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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.

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.

The neuropathological processes eventually leading to Alzheimer's disease (AD) are thought to start decades before the appearance of clinical symptoms and the clinical diagnosis of AD dementia. The term "preclinical AD" has been recently introduced to identify this "silent stage" of AD, when the disease is already present, but symptoms are not yet clinically evident. Advances in AD biomarkers have dramatically improved the ability to detect AD pathological processes in vivo in cognitively intact subjects, thus demonstrating the presence of AD pathology in the preclinical phase. This review focuses on the recent advances in the field of neuroimaging and CSF AD biomarkers specifically in the preclinical phase of AD, and aims to discuss the significance that such biomarkers could have in cognitively intact subjects. Even though the use of such biomarkers in AD preclinical phase has contributed to improve our understanding of AD early pathological processes, it raised also a number of new challenges that still remain to be overcome, such as a better definition of the clinical and individual significance of currently known biomarkers in preclinical stages and the development of novel biomarkers of different early AD-related events.

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.

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).

In recent years, many efforts have been addressed to the development of new imaging techniques enabling early diagnosis and non-invasive monitoring of primary tumors and metastases. Among the integrin family, αVβ3 and α5β1 receptors have been characterized as prototypic markers of angiogenic tumor-associated endothelial cells and their overexpression in tumor cells has been correlated with the progression of various tumor types such as melanoma. Herein, we report the synthesis, characterization and preclinical evaluation of an 111In-labelled DOTA conjugate embodying a cyclic aminoproline-RGD-peptide motif as a competent αVβ3 integrin ligand, to be used as a radiotracer in preclinical models of human melanoma. Practical and efficient chemical and radiochemical synthetic procedures were set up, the in vitro stability and hydrophilicity of a cold c(AmpRGD)-DOTA conjugate were demonstrated, the binding affinities toward isolated αVβ3/α5β1 receptors were assayed and inhibition of cell adhesion to vitronectin and fibronectin was tested in human melanoma and endothelial progenitor cell lines. The anti-angiogenic activity of the peptide conjugates was also tested and assessed in vitro by tubulogenesis assays. The in vivo biodistribution SPECT/CT studies in healthy mice revealed high renal uptake at earlier observation times (30 min to 4 h p.i.) and complete clearance from the kidney at 48 h p.i.; the displacement experiments in human melanoma xenografts confirmed the αVβ3/α5β1 integrin specificity of tumor uptake, suggesting the 111In-labelled c(AmpRGD)-DOTA bioconjugate as a promising starting point in the search for new SPECT-imaging small-molecular probes for non-invasive visualization of tumor angiogenesis, human melanoma and other αVβ3/α5β1-positive tumors.

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

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).

BackgroundBody image distortion is a core symptom of eating disorders. Functional magnetic resonance imaging (fMRI) studies on body image processing, described different patterns of neural response, mainly involving the inferior and superior parietal lobules, and the dorsolateral prefrontal cortex (DLPFC), with conflicting results.MethodsThe neural response to the view of their own body pictures (normal size and distorted) was evaluated in 18 female anorexia nervosa (AN) restricting type patients, and in 19 healthy female subjects (HC) using fMRI. Clinical assessment was performed by means of the structured clinical interview for DSM-IV and self-reported questionnaires.ResultsIn response to the body image distortion, patients and controls showed an inverse pattern of activation, with the widest extent of activation in the oversize condition in AN, while in the undersize condition in HC. AN and HC showed a similar pattern of neural response to the view of their own body, with an increased activation in the extrastriate body area, superior and inferior parietal lobule and prefrontal areas, although the extent of activation in HC was more limited as compared with AN patients. Increased activity in AN patients, compared with HC, was observed in the DLPFC in response to the oversized body picture and a significant correlation was found in AN patients between DLPFC activation and eating disorder psychopathology.ConclusionsOur findings suggest the existence of a continuum from normalcy to pathology in neural response to body image, and confirm the clinical relevance of body image distortion in AN, reinforcing the key role of attentive, executive and self-evaluation networks in AN visual processing of own distorted body image.

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.

The development of prevention therapies for Alzheimer's disease (AD) would greatly benefit from biomarkers that are sensitive to subtle brain changes occurring in the preclinical stage of the disease. Early diagnostics is necessary to identify and treat at risk individuals before irreversible neuronal loss occurs. In vivo imaging has long been used to evaluate brain structural and functional abnormalities as predictors of future AD in non-demented persons. Prior to development of amyloid-beta (Abeta) tracers for positron emission tomography (PET), the most widely utilized PET tracer in AD was 2-[18F]fluoro-2-Deoxy-D-glucose (FDG) PET. For over 20 years, FDG-PET has been used to measure cerebral metabolic rates of glucose (CMRglc), a proxy for neuronal activity, in AD. Many studies have shown that CMRglc reductions occur early in AD, correlate with disease progression, and predict histopathological diagnosis. This paper reviews reports of clinical and preclinical CMRglc reductions observed in association with genetic and non-genetic risk factors for AD. We then briefly review brain Abeta PET imaging studies in AD and discuss the potential of combining symptoms-sensitive FDG-PET measures with pathology-specific Abeta-PET to improve the early detection of AD.

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

One of the main features of Alzheimer's disease (AD) is the severe reduction of the cerebral metabolic rate for glucose (CMRglc). In vivo imaging using positron emission tomography with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG-PET) demonstrates consistent and progressive CMRglc reductions in AD patients, the extent and topography of which correlate with symptom severity. Increasing evidence suggests that CMRglc reductions occur at the preclinical stages of AD. CMRglc reductions were observed on FDG-PET before the onset of disease in several groups of at-risk individuals, including patients with mild cognitive impairment (MCI), often a prodrome to AD; presymptomatic individuals carrying mutations responsible for early-onset familial AD; cognitively normal elderly individuals followed for several years until they declined to MCI and eventually to AD; normal, middle-aged individuals who expressed subjective memory complaints and were carriers of the apolipoprotein E epsilon-4 allele, a strong genetic risk factor for late-onset AD. However, the causes of the early metabolic dysfunction forerunning the onset of AD are not known. An increasing body of evidence indicates a deficient or altered energy metabolism that could change the overall oxidative microenvironment for neurons during the pathogenesis and progression of AD, leading to alterations in mitochondrial enzymes and in glucose metabolism in AD brain tissue. The present paper reviews findings that implicate hypometabolism and oxidative stress as crucial players in the initiation and progression of synaptic pathology in AD.

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

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.

This study was designed to examine the correlations between resting-state brain glucose metabolism (CMRglc), as measured with Positron Emission Tomography and performance on executive function tasks in Alzheimer's disease (AD), while taking into account the severity of cognitive deterioration. We addressed this issue in 50 AD patients, classified as very mild (n = 22) and mild (n = 28) AD on the basis of an extensive neuropsychological battery. Thirteen healthy subjects were selected as controls for the neuropsychological measures. Statistical Parametric Mapping (SPM) was used to examine voxel-wise correlations between CMRglc and scores on selected cognitive tests of executive functions: the Stroop Test, the Trail Making Test, the Dual Task and the Phonemic Fluency, while correcting for age and global CMRglc. All analyses were done separately for the two AD subgroups. The very mild AD patients showed significant associations between Stroop and Trail Making Test scores and prefrontal regions metabolism, whereas the mild AD patients exhibited more widely distributed cognitive-metabolic correlations extending to the posterior brain regions. These data suggest that a large cortical network is implicated in executive dysfunction in AD, and that the pattern of cognitive-metabolic correlations varies according to disease severity.

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: Clinically apparent Alzheimer's disease (AD) is thought to result when brain tissue damage exceeds a critical threshold of "brain reserve", a process possibly accelerated by the apolipoprotein E (ApoE) E4 allele. The interaction between onset age and ApoE genotype was investigated to assess whether early disease onset (

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.

Declines in brain glucose metabolism have been described early in Alzheimer's disease (AD), and there is evidence that a genetic predisposition to AD contributes to accelerate this process. The epsilon 4 (e4) allele of the apolipoprotein E (ApoE) gene has been implicated as a major risk factor in this process. The aim of this FDG-PET study was to assess the ApoE e4 dose related effect on regional cerebral glucose metabolism (METglc) in clinical AD patients, with statistical voxel based methods.Eighty six consecutive mild to moderate AD patients included in the Network for Efficiency and Standardisation of Dementia Diagnosis database underwent FDG-PET scans at rest. PCR was used to determine the ApoE genotype. Patients were grouped as e4 non-carriers (n = 46), e3/e4 (n = 27) and e4/e4 (n = 13) carriers. A voxel-based mapping program was used to compare each AD subgroup with a database of 35 sex and age matched controls (p0.001, corrected for cluster extent) and also to compare between the subgroups (p0.001, uncorrected).No difference was found as to age at examination, age at onset, sex, disease duration, educational level, or severity of dementia between AD subgroups. Compared with controls, all AD subgroups had equivalent METglc reductions in the precuneus, posterior cingulate, parietotemporal, and frontal regions. Direct comparisons between AD subgroups indicated that patients with at least one e4 allele had METglc reductions within additional associative and limbic areas compared with e4 non-carriers.The present FDG-PET study showed different metabolic phenotypes related to the ApoE genotype in clinical AD patients, as revealed with voxel based statistical methods. The results suggest a generalised disorder in e4 carriers impairing metabolism globally, in addition to the more localised changes typical of AD patients.

Previous positron emission tomography (PET) studies with fluorodeoxglucose (FDG) as tracer in healthy elders showed that the epsilon4 allele of the apolipoprotein E (ApoE) gene is disruptive to cerebral glucose metabolism (rCMRglu), possibly through the interaction with the aging process. The present study was aimed at assessing whether this interaction occurs in patients with Alzheimer's disease (AD). Eight-six AD patients, including 40 ApoE4 carriers and 46 non-carriers, underwent (18)F-FDG PET scanning at rest. ApoE groups were comparable for age, gender, age at onset and disease duration. SPM'99 was used to assess rCMRGlu correlations with age, differences between ApoE groups and ApoE by age interaction, correcting for disease severity. Results were reported at P0.001, uncorrected. Correlations between age and rCMRGlu confirmed the well-known negative relationship for both groups. Lower rCMRGlu was found within the frontal and cingulate areas for ApoE4 carriers as compared with the non-carriers. Additionally, a significant ApoE by age interaction was detected in the frontal and anterior cingulate cortex, with the ApoE4 carriers having a steeper regression slope with respect to the non-carriers. These results indicate that age-related regional rCMRglu decreases within the frontal and anterior cingulate areas may be more severe in AD patients carrying the ApoE4 allele.

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

Background : The recent introduction of acetylcholinesterase inhibitors (AChEIs) therapy for Alzheimer's Disease (AD) has led to the need to assess the brain's response to the therapy on an objective, neurophysiological basis. Brain perfusion single photon emission computed tomography (SPECT) was used in an open-label study to evaluate the effect of chronic Donepezil administration to a group of patients affected by mild to moderate AD, compared to a group of AD patients not receiving AChEIs and kept under observation for a similar period. Methods : Twenty-five consecutive patients with probable AD (National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria) (19 women, 6 men; mean age: 74.2±7.2; mean Mini-Mental State Examination score, MMSE: 19.8±3.5) underwent ( t 0 ) brain SPECT with 99m Tc-hexamethylpropylene-amine-oxime by a brain-dedicated, high-resolution camera and were re-evaluated ( t 1 ) after 11±2.6 months of chronic Donepezil administration (5 mg/day) (treated group). Thirteen AD patients (9 women, 4 men, mean age: 71.4±5.7, MMSE score: 20.6±3.5) were not treated with AChEIs and served as controls (untreated group). They were subjected to the same evaluation after 13±1.4 months as the treated group. Statistical parametric mapping (SPM) was employed to analyse SPECT findings. Results : The MMSE score declined significantly ( P t 0 to t 1 both in untreated (from 20.6±3.5 to 17.8±4.4) and in treated (from 19.8±3.5 to 17.8±4.1) group. At t 0 , the untreated group showed higher regional cerebral blood flow (rCBF) than the treated group in a frontal and a frontal-parietal region of the left hemisphere. Between t 0 and t 1 , significant rCBF reduction was observed in the temporal lobe and occipital-temporal cortex of the left hemisphere in the untreated group, whereas no significant change was observed in the treated group. The rCBF of the two groups did not significantly differ at t 1 . By covariate SPM analysis between t 0 and t 1 in treated patients, MMSE score changes correlated significantly with rCBF changes in a large left frontal-temporal region. Conclusions : Brain perfusion is preserved in AD patients undergoing chronic Donepezil therapy while it is reduced in untreated patients. SPECT is a promising tool with which to assess the impact of AChEI therapy on brain functioning of AD patients.

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

The aim of this study was to identify prostate-specific antigen (PSA) kinetics parameters predictive of [(18)F]fluorocholine positron emission tomography/computed tomography ((18)FC PET/CT) features worsening in a cohort of patients with biochemical failure after prostate cancer treatment.This longitudinal cohort study comprised 103 consecutive patients. All patients underwent two (18)FC PET/CT scans: one at baseline (PET1) and one after 6 months (PET2). Total PSA (tPSA), PSA velocity (vPSA), PSA doubling time (PSAdt), absolute variation in PSA values between PET2 and PET1 (ΔPSA), and percentage variation in PSA between the two PSA measurements (PSA%) were measured in each patient. Progression of disease on (18)FC PET/CT findings was compared with the PSA kinetics parameters. The major outcome measure was disease progression at PET2.(18)FC PET/CT progression between PET1 and PET2 was reported in 64 patients (62.1%), while in 39 cases it remained unvaried. The following PSA kinetic parameters correlated with worsened (18)FC PET/CT findings: ΔPSA5 ng/ml [odds ratio (OR = 6.44, 95% confidence interval (CI) 1.04-39.6; p = 0.04], vPSA6 ng/ml/month (OR = 5.2, 95% CI 0.9-29.8; p = 0.05) and PSAdt6 months (OR = 5.2, 95% CI 0.4-5.4; p = 0.03). From receiver operating characteristics (ROC) analysis, the combination with the three PSA kinetics parameters for predicting worsened (18)FC PET/CT findings resulted in a sensitivity of 86% (95% CI 77-92%) and specificity of 77% (95% CI 65-85%).PSA kinetics is strictly related to (18)FC PET/CT findings. In patients with biochemical relapse, ΔPSA5 ng/ml, PSAdt6 months and vPSA6 ng/ml/month are highly predictive of (18)FC PET/CT features worsening, independently from the treatment received.

Orbitofrontal metabolic impairment is characteristic of the frontal variant of frontotemporal dementia (fv-FTD), as are early changes in emotional and social conduct. Two main types of behavioral disturbances have been distinguished in fv-FTD patients: apathetic and disinhibited manifestations. In this study, we searched for relationships between brain metabolism and presence of apathetic or disinhibited behavior. Metabolic activity and behavioral data were collected in 41 fv-FTD patients from European PET centers. A conjunction analysis of the PET data showed an expected impairment of metabolic activity in the anterior cingulate, ventromedial and orbital prefrontal cortex, the dorsolateral prefrontal cortex and the left anterior insula in fv-FTD subjects compared to matched controls. A correlation was observed between disinhibition scores on the Neuropsychiatric Inventory scale and a cluster of voxels located in the posterior orbitofrontal cortex (6, 28, –24). Comparison of brain activity between apathetic and nonapathetic fv-FTD patients from two centers also revealed a specific involvement of the posterior orbitofrontal cortex in apathetic subjects (4, 22, –22). The results confirm that the main cerebral metabolic impairment in fv-FTD patients affects areas specializing in emotional evaluation and demonstrate that decreased orbitofrontal activity is related to both disinhibited and apathetic syndromes in fv-FTD. Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Background Subjects with amnesic mild cognitive impairment (aMCI) may include patients at high risk for progression to Alzheimer disease (AD) and a population with different underlying pathologic conditions. Objective To evaluate the potential roles of positron emission tomography with fluodeoxyglucose F 18 ( 18 FDG-PET) and memory scores in identifying subjects with aMCI and in predicting progression to dementia. Design, Setting, and Patients Sixty-seven patients at European centers for neurologic and AD care who were diagnosed as having aMCI each underwent an extensive clinical and neuropsychological examination and an 18 FDG-PET study. Forty-eight subjects were followed up periodically for at least 1 year, and progression to dementia was evaluated. Main Outcome Measures Brain glucose metabolism and memory scores. Results Fourteen subjects with aMCI who converted to AD within 1 year showed bilateral hypometabolism in the inferior parietal, posterior cingulate, and medial temporal cortex. Subjects with “stable” aMCI presented with hypometabolism in the dorsolateral frontal cortex. The severity of memory impairment, as evaluated by the California Verbal Learning Test–Long Delay Free Recall scores, correlated with the following brain metabolic patterns: scores less than 7 were associated with a typical 18 FDG-PET AD pattern, and scores of 7 or higher were associated with hypometabolism in the dorsolateral frontal cortex and no progression to AD. Conclusion These data provide evidence for clinical and functional heterogeneity among subjects with aMCI and suggest that 18 FDG-PET findings combined with memory scores may be useful in predicting short-term conversion to AD.

In acute myocardial infarction (AMI) treated by primary percutaneous coronary intervention (PCI), there is a direct relationship between myocardial damage and consequent left ventricular (LV) functional impairment. It is however unclear whether there is a safety threshold below which infarct size does not significantly affect LV ejection fraction (EF). The aim of this study was to evaluate the relationship between infarct size and LVEF in AMI patients treated by successful PCI using a specific statistical approach to identify a possible safety threshold.Among patients with recent AMI submitted to perfusion gated single photon emission computed tomography (SPECT) to define the infarct size, the data of 427 subjects with sizable infarct size were considered. The relationship between infarct size and LVEF was analysed using a simple segmented regression (SSR) model and an iterative algorithm based on robust least squares (RLS) for parameter estimation.The RLS algorithm detected two break points in the SSR model, set at infarct size values of 11.0 and 51.5 %. Because the slope coefficients of the two extreme segments of the regression line were not significant, by constraining such segments to zero slope in the SSR model, the lower break point was identified at infarct size = 8 % and the upper one at 45 %.Using a rigorous statistical approach, it is possible to demonstrate that below a threshold of 8 % the infarct size apparently does not affect the LVEF and therefore a safety threshold could be set at this value. Furthermore, the same analysis suggests that the relationship between infarct size and LVEF impairment is lost for an infarct size45 %.

In the recently revised diagnostic criteria for Alzheimer disease (AD), the National Institute on Aging and Alzheimer Association suggested that confidence in diagnosing dementia due to AD and mild cognitive impairment (MCI) due to AD could be improved by the use of certain biomarkers, such as (18)F-FDG PET evidence of hypometabolism in AD-affected brain regions. Three groups have developed automated data analysis techniques to characterize the AD-related pattern of hypometabolism in a single measurement. In this study, we sought to directly compare the ability of these three (18)F-FDG PET data analysis techniques--the PMOD Alzheimer discrimination analysis tool, the hypometabolic convergence index, and a set of meta-analytically derived regions of interest reflecting AD hypometabolism pattern (metaROI)--to distinguish moderate or mild AD dementia patients and MCI patients who subsequently converted to AD dementia from cognitively normal older adults.One hundred sixty-six (18)F-FDG PET patients from the AD Neuroimaging Initiative, 308 from the Network for Efficiency and Standardization of Dementia Diagnosis, and 176 from the European Alzheimer Disease Consortium PET study were categorized, with masking of group classification, as AD, MCI, or healthy control. For each AD-related (18)F-FDG PET index, receiver-operating-characteristic curves were used to characterize and compare subject group classifications.The 3 techniques were roughly comparable in their ability to distinguish each of the clinical groups from cognitively normal older adults with high sensitivity and specificity. Accuracy of classification (in terms of area under the curve) in each clinical group varied more as a function of dataset than by technique. All techniques were differentially sensitive to disease severity, with the classification accuracy for MCI due to AD to moderate AD varying from 0.800 to 0.949 (PMOD Alzheimer tool), from 0.774 to 0.967 (metaROI), and from 0.801 to 0.983 (hypometabolic convergence index).The 3 tested techniques have the potential to help detect AD in research and clinical settings. Additional efforts are needed to clarify their ability to address particular scientific and clinical questions. Their incremental diagnostic value over other imaging and biologic markers makes them easier to implement by other groups for these purposes.