Molecularly imprinted electrochemical sensor for the ultrasensitive detection of cytochrome c.

Cytochrome c (Cyt c) is an important biomarker for the early stage of apoptosis that plays a role in the diagnosis and therapy of several diseases including cancer. Here, an electrochemical sensor based on molecularly imprinted polymer (MIP) for the ultrasensitive detection of Cyt c is studied. It is prepared by electropolymerization of o-phenylenediamine in the presence of Cyt c as template, followed by solvent extraction, resulting in the formation of Cyt c recognition sites. The MIP is characterised by cyclic voltammetry and differential pulse voltammetry, using ferrocenecarboxylic acid as redox probe. Voltammetric data indicates that the MIP-sensor behaves as an electrode with partially blocked surface. The partition isotherm obtained fits the Langmuir model, indicating a high affinity for Cyt c, with an association constant Ka = 5 × 10 11 M-1. DPV measurements allow to achieve extremely high analytical sensitivity and low detection limit, in the femtomolar range, with negligible unspecific adsorption. Satisfactory analytical recovery tests performed in the presence of possible interfering proteins and in diluted human serum confirmed the selectivity of the MIP-sensor as well as its potential applicability for real samples analysis.

Advanced Electrochemical and Opto-Electrochemical Biosensors for Quantitative Analysis of Disease Markers and Viruses.

Instrumental laboratory methods for biochemical and chemical analyses have reached a high level of reliability with excellent sensitivity and specificity [...].

Brain 18 F-Florbetapir PET/CT Findings in an Early-onset Alzheimer Disease Patient Carrying Presenilin-1 G378E Mutation.

Positron emission tomography (PET) with 18 F-Fluorodeoxyglucose ( 18 F-FDG) plays an outstanding role in the diagnostic work-up of dementia. Amyloid PET imaging is a complementary imaging technique for the early detection of Alzheimer disease (AD). ß-amyloid precursor protein ( APP ), Presenilin-1 ( PSEN1 ) and Presenilin-2 ( PSEN2 ) are the 3 main causative genes responsible for autosomal dominant early-onset Alzheimer disease (EOAD). This is the first report of 18 F-Florbetapir amyloid imaging findings in a 35-year-old male patient with EOAD carrying the G378E mutation in PSEN1 gene. Brain computed tomography (CT) and magnetic resonance imaging scans showed remarkable cerebral atrophy with dilatation of the cerebrospinal fluid spaces; furthermore, a 18 F-Florbetapir PET/CT scan demonstrated also widespread remarkable accumulation of the amyloid tracer in the cerebral cortex, with reduction of the normal contrast between white and gray matter and flattening of the external cortical margins. Furthermore, PET/CT showed intense 18 F-florbetapir uptake in the striatum and in the thalamus bilaterally. Our case supports the usefulness of amyloid PET imaging in the diagnostic work-up of EOAD.

Added value of semiquantitative analysis of brain FDG-PET for the differentiation between MCI-Lewy bodies and MCI due to Alzheimer's disease.

PURPOSE: FDG-PET is an established supportive biomarker in dementia with Lewy bodies (DLB), but its diagnostic accuracy is unknown at the mild cognitive impairment (MCI-LB) stage when the typical metabolic pattern may be difficultly recognized at the individual level. Semiquantitative analysis of scans could enhance accuracy especially in less skilled readers, but its added role with respect to visual assessment in MCI-LB is still unknown. METHODS: We assessed the diagnostic accuracy of visual assessment of FDG-PET by six expert readers, blind to diagnosis, in discriminating two matched groups of patients (40 with prodromal AD (MCI-AD) and 39 with MCI-LB), both confirmed by in vivo biomarkers. Readers were provided in a stepwise fashion with (i) maps obtained by the univariate single-subject voxel-based analysis (VBA) with respect to a control group of 40 age- and sex-matched healthy subjects, and (ii) individual odds ratio (OR) plots obtained by the volumetric regions of interest (VROI) semiquantitative analysis of the two main hypometabolic clusters deriving from the comparison of MCI-AD and MCI-LB groups in the two directions, respectively. RESULTS: Mean diagnostic accuracy of visual assessment was 76.8 ± 5.0% and did not significantly benefit from adding the univariate VBA map reading (77.4 ± 8.3%) whereas VROI-derived OR plot reading significantly increased both accuracy (89.7 ± 2.3%) and inter-rater reliability (ICC 0.97 [0.96-0.98]), regardless of the readers' expertise. CONCLUSION: Conventional visual reading of FDG-PET is moderately accurate in distinguishing between MCI-LB and MCI-AD, and is not significantly improved by univariate single-subject VBA but by a VROI analysis built on macro-regions, allowing for high accuracy independent of reader skills.

Evaluation of Age and Sex-Related Metabolic Changes in Healthy Subjects: An Italian Brain 18F-FDG PET Study.

BACKGROUND: 18F-fluorodeoxyglucose (18F-FDG) positron-emission-tomography (PET) allows detection of cerebral metabolic alterations in neurological diseases vs. normal aging. We assess age- and sex-related brain metabolic changes in healthy subjects, exploring impact of activity normalization methods. METHODS: brain scans of Italian Association of Nuclear Medicine normative database (151 subjects, 67 Males, 84 Females, aged 20-84) were selected. Global mean, white matter, and pons activity were explored as normalization reference. We performed voxel-based and ROI analyses using SPM12 and IBM-SPSS software. RESULTS: SPM proved a negative correlation between age and brain glucose metabolism involving frontal lobes, anterior-cingulate and insular cortices bilaterally. Narrower clusters were detected in lateral parietal lobes, precuneus, temporal pole and medial areas bilaterally. Normalizing on pons activity, we found a more significant negative correlation and no positive one. ROIs analysis confirmed SPM results. Moreover, a significant age × sex interaction effect was revealed, with worse metabolic reduction in posterior-cingulate cortices in females than males, especially in post-menopausal age. CONCLUSIONS: this study demonstrated an age-related metabolic reduction in frontal lobes and in some parieto-temporal areas more evident in females. Results suggested pons as the most appropriate normalization reference. Knowledge of age- and sex-related cerebral metabolic changes is critical to correctly interpreting brain 18F-FDG PET imaging.

SARS-CoV-2-related encephalitis with prominent parkinsonism: clinical and FDG-PET correlates in two patients.

Considering the similarities with other pandemics due to respiratory virus infections and subsequent development of neurological disorders (e.g. encephalitis lethargica after the 1918 influenza), there is growing concern about a possible new wave of neurological complications following the worldwide spread of SARS-CoV-2. However, data on COVID-19-related encephalitis and movement disorders are still limited. Herein, we describe the clinical and neuroimaging (FDG-PET/CT, MRI and DaT-SPECT) findings of two patients with COVID-19-related encephalopathy who developed prominent parkinsonism. None of the patients had previous history of parkinsonian signs/symptoms, and none had prodromal features of Parkinson's disease (hyposmia or RBD). Both developed a rapidly progressive form of atypical parkinsonism along with distinctive features suggestive of encephalitis. A possible immune-mediated etiology was suggested in Patient 2 by the presence of CSF-restricted oligoclonal bands, but none of the patients responded favorably to immunotherapy. Interestingly, FDG-PET/CT findings were similar in both cases and reminiscent of those observed in post-encephalitic parkinsonism, with cortical hypo-metabolism associated with hyper-metabolism in the brainstem, mesial temporal lobes, and basal ganglia. Patient's FDG-PET/CT findings were validated by performing a Statistical Parametric Mapping analysis and comparing the results with a cohort of healthy controls (n = 48). Cerebrum cortical thickness map was obtained in Patient 1 from MRI examinations to evaluate the structural correlates of the metabolic alterations detected with FDG-PET/CT. Hypermetabolic areas correlated with brain regions showing increased cortical thickness, suggesting their involvement during the inflammatory process. Overall, these observations suggest that SARS-CoV-2 infection may trigger an encephalitis with prominent parkinsonism and distinctive brain metabolic alterations.

Surface Enhanced Raman Spectroscopy With Electrodeposited Copper Ultramicro-Wires With/Without Silver Nanostars Decoration.

The electrochemical preparation of arrays of copper ultramicrowires (CuUWs) by using porous membranes as templates is critically revisited, with the goal of obtaining cheap but efficient substrates for surface enhanced Raman spectroscopy (SERS). The role of the materials used for the electrodeposition is examined, comparing membranes of anodized aluminum oxide (AAO) vs. track-etched polycarbonate (PC) as well as copper vs. glassy carbon (GC) as electrode material. A voltammetric study performed on bare electrodes and potentiostatic tests on membrane coated electrodes allowed the optimization of the deposition parameters. The final arrays of CuUWs were obtained by chemical etching of the template, with NaOH for AAO and CH2Cl2 for PC. After total etching of the template, SERS spectra were recorded on CuUWs using benzenethiol as SERS probe with known spectral features. The CuUW substrates displayed good SERS properties, providing enhancement factor in the 103-104 range. Finally, it was demonstrated that higher Raman enhancement can be achieved when CuUWs are decorated with silver nanostars, supporting the formation of SERS active hot-spots at the bimetallic interface.

Electrochemical preconcentration coupled with spectroscopic techniques for trace lead analysis in olive oils.

In this paper we present a novel combined electrochemical-spectroscopic approach suitable to monitor trace levels of heavy metals directly in edible oils. The method is based on the electrochemical preconcentration/extraction of the analyte from the tested real matrix by cathodic deposition onto a Pt working electrode, then transfer and anodic re-oxidation of the metallic deposit to a "clean" aqueous solution, suitable for the subsequent spectroscopic analysis. The procedure has been here focused to the determination of lead in extra virgin olive oil (EVOO), performed by applying ICP-QMS or GFAAS techniques. To this aim, the EVOO samples were mixed with proper amounts of the room temperature ionic liquid (RTIL) [P14,6,6,6]+[NTf2]-, in order to obtain a non-aqueous supporting electrolyte suitable for the electrodeposition process. The feasibility and performance of the analytical strategy were at first tested in standard solutions of Pb(II) in RTIL, produced by anodic dissolution of lead in the RTIL, as well as in olive oil samples mixed with 0.5 M RTIL and spiked with known amounts of Pb(II). The optimisation of the electrochemical parameters was achieved by applying a D-Optimal Design, properly set up to optimise the efficiency of the deposition and re-oxidation steps, quantitative recovery and measurement time. Finally, the analytical procedure was applied to the determination of Pb content in some Italian EVOOs, without any need of performing mineralization pretreatments. Data obtained with the proposed procedure satisfactorily agree with those achieved by ICP-QMS analysis after microwave digestion, being differences between the two approaches within 10%, with the advantage of reducing to half the pretreatment time, operating at room temperature and avoiding the use of aggressive solvents.

Extrastriatal dopaminergic and serotonergic pathways in Parkinson's disease and in dementia with Lewy bodies: a 123I-FP-CIT SPECT study.

PURPOSE: The aim of the study was to evaluate extrastriatal dopaminergic and serotonergic pathways in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB) using 123I-FP-CIT SPECT imaging. METHODS: The study groups comprised 56 PD patients without dementia, 41 DLB patients and 54 controls. Each patient underwent a standardized neurological examination and 123I-FP-CIT SPECT. Binding in nigrostriatal and extrastriatal regions of interest was calculated in each patient from spatially normalized images. The occipital-adjusted specific to nondisplaceable binding ratio (SBR) in the different regions was compared among the PD patients, DLB patients and controls adjusting for the effects of age, sex, disease duration and serotonergic/dopaminergic treatment. Covariance analysis was used to determine the correlates of local and long-distance regions with extrastriatal 123I-FP-CIT deficits. RESULTS: Both PD and DLB patients showed lower 123I-FP-CIT SPECT SBR in several regions beyond the nigrostriatal system, especially the insula, cingulate and thalamus. DLB patients showed significantly lower 123I-FP-CIT SBR in the thalamus than controls and PD patients. Thalamic and cingulate 123I-FP-CIT SBR deficits were correlated, respectively, with limbic serotonergic and widespread cortical monoaminergic projections only in DLB patients but exhibited only local correlations in PD patients and controls. CONCLUSION: PD and DLB patients both showed insular dopamine deficits, whereas impairment of thalamic serotonergic pathways was specifically associated with DLB. Longitudinal studies are necessary to determine the clinical value of the assessment of extrastriatal 123I-FP-CIT SPECT.

Electrochemical Immunosensor Based on Nanoelectrode Ensembles for the Serological Analysis of IgG-type Tissue Transglutaminase.

Celiac disease (CD) is a gluten-dependent autoimmune disorder affecting a significant percentage of the general population, with increasing incidence particularly for children. Reliable analytical methods suitable for the serological diagnosis of the disorder are urgently required for performing both the early diagnosis and the follow-up of a patient adhering to a gluten-free diet. Herein we report on the preparation and application of a novel electrochemical immunosensor based on the use of ensembles of gold nanoelectrodes (NEEs) for the detection of anti-tissue transglutaminase (anti-tTG), which is considered one reliable serological marker for CD. To this end, we take advantage of the composite nature of the nanostructured surface of membrane-templated NEEs by functionalizing the polycarbonate surface of the track-etched membrane with tissue transglutaminase. Incubation of the functionalized NEE in anti-tTG samples results in the capture of the anti-tTG antibody. Confirmation of the recognition event is achieved by incubating the NEE with a secondary antibody labelled with horseradish peroxidase (HRP): in the presence of H2O2 as substrate and hydroquinone as redox mediator, an electrocatalytic current is indeed generated whose increment is proportional to the amount of anti-tTG captured from the sample. The optimized sensor allows a detection limit of 1.8 ng mL-1, with satisfactory selectivity and reproducibility. Analysis of serum samples from 28 individuals, some healthy and some affected by CD, furnished analytical results comparable with those achieved by classical fluoroenzyme immunoassay (FEIA). We note that the NEE-based immunosensor developed here detects the IgG isotype of anti-tTG, while FEIA detects the IgA isotype, which is not a suitable diagnostic marker for IgA-deficient patients.

Plasma Activation of Copper Nanowires Arrays for Electrocatalytic Sensing of Nitrate in Food and Water.

Electrochemical methods for nitrate detection are very attractive since they are suitable for in-field and decentralized monitoring. Copper electrodes are often used to this aim as this metal presents interesting electrocatalytic properties towards nitrate reduction. In this research, we study improvements in the electrochemical analysis of nitrate in natural water and food by taking advantage of the detection capabilities of ensembles of copper nanowire electrodes (CuWNEEs). These electrodes are prepared via template electrodeposition of copper within the nanopores of track-etched polycarbonate (PC) membranes. A critical step in the preparation of these sensors is the removal of the template. Here, we applied the combination of chemical etching with atmospheric plasma cleaning which proved suitable for improving the performance of the nanostructured copper electrode. Analytical results obtained with the CuWNEE sensor for nitrate analyses in river water samples compare satisfactorily with those achieved by standard chromatographic or spectroscopic methods. Experimental results concerning the application of the CuWNEEs for nitrate analysis in food samples are also presented and discussed, with focus on nitrate detection in leafy vegetables.

Electrochemosensor for Trace Analysis of Perfluorooctanesulfonate in Water Based on a Molecularly Imprinted Poly( o-phenylenediamine) Polymer.

This work is aimed at developing an electrochemical sensor for the sensitive and selective detection of trace levels of perfluorooctanesulfonate (PFOS) in water. Contamination of waters by perfluorinated alkyl substances (PFAS) is a problem of global concern due to their suspected toxicity and ability to bioaccumulate. PFOS is the perfluorinated compound of major concern, as it has the lowest suggested control concentrations. The sensor reported here is based on a gold electrode modified with a thin coating of a molecularly imprinted polymer (MIP), prepared by anodic electropolymerization of o-phenylenediamine (o-PD) in the presence of PFOS as the template. Activation of the sensor is achieved by template removal with suitable a solvent mixture. Voltammetry, a quartz crystal microbalance, scanning electron microscopy and elemental analysis were used to monitor the electropolymerization process, template removal, and binding of the analyte. Ferrocenecarboxylic acid (FcCOOH) has been exploited as an electrochemical probe able to generate analytically useful voltammetric signals by competing for the binding sites with PFOS, as the latter is not electroactive. The sensor has a low detection limit (0.04 nM), a satisfactory selectivity, and is reproducible and repeatable, giving analytical results in good agreement with those obtained by HPLC-MS/MS analyses.

Quantitative appraisal of the Amyloid Imaging Taskforce appropriate use criteria for amyloid-PET.

INTRODUCTION: We test the hypothesis that amyloid-positron emission tomography prescriptions, considered appropriate based on the Amyloid Imaging Taskforce (AIT) criteria, lead to greater clinical utility than AIT-inappropriate prescriptions. METHODS: We compared the clinical utility between patients who underwent amyloid-positron emission tomography appropriately or inappropriately and among the subgroups of patients defined by the AIT criteria. Finally, we performed logistic regressions to identify variables associated with clinical utility. RESULTS: We identified 171 AIT-appropriate and 67 AIT-inappropriate patients. AIT-appropriate and AIT-inappropriate cases did not differ in any outcomes of clinical utility (P > .05). Subgroup analysis denoted both expected and unexpected results. The logistic regressions outlined the primary role of clinical picture and clinical or neuropsychological profile in identifying patients benefitting from amyloid-positron emission tomography. DISCUSSION: Contrary to our hypothesis, also AIT-inappropriate prescriptions were associated with clinical utility. Clinical or neuropsychological variables, not taken into account by the AIT criteria, may help further refine criteria for appropriateness.

Association of postoperative delirium with markers of neurodegeneration and brain amyloidosis: a pilot study.

The aim of the study was to investigate the association between postoperative delirium (POD) and in vivo markers of Alzheimer's disease pathology in nondemented hip fracture surgery patients. POD was assessed with the Confusion Assessment Method. Amyloid load was quantified on 18F-Flutemetamol positron emission tomography images as standardized uptake value ratio. Secondary outcome measures were gray matter volumes, white matter integrity, and functional connectivity at rest. All the patients with POD (POD+, N = 5) were amyloid negative (standardized uptake value ratio <0.59), whereas 6 out of 11 patients without POD (POD-) showed brain amyloid positivity. POD+ compared to POD- displayed: lower gray matter volumes in the amygdala (p = 0.003), in the middle temporal gyrus and in the anterior cingulate cortex (p < 0.001), increased diffusivity in the genu of the corpus callosum and in the anterior corona radiata (p < 0.05), and higher functional connectivity within the default mode network (p < 0.001). POD patients showed altered gray and white matter integrity in the fronto-limbic regions in absence of brain amyloidosis. Based on this preliminary investigation, delirium pathophysiology might be independent of Alzheimer's disease. Future studies on larger samples are needed to confirm this hypothesis.

Cerebral PET glucose hypometabolism in subjects with mild cognitive impairment and higher EEG high-alpha/low-alpha frequency power ratio.

In Alzheimer's disease (AD) research, both 2-deoxy-2-(18F)fluoro-D-glucose (FDG) positron emission tomography (PET) and electroencephalography (EEG) are reliable investigational modalities. The aim of this study was to investigate the associations between EEG High-alpha/Low-alpha (H-alpha/L-alpha) power ratio and cortical glucose metabolism. A total of 23 subjects with mild cognitive impairment (MCI) underwent FDG-PET and EEG examinations. H-alpha/L-alpha power ratio was computed for each subject and 2 groups were obtained based on the increase of the power ratio. The subjects with higher H-alpha/L-alpha power ratio showed a decrease in glucose metabolism in the hub brain areas previously identified as typically affected by AD pathology. In subjects with higher H-alpha/L-alpha ratio and lower metabolism, a "double alpha peak" was identified in the EEG spectrum and a U-shaped correlation between glucose metabolism and increase of H-alpha/L-alpha power ratio has been found. Moreover, in this group, a conversion rate of 62.5% at 24 months was detected, significantly different from the chance percentage expected. The neurophysiological meaning of the interplay between alpha oscillations and glucose metabolism and the possible interest of the H-alpha/L-alpha power ratio as a clinical biomarker in AD have been discussed.

Electrochemical preparation of standard solutions of Pb(II) ions in ionic liquid for analysis of hydrophobic samples: The olive oil case.

In this paper we present an electrochemical approach to prepare standard solutions of metal ions in a room temperature ionic liquid (IL), which can find useful application for analysis in hydrophobic matrices. The method, developed here for the case of lead ions, is based on the galvanostatic dissolution of a lead anode dipped directly in a suitable IL, namely tri-hexyl(tetradecyl)phosphonium bis (trifluoromethylsulfonyl) imide ([P14,6,6,6]+[NTf2]-). After each oxidation step, the metal dissolution process in the IL solutions was monitored by cyclic voltammetric measurements at a glassy carbon disk electrode. The results indicated that the peak current relevant to the reduction of the electro-generated Pb(II) increased linearly while increasing the oxidation time. By varying the oxidation time from 200 to 6000s, a set of Pb(II)/[P14,6,6,6]+[NTf2]- solutions at concentrations ranging between 10 and 300µgg-1 was prepared. To validate the efficiency of the electrochemical procedure to produce metal ion standard solutions, the Pb content was quantified by developing a microwave digestion procedure specifically suitable for the IL medium, followed by ICP-QMS analysis in the digested standards. The results indicated a satisfactory agreement between concentrations found by ICP-QMS and calculated from electrochemical data, with a coulometric efficiency of Pb(II) generation in ionic liquid ≥95.6%. Finally, the applicability of the Pb(II)/IL solutions as standards for analyses in hydrophobic media was tested by determining, by ICP-QMS, the Pb content in an extra-virgin olive oil spiked with known amounts of a Pb(II)/IL standard. Satisfactory Pb recoveries, ≥96%, were measured.

Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly.

The pathway leading from amyloid-ß deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer's disease (AD). However, what drives amyloid buildup in sporadic nongenetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (1) GMB taxa with pro- and anti-inflammatory activity; and (2) peripheral inflammation in cognitively impaired patients. We measured the stool abundance of selected bacterial GMB taxa (Escherichia/Shigella, Pseudomonas aeruginosa, Eubacterium rectale, Eubacterium hallii, Faecalibacterium prausnitzii, and Bacteroides fragilis) and the blood expression levels of cytokines (pro-inflammatory cytokines: CXCL2, CXCL10, interleukin [IL]-1ß, IL-6, IL-18, IL-8, inflammasome complex (NLRP3), tumor necrosis factor-alpha [TNF-α]; anti-inflammatory cytokines: IL-4, IL-10, IL-13) in cognitively impaired patients with (n = 40, Amy+) and with no brain amyloidosis (n = 33, Amy-) and also in a group of controls (n = 10, no brain amyloidosis and no cognitive impairment). Amy+ patients showed higher levels of pro-inflammatory cytokines (IL-6, CXCL2, NLRP3, and IL-1ß) compared with both controls and with Amy- patients. A reduction of the anti-inflammatory cytokine IL-10 was observed in Amy+ versus Amy-. Amy+ showed lower abundance of E. rectale and higher abundance of Escherichia/Shigella compared with both healthy controls (fold change, FC = -9.6, p < 0.001 and FC = +12.8, p < 0.001, respectively) and to Amy- (FC = -7.7, p < 0.001 and FC = +7.4, p = 0.003). A positive correlation was observed between pro-inflammatory cytokines IL-1ß, NLRP3, and CXCL2 with abundance of the inflammatory bacteria taxon Escherichia/Shigella (rho = 0.60, p < 0.001; rho = 0.57, p < 0.001; and rho = 0.30, p = 0.007, respectively) and a negative correlation with the anti-inflammatory E. rectale (rho = -0.48, p < 0.001; rho = -0.25, p = 0.024; rho = -0.49, p < 0.001). Our data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella, and a reduction in the abundance of an anti-inflammatory taxon, E. rectale, are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. A possible causal relation between GMB-related inflammation and amyloidosis deserves further investigation.

Assessment of the Incremental Diagnostic Value of Florbetapir F 18 Imaging in Patients With Cognitive Impairment: The Incremental Diagnostic Value of Amyloid PET With [18F]-Florbetapir (INDIA-FBP) Study.

IMPORTANCE: Cerebral amyloidosis is a key abnormality in Alzheimer disease (AD) and can be detected in vivo with positron emission tomography (PET) ligands. Although amyloid PET has clearly demonstrated analytical validity, its clinical utility is debated. OBJECTIVE: To evaluate the incremental diagnostic value of amyloid PET with florbetapir F 18 in addition to the routine clinical diagnostic assessment of patients evaluated for cognitive impairment. DESIGN, SETTING, AND PARTICIPANTS: The Incremental Diagnostic Value of Amyloid PET With [18F]-Florbetapir (INDIA-FBP) Study is a multicenter study involving 18 AD evaluation units from eastern Lombardy, Northern Italy, 228 consecutive adults with cognitive impairment were evaluated for AD and other causes of cognitive decline, with a prescan diagnostic confidence of AD between 15% and 85%. Participants underwent routine clinical and instrumental diagnostic assessment. A prescan diagnosis was made, diagnostic confidence was estimated, and drug treatment was provided. At the time of this workup, an amyloid PET/computed tomographic scan was performed, and the result was communicated to physicians after workup completion. Physicians were asked to review the diagnosis, diagnostic confidence, and treatment after the scan. The study was conducted from August 5, 2013, to December 31, 2014. MAIN OUTCOMES AND MEASURES: Primary outcomes were prescan to postscan changes of diagnosis, diagnostic confidence, and treatment. RESULTS: Of the 228 participants, 107 (46%) were male; mean (SD) age was 70.5 (7) years. Diagnostic change occurred in 46 patients (79%) having both a previous diagnosis of AD and an amyloid-negative scan (P < .001) and in 16 (53%) of those with non-AD diagnoses and an amyloid-positive scan (P < .001). Diagnostic confidence in AD diagnosis increased by 15.2% in amyloid-positive (P < .001; effect size Cohen d = 1.04) and decreased by 29.9% in amyloid-negative (P < .001; d = -1.19) scans. Acetylcholinesterase inhibitors and memantine hydrochloride were introduced in 61 (65.6%) patients with positive scan results who had not previously received those drugs, and the use of the drugs was discontinued in 6 (33.3%) patients with negative scan results who were receiving those drugs (P < .001). CONCLUSIONS AND RELEVANCE: Amyloid PET in addition to routine assessment in patients with cognitive impairment has a significant effect on diagnosis, diagnostic confidence, and drug treatment. The effect on health outcomes, such as morbidity and mortality, remains to be assessed.

Standardized Uptake Value Ratio-Independent Evaluation of Brain Amyloidosis.

The assessment of in vivo18F images targeting amyloid deposition is currently carried on by visual rating with an optional quantification based on standardized uptake value ratio (SUVr) measurements. We target the difficulties of image reading and possible shortcomings of the SUVr methods by validating a new semi-quantitative approach named ELBA. ELBA involves a minimal image preprocessing and does not rely on small, specific regions of interest (ROIs). It evaluates the whole brain and delivers a geometrical/intensity score to be used for ranking and dichotomic assessment. The method was applied to adniimages 18F-florbetapir images from the ADNI database. Five expert readers provided visual assessment in blind and open sessions. The longitudinal trend and the comparison to SUVr measurements were also evaluated. ELBA performed with area under the roc curve (AUC) = 0.997 versus the visual assessment. The score was significantly correlated to the SUVr values (r = 0.86, p < 10-4). The longitudinal analysis estimated a test/retest error of ≃2.3%. Cohort and longitudinal analysis suggests that the ELBA method accurately ranks the brain amyloid burden. The expert readers confirmed its relevance in aiding the visual assessment in a significant number (85) of difficult cases. Despite the good performance, poor and uneven image quality constitutes the major limitation.

(123) I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography and (123) I-metaiodobenzylguanidine myocardial scintigraphy in differentiating dementia with lewy bodies from other dementias: A comparative study.

OBJECTIVE: To compare the diagnostic value of striatal (123) I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123) I-FP-CIT) single photon emission computed tomography (SPECT) and (123) I-metaiodobenzylguanidine ((123) I-MIBG) myocardial scintigraphy in differentiating dementia with Lewy bodies (DLB) from other dementia types. METHODS: This prospective longitudinal study included 30 patients with a clinical diagnosis of DLB and 29 patients with non-DLB dementia (Alzheimer disease, n = 16; behavioral variant frontotemporal dementia, n = 13). All patients underwent (123) I-FP-CIT SPECT and (123) I-MIBG myocardial scintigraphy within a few weeks of clinical diagnosis. All diagnoses at each center were agreed upon by the local clinician and an independent expert, both unaware of imaging data, and re-evaluated after 12 months. Each image was visually classified as either normal or abnormal by 3 independent nuclear physicians blinded to patients' clinical data. RESULTS: Overall, sensitivity and specificity to DLB were respectively 93% and 100% for (123) I-MIBG myocardial scintigraphy, and 90% and 76% for (123) I-FP-CIT SPECT. Lower specificity of striatal compared to myocardial imaging was due to decreased (123) I-FP-CIT uptake in 7 non-DLB subjects (3 with concomitant parkinsonism) who had normal (123) I-MIBG myocardial uptake. Notably, in our non-DLB group, myocardial imaging gave no false-positive readings even in those subjects (n = 7) with concurrent medical illnesses (diabetes and/or heart disease) supposed to potentially interfere with (123) I-MIBG uptake. INTERPRETATION: (123) I-FP-CIT SPECT and (123) I-MIBG myocardial scintigraphy have similar sensitivity for detecting DLB, but the latter appears to be more specific for excluding non-DLB dementias, especially when parkinsonism is the only "core feature" exhibited by the patient. Our data also indicate that the potential confounding effects of diabetes and heart disease on (123) I-MIBG myocardial scintigraphy results might have been overestimated. Ann Neurol 2016;80:368-378.