psychosis (FEP) subjects, and 18 healthy controls. The aim was to examine if there were differences between FEP subjects with (n=14) and without (n=23) cannabis use in uptake ratios in the D2R. Striatal/Frontal cortex (S/F) uptake ratios were obtained. Healthy controls showed the lowest D2R binding ratios. No differences were found in S/F ratios between users and non-users, suggesting similar dopaminergic mechanisms underlying psychotic symptoms in both groups. (C) 2011 Elsevier B.V. All rights reserved.

The sympathetic nervous system has great influence on cardiovascular physiology, and the importance of cardiac innervation abnormalities in the physiopathology of various cardiac diseases has been emphasized. Cardiac neurotransmission imaging with single-photon emission computed tomography (SPECT) allows in vivo assessment of the myocardial nervous system. At present, the most commonly used SPECT tracer to assess cardiac neurotransmission is metaiodobenzylguanidine labelled with iodine-123 ( 123 I-MIBG). In patients with heart transplantation, ischemic heart disease, dysautonomias and drug-induced cardiotoxicity, assessment of neuronal function can help characterise the disease and improve the prognostic stratification. Cardiac 123 I-MIBG scintigraphy allows autonomic neuropathy to be detected in the early stages of diabetes mellitus. In patients with heart failure, the assessment of cardiac sympathetic activity has important prognostic implications. Future directions in cardiac sympathetic neurotransmission include the development of new tracers, targeting of second-messenger molecules and early assessment of cardiac neurotransmission in genetically predisposed subjects for prevention of heart failure.

Objetivos: La Escala Multidimensional de Craving de Alcohol (EMCA) y la Tomografia Computarizada por emision de Foton Simple (SPECT) con 123I-yodobenzamida (IBZM) pueden ser instrumentos validos para evaluar el riesgo de recaida, durante la etapa inicial de la recuperacion del trastorno por dependencia del alcohol. El objetivo de este estudio es evaluar las posibles relaciones entre la escala EMCA y la captacion de IBZM y el tiempo hasta el primer consumo excesivo de alcohol (TPCEA) una vez finalizado el tratamiento de desintoxicacion. Metodologia: Diecinueve pacientes hospitalizados han sido evaluados mediante la escala EMCA y la SPECT con IBZM al finalizar el tratamiento de desintoxicacion del alcohol. En el momento del alta se les aconsejo seguir un tratamiento con naltrexona 50 mg/dia para la prevencion de recaidas. El TPCEA ha sido evaluado durante 12 semanas de seguimiento. Resultados: La puntuacion de la escala EMCA, al inicio del proceso de desintoxicacion, y el seguimiento de un tratamiento con naltrexona, posteriormente a dicho proceso, fueron factores predictivos independientes del TPCEA. Conclusiones: La escala EMCA se ha mostrado como un buen predictor del TPCEA mientras que la captacion de IBZM parece no serlo. La escala EMCA parece presentar una mayor utilidad, tanto clinica como para la investigacion, frente a evaluaciones mas complejas, invasivas y costosas.