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ObjectiveTo investigate the types of errors produced in a picture naming task by patients with neurodegenerative dementia due to different etiologies and their neural correlates.MethodsThe same standardized picture naming test was administered to a consecutive sample of patients (n = 148) who had been studied with [18F] FDG-PET. The errors were analyzed in 3 categories (visual, semantic, and phonologic). The PET data were analyzed using an optimized single-subject procedure, and the statistical parametric mapping multiple regression design was used to explore the correlation between each type of error and brain hypometabolism in the whole group. Metabolic connectivity analyses were run at the group level on 7 left hemisphere cortical areas corresponding to an a priori defined naming network.ResultsSemantic errors were predominant in most patients, independent of clinical diagnosis. In the whole group analysis, visual errors correlated with hypometabolism in the right inferior occipital lobe and in the left middle occipital lobe. Semantic errors correlated with hypometabolism in the left fusiform gyrus, the inferior and middle temporal gyri, and the temporal pole. Phonologic errors were associated with hypometabolism in the left superior and middle temporal gyri. Both positive (occipital–posterior fusiform) and negative (anterior fusiform gyrus and the superior anterior temporal lobe) connectivity changes were associated with semantic errors.ConclusionsNaming errors reflect the dysfunction of separate stages of the naming process and are specific markers for different patterns of brain involvement. These correlations are not limited to primary progressive aphasia but extend to other neurodegenerative dementias.

The main aim of this study is to improve our knowledge on Internet Gaming Disorder (IGD), contributing to a common discourse concerning its risk profiles. Specifically, the study aims to assess the prevalence of addicted gamers among Italian online and offline gamers, accounting for gender and to investigate the mediation role of gaming motives on the relationship between personality risk traits and IGD. A total of 627 videogame players (55% women; mean age 27 years) recruited from social networking sites took part in the study and filled a questionnaire including gaming characteristics, the Internet Gaming Disorder Scale (IGDS9-SF), the Substance Use Risk Profile Scale (SURPS) and the Motives for Online Gaming Questionnaire (MOGQ). The prevalence rate of Internet gaming disorder was 5.3%. Hopelessness was the personality dimension that most differentiates gaming addicts from non-addicts. Results of the mediation model suggested that Hopelessness was both directly and indirectly (via escape, fantasy and recreational motives) associated with IGD. The motivations Escape and Fantasy also mediate between Anxiety sensitivity and IGD while Competition mediate between Sensation seeking trait and IGD. The evidence suggests that IGD is motivated by psychological mechanisms similar to those compelling substance abuse, but with its own unique features.RésuméCette étude a pour but d’améliorer notre connaissance de la dépendance au jeu sur Internet (DJI) afin d’enrichir le discours sur ses profils de risque. Elle vise plus précisément à évaluer la prévalence des joueurs dépendants parmi les joueurs italiens en ligne et hors ligne, en tenant compte du genre et en examinant le rôle de médiation des raisons qui motivent la pratique des jeux dans la relation entre les traits de personnalité présentant des risques et la DJI. En tout, 627 joueurs de jeux vidéo (55 % de femmes d’une moyenne d’âge de 27 ans) recrutés sur des sites de réseaux sociaux ont participé à l’étude et rempli un questionnaire comprenant des caractéristiques liées au jeu, l’échelle de la dépendance au jeu sur Internet (IGDS9-SF), l’échelle de profil de risque de consommation de substances psychoactives (SURPS) et le questionnaire sur les raisons de jouer en ligne (MOGQ). Le taux de prévalence de la dépendance au jeu sur Internet s’établissait à 5,3 %. Le désespoir constituait l’aspect de la personnalité qui distinguait le plus les personnes dépendantes au jeu des personnes non dépendantes. Les résultats du modèle de médiation donnaient à penser que le désespoir était associé directement et indirectement (raisons liées à la fuite, à l’imaginaire et aux loisirs) à la DJI. Les raisons Fuite et Imaginaire assurent la médiation entre la sensibilité à l’anxiété et la DJI, tandis que la concurrence assure la médiation entre la recherche de sensations et la DJI. Tout indique que la DJI est motivée par des mécanismes psychologiques similaires à ceux qui incitent à la toxicomanie, mais possède ses propres caractéristiques.

BACKGROUND Alzheimer's disease (AD) diagnosis can be hindered by amyloid biomarkers discordances. OBJECTIVE We aim to interpret discordances between amyloid positron emission tomography (Amy-PET) and cerebrospinal fluid (CSF) (Aβ42 and Aβ42/40), using Amy-PET semiquantitative analysis, [18F]fluorodeoxyglucose (FDG)-PET pattern, and CSF assays. METHOD Thirty-six subjects with dementia or mild cognitive impairment, assessed by neuropsychological tests, structural and functional imaging, and CSF assays (Aβ42, Aβ42/40, p-tau, t-tau), were retrospectively examined. Amy-PET and FDG-PET scans were analyzed by visual assessment and voxel-based analysis. SUVR were calculated on Amy-PET scans. RESULTS Groups were defined basing on the agreement among CSF Aβ42 (A), CSF Aβ42/40 Ratio (R), and Amy-PET (P) dichotomic results ( ±). In discordant groups, CSF assays, Amy-PET semiquantification, and FDG-PET patterns supported the diagnosis suggested by any two agreeing amyloid biomarkers. In groups with discordant CSF Aβ42, the ratio always agrees with Amy-PET results, solving both false-negative and false-positive Aβ42 results, with Aβ42 levels close to the cut-off in A + R-P- subjects. The A + R + P- group presented high amyloid deposition in relevant areas, such as precuneus, posterior cingulate cortex (PCC) and dorsolateral frontal inferior cortex at semiquantitative analysis. CONCLUSION The amyloid discordant cases could be overcome by combining CSF Aβ42, CSF ratio, and Amy-PET results. The concordance of any 2 out of the 3 biomarkers seems to reveal the remaining one as a false result. A cut-off point review could avoid CSF Aβ42 false-negative results. The regional semiquantitative Amy-PET analysis in AD areas, such as precuneus and PCC, could increase the accuracy in AD diagnosis.

Background: Discordance among amyloid biomarkers is a challenge to overcome in order to increase diagnostic accuracy in dementia. Objectives: 1) To verify that cerebrospinal fluid (CSF) Aβ42/Aβ40 ratio (AβR) better agrees with Amyloid PET (Amy-PET) results compared to CSF Aβ42; 2) to detect differences among concordant positive, concordant negative, and discordant cases, basing the concordance definition on the agreement between CSF AβR and Amy-PET results; 3) to define the suspected underlying pathology of discordant cases using in vivo biomarkers. Method: We retrospectively enrolled 39 cognitively impaired participants in which neuropsychological tests, apolipoprotein E genotype determination, TC/MRI, FDG-PET, Amy-PET, and CSF analysis had been performed. In all cases, CSF analysis was repeated using the automated Lumipulse method. In discordant cases, FDG-PET scans were evaluated visually and using automated classifiers. Results: CSF AβR better agreed with Amy-PET compared to CSF Aβ42 (Cohen’s K 0.431 versus 0.05). Comparisons among groups did not show any difference in clinical characteristics except for age at symptoms onset that was higher in the 6 discordant cases with abnormal CSF AβR values and negative Amy-PET (CSF AβR+/AmyPET–). FDG-PET and all CSF markers (Aβ42, AβR, p-Tau, t-Tau) were suggestive of Alzheimer’s disease (AD) in 5 of these 6 cases. Conclusion: 1) CSF AβR is the CSF amyloid marker that shows the better level of agreement with Amy-PET results; 2) The use of FDG-PET and CSF-Tau markers in CSFAβR+/Amy-PET–discordant cases can support AD diagnosis; 3) Disagreement between positive CSF AβR and negative Amy-PET in symptomatic aged AD patients could be due to the variability in plaques conformation and a negative Amy-PET scan cannot be always sufficient to rule out AD.

An early differentiation between Alzheimer’s Disease (AD) and other dementias is crucial for an adequate patients’ management, albeit it may result difficult for the occurrence of “atypical presentations.” Current diagnostic criteria recognize the importance of biomarkers for AD diagnosis, but still an optimal diagnostic work-up isn’t available. Evaluate the utility and reproducibility of biomarkers and propose an “optimal” diagnostic work-up in atypical dementia. (1) a retrospective selection of “atypical dementia cases”; (2) a repetition of diagnostic assessment by two neurologists following two different diagnostic work-ups, each consisting of multiple steps; (3) a comparison between diagnostic accuracy and confidence reached at each step by both neurologists and evaluation of the inter-rater agreement. In AD, regardless of the undertaken diagnostic work-up, a significant gain in accuracy was reached by both neurologists after the second step, whereas in frontotemporal dementia (FTD), adding subsequent steps was not always sufficient to increase significantly the baseline accuracy. A relevant increment in diagnostic confidence was detectable after studying pathophysiological markers in AD, and after assessing brain metabolism in FTD. The inter-rater agreement was higher at the second step for the AD group when the pathophysiological markers were available and for the FTD group when the results of FDG-PET were accessible. In atypical cases of dementia, biomarkers significantly raise diagnostic accuracy, confidence, and agreement. This study introduces a proof of diagnostic work-up that combines imaging and CSF biomarkers and suggests distinct ways to proceed on the basis of a greater diagnostic likelihood.

ObjectiveTo examine in a 3-year brain imaging study the effects of higher vs lower adherence to a Mediterranean-style diet (MeDi) on Alzheimer disease (AD) biomarker changes (brain β-amyloid load via 11C-Pittsburgh compound B [PiB] PET and neurodegeneration via 18F-fluorodeoxyglucose [FDG] PET and structural MRI) in midlife.MethodsSeventy 30- to 60-year-old cognitively normal participants with clinical, neuropsychological, and dietary examinations and imaging biomarkers at least 2 years apart were examined. These included 34 participants with higher (MeDi+) and 36 with lower (MeDi−) MeDi adherence. Statistical parametric mapping and volumes of interest were used to compare AD biomarkers between groups at cross section and longitudinally.ResultsMeDi groups were comparable for clinical and neuropsychological measures. At baseline, compared to the MeDi+ group, the MeDi− group showed reduced FDG-PET glucose metabolism (CMRglc) and higher PiB-PET deposition in AD-affected regions (p < 0.001). Longitudinally, the MeDi−-group showed CMRglc declines and PiB increases in these regions, which were greater than those in the MeDi+ group (pinteraction < 0.001). No effects were observed on MRI. Higher MeDi adherence was estimated to provide 1.5 to 3.5 years of protection against AD.ConclusionLower MeDi adherence was associated with progressive AD biomarker abnormalities in middle-aged adults. These data support further investigation of dietary interventions for protection against brain aging and AD.

Objective:This observational multimodality brain imaging study investigates emergence of endophenotypes of late-onset Alzheimer disease (AD) risk during endocrine transition states in a cohort of clinically and cognitively normal women and age-matched men.Methods:Forty-two 40- to 60-year-old cognitively normal women (15 asymptomatic perimenopausal by age [CNT], 13 perimenopausal [PERI], and 14 postmenopausal [MENO]) and 18 age- and education-matched men were examined. All patients had volumetric MRI, 18F-fluoro-2-deoxyglucose (FDG)–PET (glucose metabolism), and Pittsburgh compound B–PET scans (β-amyloid [Aβ] deposition, a hallmark of AD pathology).Results:As expected, the MENO group was older than the PERI and CNT groups. Otherwise, groups were comparable on clinical and neuropsychological measures and APOE4 distribution. Compared to CNT women and to men, and controlling for age, PERI and MENO groups exhibited increased indicators of AD endophenotype, including hypometabolism, increased Aβ deposition, and reduced gray and white matter volumes in AD-vulnerable regions (p < 0.001). AD biomarker abnormalities were greatest in MENO, intermediate in PERI, and lowest in CNT women (p < 0.001). Aβ deposition was exacerbated in APOE4-positive MENO women relative to the other groups (p < 0.001).Conclusions:Multimodality brain imaging indicates sex differences in development of the AD endophenotype, suggesting that the preclinical AD phase is early in the female aging process and coincides with the endocrine transition of perimenopause. These data indicate that the optimal window of opportunity for therapeutic intervention in women is early in the endocrine aging process.

BACKGROUND AND PURPOSE: Stress‐related catecholamines have a role in cancer and β‐adrenoceptors; specifically, β(2)‐adrenoceptors have been identified as new targets in treating melanoma. Recently, β(3)‐adrenoceptors have shown a pleiotropic effect on melanoma micro‐environment leading to cancer progression. However, the mechanisms by which β(3)‐adrenoceptors promote this progression remain poorly understood. Catecholamines affect the immune system by modulating several factors that can alter immune cell sub‐population homeostasis. Understanding the mechanisms of cancer immune‐tolerance is one of the most intriguing challenges in modern research. This study investigates the potential role of β(3)‐adrenoceptors in immune‐tolerance regulation. EXPERIMENTAL APPROACH: A mouse model of melanoma in which syngeneic B16‐F10 cells were injected in C57BL‐6 mice was used to evaluate the effect of β‐adrenoceptor blockade on the number and activity of immune cell sub‐populations (Treg, NK, CD8, MDSC, macrophages, and neutrophils). Pharmacological and molecular approaches with β‐blockers (propranolol and SR59230A) and specific β‐adrenoceptor siRNAs targeting β(2)‐ or β(3)‐adrenoceptors were used. KEY RESULTS: Only β(3)‐, but not β(2)‐adrenoceptors, were up‐regulated under hypoxia in peripheral blood mononuclear cells and selectively expressed in immune cell sub‐populations including Treg, MDSC, and NK. SR59230A and β(3)‐adrenoceptor siRNAs increased NK and CD8 number and cytotoxicity, while they attenuated Treg and MDSC sub‐populations in the tumour mass, blood, and spleen. SR59230A and β(3)‐adrenoceptor siRNAs increased the ratio of M1/M2 macrophages and N1 granulocytes. CONCLUSIONS AND IMPLICATIONS: Our data suggest that β(3)‐adrenoceptors are involved in immune‐tolerance, which opens the way for new strategic therapies to overcome melanoma growth. LINKED ARTICLES: This article is part of a themed section on Adrenoceptors—New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc

Quantitative maps of cerebral metabolic rate of glucose (CMRGlu) from fluorine-18 fluorodeoxyglucose-PET are useful in brain studies, but are challenging to acquire because of technical constraints, which hinder their use in clinical routine. Aortic image-derived input functions (IDIFs) combined with Sokoloff's method were proposed as a suitable solution. However, Sokoloff's method requires the use of standard kinetic constants, which may produce biased estimates. Patlak's method would be more appropriate, but concern can arise when used with an aortic IDIF from unavailability of a complete brain curve acquired starting from injection. The aim of this study was to develop a CMRGlu quantification technique that combines Patlak's method with aortic IDIFs in a clinical setting.A simple acquisition protocol for aortic IDIF measurement was developed and applied on a sample of patients with different degrees of hypometabolism (one healthy control, four patients with a neurodegenerative condition, and one coma patient). CMRGlu estimates in vivo were obtained with both the Sokoloff method and the Patlak method. Computer simulations were performed to assess the causes of bias affecting Sokoloff and Patlak estimates and interpret the results obtained in patients.Simulations showed that Sokoloff's method is less stable than Patlak's method as the extent of bias changed across different physiological states, potentially leading to misinterpretation of clinical data. In clinical patients, Sokoloff and Patlak estimates were correlated on the whole, but deviations emerged for critical physiological states.CMRGlu quantification with the Patlak method and aortic IDIF is feasible, easy to implement in clinical practice, and superior to Sokoloff's method from a personalized medicine perspective.

Aims: To evaluate the incidence of severe preeclampsia, eclampsia and HELLP syndrome in a tertiary Hospital Centre of Obstetrics and Gynaecology and to identify the impact of risk factors associated with severe preeclampsia. Study Design: Retrospective cross-sectional study. Place and Duration of Study: University Hospital of Obstetrics and Gynaecology “Koco Gliozheni”, Tirana, Albania between January 2009 and December 2013. Methodology: To collect the data for this study we used the medical records of births of a period of five years. The standard inclusion criteria in the study were pregnant women diagnosed with preeclampsia that had delivered in this hospital after 24 weeks’ gestation despite the number of the babies, fetal presentation and mode of delivery. The exclusion criteria in this study were: pregnancies with confirmed fetal anomalies non-viable, pregnancies with missing data, and pregnancies with unknown gestational age. The maternal variables collected from the medical Original Research Article Ndoni et al.; BJMMR, 13(12): 1-7, 2016; Article no.BJMMR.24143 2 records were: maternal age, parity, gestational age at delivery, multiple pregnancy, pre-existing (chronic) hypertension, pre-existing diabetes mellitus, renal diseases and preeclampsia in previous pregnancy. The data collected for the variables were compared with the statistical data for all the deliveries during the study period. Fisher’s exact test, Chi-squared test and SPSS program were used as statistical methods. Results: The study found differences between the severe preeclampsia group and the general population for the maternal risk factors: severe preeclampsia was evaluated 16.8% vs. 3.5% (P< 0.01), pre-existing hypertension 7.8% vs. 2.3% (P = 0.02), renal diseases 1.9% vs. 1.1%, diabetes mellitus 5.8% vs. 4.6% and multiple pregnancies 7.1% vs. 2.7% respectively. Conclusion: Identification of these risk factors is very important for the calculation of risk for preeclampsia in early pregnancy and early treatment to prevent the maternal and perinatal morbidity and mortality from this disease.

As áreas verdes urbanas são percebidas de diferentes formas pelas pessoas, a depender de fatores culturais, sociais e sensoriais. Uma Instituição de Ensino Superior (IES) reunindo uma heterogeneidade de classes sociais e descendências étnicas torna-se um local de pesquisa que pode refletir diferentes percepções ambientais. O conhecimento de tal heterogeneidade serve de base para a construção de programas específicos de educação ambiental. Desta forma, o objetivo deste trabalho foi analisar a percepção e conhecimento de alunos de graduação presencial e funcionários da IES em relação às espécies de flora e áreas naturais do campus universitário. O método adotado foi a aplicação de entrevistas estruturadas contando questões abertas e fechadas. Os dados foram analisados quali e quantitativas. Foram 40 participantes, sendo 55% alunos e 45% funcionários. O número de espécies citadas pelos participantes variou entre 1 e 11 (± 2.93). Sobre as áreas naturais do campus a maioria dos entrevistados (73%) a declarou como "regular" segundo sua percepção, sendo alguma forma de utilidade ao homem as mais citadas, ficando as funções ecológicas com menor importância. Baseando-se no conceito da “cegueira botânica” os resultados mostram que os entrevistados apresentam dificuldade em perceber as plantas em seu cotidiano. Tendo a referida IES a divulgação de uma postura sustentável, esperamos que os resultados possam servir de base para o planejamento de projetos de Educação Ambiental envolvendo alunos e funcionários da instituição e comunidade externa em projetos de extensão universitária que contribuam para o alcance de uma comunidade acadêmica que contribua com seu pilar ambiental.

Despite epidemiological findings of improvements in cardiovascular risk factors with a light-to-moderate intake of alcohol, many misconceptions remain regarding alcohol intake and the risks and benefits of consumption. We sought to examine physician attitudes and recommendations regarding alcohol intake in a cohort of Argentine physicians and to establish their sources of knowledge. An online national survey was distributed through the Argentine Federation of Cardiology (FAC) to cardiologists, internal medicine specialists, general and other subspecialty physicians in Argentina. The survey was completed by 745 physicians, of whom 671 (90%) were cardiologists. In total, 35% of physicians viewed moderate alcohol intake to be beneficial for cardiovascular health, 36% believed only wine offered such benefits, 24% viewed any intake to be harmful, and 5% had other opinions. More than half (57%) self-reported their knowledge came from academic sources. Regarding knowledge of drinking guidelines, only 41% of physicians were aware of the concept of &ldquo, standard drink&rdquo, Physicians were generally not comfortable converting standard drinks into other metric units, however men tended to be more comfortable than women (p = 0.052). Physicians were not satisfied with their knowledge of drinking guidelines (3.01 &plusmn, 2.73, on a 0&ndash, 10 scale). Physicians were generally comfortable in counselling patients regarding safe limits of consumption (6.22 &plusmn, 3.20, on a 0&ndash, 10 scale). Argentine physicians were not satisfied with their knowledge of alcohol consumption guidelines or their understanding of the reported metrics. Only one-third of study participants viewed moderate alcohol intake as beneficial for cardiovascular health. This study shows the necessity to optimize the sources of knowledge.

After advanced age, female sex is the major risk factor for Alzheimer's disease (AD). The biological mechanisms underlying the increased AD risk in women remain largely undetermined. Preclinical studies identified the perimenopause to menopause transition, a neuroendocrine transition state unique to the female, as a sex-specific risk factor for AD. In animals, estrogenic regulation of cerebral glucose metabolism (CMRglc) falters during perimenopause. This is evident in glucose hypometabolism and decline in mitochondrial efficiency which is sustained thereafter. This study bridges basic to clinical science to characterize brain bioenergetics in a cohort of forty-three, 40-60 year-old clinically and cognitively normal women at different endocrine transition stages including premenopause (controls, CNT, n = 15), perimenopause (PERI, n = 14) and postmenopause (MENO, n = 14). All participants received clinical, laboratory and neuropsychological examinations, 18F-fluoro-deoxyglucose (FDG)-Positron Emission Tomography (PET) FDG-PET scans to estimate CMRglc, and platelet mitochondrial cytochrome oxidase (COX) activity measures. Statistical parametric mapping and multiple regression models were used to examine clinical, CMRglc and COX data across groups. As expected, the MENO group was older than PERI and controls. Groups were otherwise comparable for clinical measures and distribution of APOE4 genotype. Both MENO and PERI groups exhibited reduced CMRglc in AD-vulnerable regions which was correlated with decline in mitochondrial COX activity compared to CNT (p's0.001). A gradient in biomarker abnormalities was most pronounced in MENO, intermediate in PERI, and lowest in CNT (p0.001). Biomarkers correlated with immediate and delayed memory scores (Pearson's 0.26≤r≤0.32, p≤0.05). These findings validate earlier preclinical findings and indicate emergence of bioenergetic deficits in perimenopausal and postmenopausal women, suggesting that the optimal window of opportunity for therapeutic intervention in women is early in the endocrine aging process.

Primary bone lymphoma (PBL) is a rare disease. Little is reported about response evaluation procedures in these patients. Our aim was to evaluate response to therapy according to fluorodeoxyglucose-positron emission tomography (FDG-PET) results, and in particular to test the Deauville 5-point scale as compared to the visual evaluation of FDG-PET scans in PBL. In this single-center study, we diagnosed 31 consecutive patients with PBL, of which 24 were evaluated with end-of-treatment FDG-PET. Patients' ages ranged from 19 to 82 years. Six patients were treated with chemotherapy, 24 with chemotherapy and radiotherapy, and one patient with radiotherapy alone. Six patients were affected by a pathological fracture. Four patients died within the range of 3 to 36 months after diagnosis. The average follow-up of the remaining patients was 70 (24–173) months. Overall survival was 87% at 5 years. The only positive prognostic factor was complete remission after chemotherapy. According to visual criteria, end-of-treatment FDG-PET was evaluated in 24 patients and it was positive in 11 (46%) and negative in 13 patients. We organized a retrospective central-blinded revision of end-of-therapy FDG-PET scans using the 5-point Deauville Score (DS). We reviewed 17 out of 24 patients and obtained the following results: at the end of therapy, 12 patients with DS score 2, three patients with DS score 3, one patient with DS score 4, and none with DS score 5. Considering that all the 24 patients achieved complete remission after treatment, visual interpretation produced 11/24 false-positive results, and DS interpretation produced 1/17 false-positive results, thus significantly reducing the number of false positives. In PBL, the final evaluation at the end of therapy with FDG-PET should be evaluated using Deauville 5-point scale in order to significantly reduce the risk of false-positive scans.

Purpose Transmural abnormalities in myocardial blood flow (MBF) are important causes of ischaemia in patients with left ventricular (LV) hypertrophy. The study aimed to test whether pixel-wise parametric mapping of 13NH3 MBF can reveal transmural abnormalities in patients with hypertrophic cardiomyopathy (HCM).

A new risk gene associated with amyotrophic lateral sclerosis (ALS) has recently been identified: the Tank-binding kinase 1 (TBK1) gene. Up to now, 90 TBK1 variants have been described in ALS patients with or without frontotemporal dementia (FTD), thus making TBK1 the third or fourth most frequent genetic cause of ALS and FTD. A point mutation analysis in a cohort of 69 Italian ALS patients was performed in order to analyze the frequency of TBK1 mutations and the correlation with clinical phenotypes. The analysis identified the novel variant p.Tyr424Asp in a patient with a rapid progression of the disease. Our data supports the implication of TBK1 in ALS pathogenesis in Italy.

According to the literature, the APP Ala713Thr mutation is associated with Alzheimer's disease and cerebral amyloid angiopathy. We describe a case of dementia clinically compatible with frontotemporal dementia in an APP Ala713Thr mutation carrier in which both [18F]Florbetapir PET uptake and Aβ1-42 cerebrospinal fluid levels were normal. Further evidences are required to establish if this association is only incidental.

After advanced age, female sex is the major risk factor for Alzheimer’s disease (AD). The biological mechanisms underlying the increased AD risk in women remain largely undetermined. Preclinical studies identified the perimenopause to menopause transition, a neuroendocrine transition state unique to the female, as a sex-specific risk factor for AD. In animals, estrogenic regulation of cerebral glucose metabolism (CMRglc) falters during perimenopause. This is evident in glucose hypometabolism and decline in mitochondrial efficiency which is sustained thereafter. This study bridges basic to clinical science to characterize brain bioenergetics in a cohort of forty-three, 40–60 year-old clinically and cognitively normal women at different endocrine transition stages including premenopause (controls, CNT, n = 15), perimenopause (PERI, n = 14) and postmenopause (MENO, n = 14). All participants received clinical, laboratory and neuropsychological examinations, 18F-fluoro-deoxyglucose (FDG)-Positron Emission Tomography (PET) FDG-PET scans to estimate CMRglc, and platelet mitochondrial cytochrome oxidase (COX) activity measures. Statistical parametric mapping and multiple regression models were used to examine clinical, CMRglc and COX data across groups. As expected, the MENO group was older than PERI and controls. Groups were otherwise comparable for clinical measures and distribution of APOE4 genotype. Both MENO and PERI groups exhibited reduced CMRglc in AD-vulnerable regions which was correlated with decline in mitochondrial COX activity compared to CNT (p’s

The aim of this study was to investigate the predictive potential of pre-operative regional cerebral blood flow (rCBF) in the pre-supplementary motor area (pre-SMA) and clinical factors in Parkinson’s disease (PD) patients treated with subthalamic nucleus (STN) stimulation. Methods Ten patients underwent rCBF SPECT and motor Unified Parkinson’s Disease Rating Scale (UPDRS) preand post-operatively during stimulation at 5 and 42 months. Statistical parametric mapping (SPM) was used to extract rCBF values in the pre-SMA because it is related with motor improvement. Post-operative outcomes included motor response to stimulation and percent improvement in UPDRS. Pre-operative predictors were explored by correlation test, linear regression and multivariate analyses. Results Higher pre-operative rCBF in the pre-SMA and younger age were associated with favourable outcomes at 5 and 42 months. Pre-operative rCBF results were significantly associated with baseline clinical factors. Conclusion This study shows that PD patients with younger age have higher rCBF values in the pre-SMA and better outcome, thus giving the rationale to the hypothesis that STN stimulation could be considered early in the course of disease.

Epidemiological evidence linking diet, one of the most important modifiable lifestyle factors, and risk of Alzheimer's disease (AD) is rapidly increasing. However, there is little or no evidence for a direct association between dietary nutrients and brain biomarkers of AD. This study identifies nutrient patterns associated with major brain AD biomarkers in a cohort of clinically and cognitively normal (NL) individuals at risk for AD.Cross-sectional study.Manhattan (broader area).Fifty-two NL individuals (age 54+12 y, 70% women, Clinical Dementia Rating=0, MMSE27, neuropsychological test performance within norms by age and education) with complete dietary information and cross-sectional, 3D T1-weighted Magnetic Resonance Imaging (MRI; gray matter volumes, GMV, a marker of brain atrophy), 11C-Pittsburgh compound-B (PiB; a marker of fibrillar amyloid-β, Aβ) and 18F-fluorodeoxyglucose (FDG; a marker of glucose metabolism, METglc) Positron Emission Tomography (PET) scans were examined.Dietary intake of 35 nutrients associated with cognitive function and AD was assessed using the Harvard/Willet Food Frequency Questionnaire. Principal component analysis was used to generate nutrient patterns (NP) from the full nutrient panel. Statistical parametric mapping and voxel based morphometry were used to assess the associations of the identified NPs with AD biomarkers.None of the participants were diabetics, smokers, or met criteria for obesity. Five NPs were identified: NP1 was characterized by most B-vitamins and several minerals [VitB and Minerals]; NP2 by monounsaturated and polyunsaturated fats, including ω-3 and ω-6 PUFA, and vitamin E [VitE and PUFA]; NP3 by vitamin A, vitamin C, carotenoids and dietary fibers [Anti-oxidants and Fibers]; NP4 by vitamin B12, vitamin D and zinc [VitB12 and D]; NP5 by saturated, trans-saturated fats, cholesterol and sodium [Fats]. Voxel-based analysis showed that NP4 scores [VitB12 and D] were positively associated with METglc and GMV, and negatively associated with PiB retention in AD-vulnerable regions (p0.001). In addition, both METglc and GMV were positively associated with NP2 scores [VitE and PUFA], and negatively associated with NP5 scores [Fats] (p0.001), and METglc was positively associated with higher NP3 scores [Anti-oxidants and Fibers] (p0.001). Adjusting for age, gender, ethnicity, education, caloric intake, BMI, alcohol consumption, family history and Apolipoprotein E (APOE) status did not attenuate these relationships. The identified 'AD-protective' nutrient combination was associated with higher intake of fresh fruit and vegetables, whole grains, fish and low-fat dairies, and lower intake of sweets, fried potatoes, high-fat dairies, processed meat and butter.Specific dietary NPs are associated with brain biomarkers of AD in NL individuals, suggesting that dietary interventions may play a role in the prevention of AD by modulating AD-risk through its effects on Aβ and associated neuronal impairment.

Brain 18F-fluorodeoxyglucose (18F-FDG) PET allows the in vivo study of cerebral glucose metabolism, reflecting neuronal and synaptic activity. 18F-FDG-PET has been extensively used to detect metabolic alterations in several neurologic diseases compared with normal aging. However, healthy subjects have variants of 18F-FDG distribution, especially as associated with aging. This article focuses on 18F-FDG-PET findings in so-called normal brain aging, and in particular on metabolic differences occurring with aging and as a function of people’s gender. The effect of different substances, medications, and therapy procedures are discussed, as well as common artifacts.

Positron emission tomography (PET) of brain amyloid is a technology that has been approved by Food and Drug Administration and European Medical Agency, but its clinical utility in medical practice requires careful definition. To provide guidance to italian dementia care practitioners, patients, and caregivers, a group of experts from “Associazione Italiana di Medicina Nucleare” (AIMN), “Associazione Italiana di Psicogeriatria” (AIP) and “Societa Italiana per lo Studio delle Demenze” (SINDEM) convened the Italian Interdisciplinary Working Group on Amyloid Imaging. The Working Group considered a range of clinical scenarios in which amyloid PET should be recommended. Peer-reviewed, published literature was searched to ascertain available evidence relevant to these recommendations. Although empirical evidence of impact on clinical outcomes is not yet available, a set of specific recommended use criteria were agreed to define the types of patients and clinical circumstances in which amyloid PET could be used. Both correct and incorrect uses were considered and formulated. Because both dementia care and amyloid-PET technology are in active development, these recommendations will require periodic reassessment.

Experimental studies suggest that doxycycline attenuates post-infarction remodelling and exerts protective effects on myocardial ischaemia/reperfusion injury. However, the effects of the drug in the clinical setting are unknown. The aim of this study was to examine the effect of doxycycline on left ventricular (LV) remodelling in patients with acute ST-segment elevation myocardial infarction (STEMI) and LV dysfunction.Open-label, randomized, phase II trial. Immediately after primary percutaneous coronary intervention, patients with STEMI and LV ejection fraction40% were randomly assigned to doxycycline (100 mg b.i.d. for 7 days) in addition to standard therapy, or to standard care. The echo LV end-diastolic volumes index (LVEDVi) was determined at baseline and 6 months. (99m)Tc-Sestamibi-single-photon emission computed tomography infarct size and severity were assessed at 6 months. We calculated a sample size of 110 patients, assuming that doxycycline may reduce the increase in the LVEDVi from baseline to 6 months50% compared with the standard therapy (statistical power80% with a type I error = 0.05). The 6-month changes in %LVEDVi were significant smaller in the doxycycline group than in the control group [0.4% (IQR: -16.0 to 14.2%) vs.13.4% (IQR: -7.9 to 29.3%); P = 0.012], as well as infarct size [5.5% (IQR: 0 to 18.8%) vs. 10.4% (IQR: 0.3 to 29.9%) P = 0.052], and infarct severity [0.53 (IQR: 0.43-0.62) vs. 0.44 (IQR: 0.29-0.60), P = 0.014], respectively.In patients with acute STEMI and LV dysfunction, doxycycline reduces the adverse LV remodelling for comparable definite myocardial infarct size (NCT00469261).

Quantitative maps of the cerebral metabolic rate of glucose (CMRGlc) derived from 2-18F-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography (PET) images are useful in brain studies, but practical methods are needed to allow their use in clinical routine. This review looks at the kinetic model at the basis of absolute quantification of CMRGlc and at the main methods for measuring CMRGlc using 18F-FDG PET, also focusing on some critical steps in the procedure.

The goal of this study is to determine the technical accuracy of segmental perfusion parameters assessed with quantitative cardiac PET imaging in the evaluation of coronary artery disease (CAD) in patients with stable angina. A cohort of patients who participated in the EVINCI protocol underwent an evaluation of coronary anatomy by invasive coronary angiography (ICA) and/or coronary computed tomography angiography (CCTA) and PET myocardial perfusion imaging with H2 15O, 13NH3 or 82Rb. PET studies were analyzed by two independent observers blinded to clinical and instrumental data, and classified as positive or negative for significant CAD using only segmental perfusion measurements and cut-off values from literature. On a per-patient basis, the overall inter-observer agreement on PET results was 90 % (kappa = 0.79), indicating substantial agreement. On a per-vessel basis, the inter-observer agreement on PET results was 88 % (kappa = 0.74) in the RCA territory, 94 % (kappa = 0.84) in the LAD territory and 94 % (kappa = 0.85) in the LCX territory. Segmental PET measurements correctly identified 85 % of the patients, resulting in a global sensitivity of 86 %, a specificity of 84 %, a positive predictive value (PPV) of 69 % and a negative predictive value (NPV) of 93 %. In vessel-based analyses, quantitative perfusion parameters had a sensitivity, specificity, PPV and NPV of 92 %, 82 %, 42 % and 99 %, respectively, for the detection of significant coronary stenoses in all major coronary arteries. The assessment of absolute myocardial perfusion parameters measured at a segment level lead to reliable and accurate identification of patients with significant coronary stenosis at ICA and/or CCTA.

The purpose of this study was to evaluate the potential usefulness of [18F]-Choline PET/CT in the restaging of prostate cancer patients, who presented a rising PSA.We evaluated 170 prostate cancer patients, previously radically treated, that were referred for restaging with [18F]-Choline PET/CT.A total of 129 patients (median PSA 4.29 ng/ml at relapse) showed one or more areas of high uptake on PET/CT scan, while 41 patients with a median PSA of 1.07 ng/ml at relapse showed negative PET/CT scans. No false negative was found, while 31 patients were identified as false positive. Specificity of Choline PET/CT in our series was 56.9 %, while sensibility was 100 %. At the time of restaging, a PSA value superior or equal to 1 ng/ml was found to be a statistically significant predictive factor of PET positivity, either at the univariate (p0.0001) and at the multivariate analysis (p0.0001).Based on our findings, [18F]-Choline PET/CT is confirmed as a useful diagnostic tool to detect early recurrence, in patients with increasing PSA after primary treatment. However, in case of a mild increase in PSA, positive results must be validated with other techniques, as specificity and positive predictive value of [18F]-Choline PET/CT decrease with the lower values of PSA.

Clinical use of positron emission tomography (PET) is now well established in neurodegenerative disorders, especially in the diagnosis of dementia. Measurement of cerebral glucose metabolism is of significant value, and it facilitates early diagnosis, appropriate differential diagnosis, and the evaluation of drug treatment in patients with dementia. In addition, tracers offer new perspectives for studying the neuropathology of underlying dementia, such as the accumulation of amyloid proteins, tau-proteins, or the presence of neuroinflammation. Finally, PET tracer studies of different neurotransmitter systems in dementia may not only increase the understanding of pathophysiologic mechanisms of the different disorders, but also improve diagnostic accuracy. In conclusion, PET imaging with different tracers offers reliable biomarkers in dementia, which can assist clinicians in the diagnosis of different dementing disorders, especially in the situation of overlapping phenotypes.

Objective: To verify whether features of CNS involvement can be detected in SLE patients without overt neuropsychiatric manifestations.Methods: 114 SLE patients who had never received a diagnosis of neuropsychiatric lupus (never NPSLE) were studied and compared to 65 SLE patients with known neuropsychiatric involvement (NPSLE). The study relied on evaluation of neurocognitive functions by means of a battery of neuropsychological tests, on psychiatric and neuropsychological assessments and on neuroimaging studies (computed tomography, magnetic resonance, single photon emission computed tomography (SPECT)).Results: Clinical features, including disease duration/activity and pharmacological therapy, of never-NPSLE and NPSLE patients were similar. Short-term and long-term memory, visuo-spatial and verbal information processing were similarly compromised in never-NPSLE and in NPSLE patients; only attention was significantly more compromised in NPSLE patients. Psychiatric morbidity was higher than expected in never-NPSLE patients, although less than in the control neuropsychiatric group. Ischemic lesions, multiple small high intensity lesions and cortical atrophy, detected by CT and MR scans, as well as abnormal SPECT were also frequently detected in never NPSLE patients. Interestingly, left parietal and occipital area hypoperfusion by SPECT was significantly more frequent in the patients with impaired visuo-spatial intelligence and short-term memory.Conclusions: Most abnormalities detected by available diagnostic tools and characteristics of neuropsychiatric SLE are also present in non-symptomatic patients. They may derive from an unexpected widespread involvement of the CNS and are not per se sufficient, in the absence of clinical manifestations, for a diagnosis of neuropsychiatric SLE.

Because of persistent stunning, post-treatment functional abnormalities could identify the initial risk area. The study aims to detect myocardial salvage using post-revascularization gated SPECT in acute myocardial infarction (AMI) treated by reperfusion therapy.In 36 AMI patients, we performed a first gated SPECT injecting (99m)Tc-sestamibi before primary percutaneous coronary intervention (PCI), and a second 5 days later. The salvage index defined by the two perfusion images was compared with the value obtained by subtracting in the second gated SPECT the extent of perfusion defect from the extent of wall thickening abnormalities.The wall thickening salvage index correlated with the reference perfusion salvage index (Spearman's ρ = .92, P .0001), with a 95% limit of agreement = ±.25. The agreement between the classifications in salvage index tertiles of the reference and of the wall thickening salvage index was good (kappa = .75). All patients with optimal PCI result and 18/24 of those with intermediate or poor outcome were correctly classified.Comparing function and perfusion in a single post-PCI (99m)Tc-sestamibi gated SPECT it is possible to estimate myocardial salvage. This could have useful implications in studies comparing different treatment strategies for AMI.

Perfusion gated single photon emission computed tomography (SPECT) can assess with good reproducibility left ventricular (LV) volumes and ejection fraction (EF). Whether this reproducibility is maintained in long-term follow-up is unknown.We compared LV end-diastolic (ED) and end-systolic (ES) volumes (V) as well as EF calculated using gated SPECT and QGS software in 103 coronary artery disease patients studied twice at1-year interval because of standard clinical indications. Patients were divided into two groups: (A) 67 patients without major clinical changes and with stable resting perfusion and (B) 36 with modified clinical status or resting perfusion.The relationship between gated SPECT 2 EF (=y) and gated SPECT 1 EF (=x) was for group A: y=0.91 x + 5.34, r=0.92, p0.0001, SEE=4 and for group B: y=0.67 x + 13.6, r=0.63, p0.0001, SEE=10. The 95% limit of agreement was 8 EF units for group A and 20.6 EF units for group B. For EDV, the 95% limit of agreement was 22 ml for group A and 52 ml for group B. For ESV, the 95% limit of agreement was 13 ml for group A and 44 ml for group B.In stable patients with an unmodified resting perfusion pattern the functional parameters derived from perfusion gated SPECT have good reproducibility even after a prolonged time interval. This supports the value of gated SPECT for serial evaluations of LV function.

Female sex and advanced age have adverse prognostic meaning in acute myocardial infarction. Whether gender and/or age influence the relationship between infarct size, infarct severity, and left ventricular ejection fraction (LVEF) is unclear. We examined 460 patients (359 men) with acute myocardial infarction submitted to successful primary percutaneous coronary intervention. Infarct size, infarct severity, and LVEF were evaluated with perfusion gated SPECT at one month of index infarction. There were no significant correlations between age and infarct size or infarct severity, and between age and LVEF. Moreover, elderly age (≥75 years) did not influence the relationship between LVEF and infarct size or infarct severity. Conversely, there was a significant gender-related difference in the relationship between LVEF and infarct size (F = 20.5, P

Persistent abnormalities are usually not detected in patients with Takotsubo cardiomyopathy (TTC). Since sympathetically mediated myocardial damage has been proposed as a causative mechanism of TTC, we explored whether mental stress could evoke abnormalities in these patients.One month after an acute event, 22 patients fulfilling all TTC diagnostic criteria and 11 controls underwent resting and mental stress gated single photon emission computed tomography (SPECT). Perfusion, wall motion, transient ischaemic dilation (TID) and left ventricular (LV) ejection fraction (EF) were evaluated.None of the controls showed stress-induced abnormalities. Mental stress evoked regional changes (perfusion defects and/or wall motion abnormality) in 16 TTC subjects and global abnormalities (LVEF fall5% and/or TID1.10) in 13; 3 had a completely negative response. TID, delta LVEF and delta wall motion score were significantly different in TTC vs control patients: 1.08 + or - 0.20 vs 0.95 + or - 0.11 (p0.05), -1.7 + or - 6% vs 4 + or - 5% (p0.02) and 2.5 (0, 4.25) vs 0 (0, 0) (p0.002), respectively.Mental stress may evoke regional and/or global abnormalities in most TTC patients. The abnormal response to mental stress supports the role of sympathetic stimulation in TTC. Mental stress could thus be helpful for TTC evaluation.

The aim of the present study was to evaluate the reciprocal relationships between motor impairment, dopaminergic dysfunction, and cerebral metabolism (rCMRglc) in de novo Parkinson's disease (PD) patients.Twenty-six de novo untreated PD patients were scanned with (123)I-FP-CIT SPECT and (18)F-FDG PET. The dopaminergic impairment was measured with putaminal (123)I-FP-CIT binding potential (BP), estimated with two different techniques: an iterative reconstruction algorithm (BP(OSEM)) and the least-squares (LS) method (BP(LS)). Statistical parametric mapping (SPM) multiple regression analyses were performed to determine the specific brain regions in which UPDRS III scores and putaminal BP values correlated with rCMRglc.The SPM results showed a negative correlation between UPDRS III and rCMRglc in premotor cortex, and a positive correlation between BP(OSEM) and rCMRglc in premotor and dorsolateral prefrontal cortex, not surviving at multiple comparison correction. Instead, there was a positive significant correlation between putaminal BP(LS) and rCMRglc in premotor, dorsolateral prefrontal, anterior prefrontal, and orbitofrontal cortex (p0.05, corrected for multiple comparison).Putaminal BP(LS) is an efficient parameter for exploring the correlations between PD severity and rCMRglc cortical changes. The correlation between dopaminergic degeneration and rCMRglc in several prefrontal regions likely represents the cortical functional correlate of the dysfunction in the motor basal ganglia-cortical circuit in PD. This finding suggests focusing on the metabolic course of these areas to follow PD progression and to analyze treatment effects.

Background. The relationship among plasma brain natriuretic peptide (BNP), markers of extracellular matrix (ECM) remodeling, and left ventricular (LV) dilation after reperfused acute myocardial infarction is poorly known. Methods and Results. Echocardiogram, plasma BNP, and ECM degradation markers (serum amino-terminal telopeptide of type I procollagen and type III procollagen and carboxy-terminal telopeptide of type I procollagen [ICTP]) were evaluated in 34 patients at days 1, 3, and 30 after first reperfused acute myocardial infarction. At 1 month, infarct size and severity and LV volume were measured by sestamibi gated single photon emission computed tomography. Patients were stratified according to day 3 BNP levels into 2 groups: group 1 (n=17) had BNP values over the median value, and group 2 (n=17) had BNP values under the median value. Infarct size and severity were similar in the 2 groups. LV volumes increased in group 1 but decreased in group 2 (P

The aim of this study was to evaluate the accuracy of different single-photon emission computed tomography (SPECT) reconstruction techniques in measuring striatal N-omega-fluoropropyl-2beta-carbomethoxy-3beta-4-[(123)I]iodophenyl-nortropane ((123)I-FP-CIT) binding in de novo Parkinson's disease (PD) patients, in order to find a correlation with clinical scales of disease severity in the initial phases of disease.Thirty-six de novo PD patients underwent (123)I-FP-CIT SPECT and MRI scan. SPECT data were reconstructed with filtered back projection (FBP), with an iterative algorithm (ordered subset expected maximization, OSEM) and with a method previously developed in our institution, called least-squares (LS) method. The ratio of specific to non-specific striatal (123)I-FP-CIT binding (binding potential, BP) was used as the outcome measure with all the reconstruction methods (BP(FBP), BP(OSEM), BP(LS)).The range of values of striatal BP(LS) was significantly greater than BP(FBP) and BP(OSEM). For all striatal regions, estimates of BP(FBP) correlated well with BP(OSEM) (r = 0.84) and with BP(LS) (r = 0.64); BP(OSEM) correlated significantly with BP(LS) (r = 0.76). A good correlation was found between putaminal BP(LS) and Hoen and Yahr, Unified PD Rating Scale (UPDRS) and lateralized UPDRS motor scores (r = -0.46, r = -0.42, r = -0.39, respectively). Neither putaminal BP(FBP) nor putaminal BP(OSEM) correlated with any of these motor scores.In de novo PD patients, (123)I-FP-CIT BP values derived from FBP and OSEM reconstruction techniques do not permit to differentiate PD severity. The LS method instead finds a correlation between striatal BP and disease severity scores. The results of this study support the use of (123)I-FP-CIT BP values estimated with the LS method as a biomarker of PD severity.

This multicenter study examined (18)F-FDG PET measures in the differential diagnosis of Alzheimer's disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB) from normal aging and from each other and the relation of disease-specific patterns to mild cognitive impairment (MCI).We examined the (18)F-FDG PET scans of 548 subjects, including 110 healthy elderly individuals ("normals" or NLs), 114 MCI, 199 AD, 98 FTD, and 27 DLB patients, collected at 7 participating centers. Individual PET scans were Z scored using automated voxel-based comparison with generation of disease-specific patterns of cortical and hippocampal (18)F-FDG uptake that were then applied to characterize MCI.Standardized disease-specific PET patterns were developed that correctly classified 95% AD, 92% DLB, 94% FTD, and 94% NL. MCI patients showed primarily posterior cingulate cortex and hippocampal hypometabolism (81%), whereas neocortical abnormalities varied according to neuropsychological profiles. An AD PET pattern was observed in 79% MCI with deficits in multiple cognitive domains and 31% amnesic MCI. (18)F-FDG PET heterogeneity in MCI with nonmemory deficits ranged from absent hypometabolism to FTD and DLB PET patterns.Standardized automated analysis of (18)F-FDG PET scans may provide an objective and sensitive support to the clinical diagnosis in early dementia.

The normative reference sample is crucial for the diagnosis of Alzheimer9s disease (AD) with automated 18F-FDG PET analysis. We tested whether an 18F-FDG PET database of longitudinally confirmed healthy elderly individuals (“normals,” or NLs) would improve diagnosis of AD and mild cognitive impairment (MCI). Methods: Two 18F-FDG PET databases of 55 NLs with 4-y clinical follow-up examinations were created: one of NLs who remained NL, and the other including a fraction of NLs who declined to MCI at follow-up. Each 18F-FDG PET scan of 19 NLs, 37 MCI patients, and 33 AD patients was z scored using automated voxel-based comparison to both databases and examined for AD-related abnormalities. Results: Our database of longitudinally confirmed NLs yielded 1.4- to 2-fold higher z scores than did the mixed database in detecting 18F-FDG PET abnormalities in both the MCI and the AD groups. 18F-FDG PET diagnosis using the longitudinal NL database identified 100% NLs, 100% MCI patients, and 100% AD patients, which was significantly more accurate for MCI patients than with the mixed database (100% NLs, 68% MCI patients, and 94% AD patients identified). Conclusion: Our longitudinally confirmed NL database constitutes reliable 18F-FDG PET normative values for MCI and AD.

The aim of this follow-up study was to assess persistent motor and regional cerebral blood flow (rCBF) changes in patients with Parkinson's disease (PD) treated with high-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN).Ten PD patients with STN-DBS underwent three rCBF SPECT studies at rest, once preoperatively in the off-drug condition (T(0)), and twice postoperatively in the off-drug/off-stimulation conditions at 5 +/- 2 (T(1)) and 42 +/- 7 months (T(2)). Patients were assessed using the UPDRS, HY and SE scales. SPM was used to investigate baseline rCBF changes from the preoperative condition to the postoperative conditions and the relationship between rCBF and UPDRS scores used as covariate of interest.Parkinsonian patients showed a clinical improvement which was significant only on follow-up at 42 months. The main effect of treatment from T(0) to T(1) was to produce baseline rCBF increases in the pre-supplementary motor area (pre-SMA), premotor cortex and somatosensory association cortex. From T(1) to T(2) a further baseline rCBF increase was detected in the pre-SMA (p0.0001). A correlation was detected between the slight improvement in motor scores and the rCBF increase in the pre-SMA (p0.0001), which is known to play a crucial role in clinical progression.Our study suggests the presence of adaptive functional changes in the human brain of PD patients treated with long-term STN-DBS. Such adaptive processes seem to occur in the pre-SMA and to play only a slightly beneficial role in terms of functional compensation of motor impairment.

The extraordinary success of imatinib in gastrointestinal stromal tumor (GIST) represents a model for molecularly targeted therapy of solid tumors. Research is currently going to identify the molecular basis of mechanisms of action and drug resistance. For the optimal management of the patients treated, a multidisciplinary approach, including medical oncologists, surgeons, pathologists, and radiologists is needed. In this article, we reviewed recent advances in the clinical management of GIST patients treated with imatinib, and in the knowledge of the molecular mechanisms that are basic to imatinib effects.

Purpose/objective(s) Due to its anti-inflammatory, antifibrotic and antineoplastic properties, the PPAR-γ agonist rosiglitazone is of interest in the prevention and therapy of radiation-induced pulmonary injury. We evaluated the radioprotective effects of rosiglitazone in a murine model of pulmonary damage to determine whether radioprotection was selective for normal and tumor tissues. Methods Lungs in C57BL/6J mice were irradiated (19 Gy) with or without rosiglitazone (RGZ, 5 mg/kg/day for 16 weeks, oral gavage). Computed tomography (CT) was performed and Hounsfield Units (HU) were determined during the observation period. Histological analysis and evaluation of fibrosis/inflammatory markers by western blot were performed at 16 weeks. A549 tumor-bearing CD1 mice were irradiated (16 Gy) with or without RGZ, and tumor volumes were measured at 35 days. Results Rosiglitazone reduced radiologic and histologic signs of fibrosis, inflammatory infiltrate, alterations to alveolar structures, and HU lung density that was increased due to irradiation. RGZ treatment also significantly decreased Col1, NF-kB and TGF-β expression and increased Bcl-2 protein expression compared to the irradiation group and reduced A549 clonogenic survival and xenograft tumor growth. Conclusions Rosiglitazone exerted a protective effect on normal tissues in radiation-induced pulmonary injury, while irradiated lung cancer cells were not protected in vivo and in vitro. Thus, rosiglitazone could be proposed as a radioprotective agent in the treatment of lung cancer.

ST-segment resolution is used to classify the response to reperfusion therapy in acute myocardial infarction, but the possibility to predict outcome in individual patients is unclear, particularly in the setting of primary percutaneous coronary intervention (PCI) and abciximab therapy. We studied 213 patients who underwent successful revascularization with PCI. Maximal ST-segment elevation was measured before and 30 minutes after PCI. Patient outcome was defined on the basis of infarct size and left ventricular ejection fraction (EF) as derived from gated single-photon emission computed tomography that was acquired 1 month after infarction. Patients who hador =50% ST resolution showed a smaller infarct (15.1 +/- 13.6% vs 19.9 +/- 15.7%, p0.05) but not a higher left ventricular EF (48.7 +/- 12.3% vs 45.2 +/- 11.8%) than did patients who had50% resolution. According to cluster analysis of infarct size and left ventricular EF, 132 patients had favorable outcome (central values: infarct size 7.5%, left ventricular EF 55%) and 81 did not (central values: infarct size 30%, left ventricular EF 36%). Using receiver-operating characteristic curve analysis, the optimal ST-resolution cutoff was60%, with 77% sensitivity and 51% specificity for predicting favorable outcome. ST-segment elevationor =4.5 mV before PCI was 80% sensitive and 48% specific, and ST-segment elevationor =1 mV after PCI was 74% sensitive and 60% specific for predicting favorable outcome. In conclusion, in the setting of primary PCI and abciximab therapy, ST-segment elevation resolution requires a high threshold (60%) to effectively classify patients; the capability of ST-segment analysis to predict patient outcome is limited, with ST-segment elevation after PCI showing the best compromise between sensitivity and specificity.

Despite investments carried out in the research since Alzheimer's disease (AD) was firstly defined as an isolated clinical entity, there is still a lack of appropriate cure and effective therapies to halt or slow the disease progression. While fundamental research has provided a better characterization of AD, much remains to be done for the development of new biological treatment strategies. It is now being debated whether functional neuroimaging (FNI) could help improve diagnostic accuracy and become a possible biomarker of AD. The primary purpose of this review was to determine whether data already published in the literature meet formal technology assessment standards for using regional cerebral blood flow (rCBF) or glucose metabolism (rCMRGlu) as a biomarker for AD. The secondary purpose was to identify any remaining gaps that might need to be systematically addressed before drug developers and regulators accept FNI as a biomarker for AD. The present paper reviews the literature regarding metabolic positron emission tomography (PET) and perfusion single photon emission computed tomography (SPECT) studies in AD. There is evidence that treatment with acetylcholinesterase inhibitors (AChEI) leads to changes in brain physiology within the brain regions critical to AD pathology, i.e. the temporal, parietal and frontal association cortex. However, a thorough analysis combining functional and neuropsychological data has not yet been attempted, and much research is needed to validate the role of FNI as a surrogate endpoint for AD clinical trials.

Background. Reflux nephropathy (RN) is a pathophysiological human model of reduced nephron reserve, due to loss of renal mass, but little information exists about the role of urinary endothelin-1 (uET-1) in this disease. The aim of this study was to assess the presence of uET-1-like-immunoreactivity (uET-1L) in RN patients, particularly if lateralized renal damage existed. Methods. Thirty patients with vescico-ureteral reflux (VUR) and consequent RN, were studied. The presence of VUR was established by voiding cysto-urethrography. RN was assessed and graded by 99mTc-dimercapto-succinic acid scan (DMSA). Renal plasma flow (ERPF) was evaluated by 123 I-Hippuran renal sequential scintigraphy, and glomerular filtration rate (GFR) by creatinine clearance. Forty-five healthy subjects were selected as a control group. uET-lL excretion, in both affected and control groups, was assayed. Results. Mann Whitney U test showed a significant difference between control and patient groups in both GFR and uET-1L. A good correlation between DMSA grading, single kidney clearance and VUR grade was shown. A significant relationship was also shown between uET-1L and both ERPF and GFR. Patients with RN were divided into two subgroups according to functional damage lateralization. Between the two groups, a significant difference was found only for uET-1L when GFR was applied as a covariate in ANCOVA analysis. Conclusion. Our preliminary results confirmed the increase of urinary ET-1L excretion in RN, especially when renal functional injury was lateralized.

Purpose: After acute myocardial infarction (AMI), left ventricular (LV) remodelling may occur despite successful reperfusion. This study aimed to investigate by gated single photon emission computed tomography (SPECT) the long-term evolution of myocardial perfusion and LV function after AMI and to identify the predictors of LV remodelling. Methods: Sixty-eight AMI patients successfully treated by primary percutaneous coronary intervention underwent 99mTc-sestamibi gated SPECT at 1 month (baseline) and over 6-month follow-up after the acute event. LV remodelling was defined as 20% increase in LV end-diastolic volume at follow-up. Results: At baseline, patients with remodelling (n=14) showed larger (infarct size 29.3±7.8%) and more transmural (infarct severity 0.28±0.10) infarctions, and reduced LV ejection fraction (35.4±5.6%), but similar LV volume indexes, compared to patients without remodelling (n=54) (infarct size 20.8±14.4%, p

Atrial fibrillation (AF) and coronary microvascular dysfunction (CMD) are common in hypertrophic cardiomyopathy (HCM), but whether they are associated is unclear. We assessed the relationship between AF and CMD in HCM. Global hyperemic myocardial blood flow (hMBF) was measured in 95 HCM patients (16 with, 79 without paroxysmal or chronic AF) by N-13 ammonia positron emission tomography (PET) after dipyridamole infusion. AF patients were older (50.5 ± 13.4 vs. 38.7 ± 14.9 years, P