Diabetes Mellitus (DM) has been recognized as a potential risk factor and disease-modifier in Parkinson’s Disease (PD), being associated with worse motor and cognitive outcomes, and altered susceptibility of neural pathways. This study investigated the impact of DM on nigrostriatal dopaminergic vulnerability independently of disease severity in drug-naïve PD patients. This study analyzed two independent cohorts of PD patients (multi-center PPMI n = 174, single-center UniBS n = 95). Patients with and without DM were first compared and then matched for age, sex, and clinical severity. All patients underwent baseline 123I-FP-CIT imaging to quantify dopamine transporter binding. Dopaminergic binding, neural reserve index and molecular connectivity patterns were compared between severity-matched groups. Patients with DM were older, predominantly male, and exhibited worse non-motor and cognitive symptoms. After severity matching, PD-DM exhibited more preserved nigrostriatal dopamine uptake compared to PD-n. PD-DM also showed fewer nigrostriatal dopaminergic connectivity alterations (10

Both post-mortem and in vivo data argue for dopamine dysfunction in patients with Alzheimer’s Disease (AD). However, the timing and regional progression of dopaminergic systems alterations in AD are still debated. The aim of the study was to investigate in vivo the pattern of dopaminergic changes and connectivity using DAT-SPECT imaging in patients across the AD spectrum. Fifty-nine AD patients (n = 21 AD-MCI; n = 38 AD-DEM) and a control group (CG) of n = 45 age- and sex-matched individuals entered the study and underwent 123I-FP-CIT dopaminergic imaging. The occipital binding was used as reference region to obtain single-subject binding in different brain regions. Between-group differences in 123I-FP-CIT binding in both mesolimbic and nigrostriatal dopaminergic pathways were assessed using an ANCOVA test, adjusting for the effect of center of imaging acquisition, age, and sex. Regions resulting from the voxel-wise direct comparison between AD-MCI and AD-DEM were considered as a seed of interest for a voxel-wise interregional correlation analysis. Both AD-MCI and AD-DEM patients showed dopaminergic depletion within the basal ganglia, whereas cortico-limbic regions (namely hippocampus, amygdala, anterior and middle cingulate, frontal cortex and thalamus) resulted impaired only in the dementia phase. The brain voxel-wise interregional correlation analysis showed a progressive pattern of disruption of caudate/thalamus dopaminergic connectivity to hippocampus and amygdala from AD-MCI to AD-DEM stages. This study indicates basal ganglia dopaminergic alterations and connectivity disruption in the nigrostriatal and mesolimbic systems already in early stage AD, extending to several cortico-limbic regions in dementia phases.

AbstractMechanisms underlying the role of diabetes mellitus (DM) as modulator of severity in Parkinson’s Disease (PD) remain unclear. Aim of this study was to investigate the impact of DM on nigrostriatal dopaminergic vulnerability considering two independent cohorts of drug-naïve PD patients (PPMI and DNA studies). Patients with and without DM were first compared and then matched for age, sex, symptoms severity. Differences in123I-FP-CIT binding and molecular connectivity alterations were tested in PD with and without DM within the nigrostriatal pathway. 269 drug-naïve patients were enrolled (PPMI, n=174; DNA, n=95). In both cohorts, patients with DM were older, predominantly male, and exhibited worse non-motor and cognitive symptoms. After severity-matching, patients with DM were found to exhibit more preserved dopamine binding in striatal regions compared to those without DM, together with a lower neural reserve. Patients with DM showed significant dopaminergic connectivity alterations (20%), primarily due to a loss of connectivity (98%). In contrast, patients without DM had more widespread connectivity changes (33%), characterized by both loss (84%) and gained connections (16%). These findings suggest that diabetes directly affects the nigrostriatal network, resulting in less deficits despite similar disease severity, perhaps decreasing the effect of reserve on dopaminergic neurons loss.

AbstractMethodsThis study assessed data from two cohorts of patients with alpha‐synucleinopathies (University of Brescia and University of Rome Tor‐Vergata cohorts). Consecutive participants with video‐polysomnography‐confirmed iRBD, Parkinson's disease (PD), dementia with Lewy bodies (DLB) and controls underwent neurological, clinical and 123I‐FP‐CIT SPECT imaging assessments. Individuals with iRBD were longitudinally monitored to collect clinical phenoconversion to PD or DLB. The main outcome was to identify whole brain 123 I‐FP‐CIT SPECT measures reflecting monoaminergic deficits in each clinical group as compared to controls.ResultsThe cohort (n = 184) included 45 patients with iRBD, 47 PD, 42 DLB and 50 age‐matched controls. Individuals with iRBD were categorized as RBD‐DAT− (n = 32) and RBD‐DAT+ (n = 13), according to nigrostriatal assessment used in clinical practice. Compared to controls, RBD‐DAT− showed an early involvement of the left insula, which increased in RBD‐DAT+, and was present in patients with Parkinson's disease and dementia with Lewy bodies. Longitudinal cox regression analyses revealed a higher risk of phenoconversion in individuals with iRBD and insular monoaminergic deficits [HR = 3.387; CI 95%: 1.18–10.27].InterpretationIn this study, altered insular monoaminergic binding in iRBD was associated with phenoconversion to DLB or PD. These findings may provide a helpful stratification approach for future pharmacological or non‐pharmacological interventions.

INTRODUCTION:The impairment of nigrostriatal dopaminergic network is a core feature of dementia with Lewy bodies (DLB). The involvement and reconfiguration of extranigrostriatal dopaminergic circuitries in the DLB continuum is still theme of debate. We aim to investigate in vivo the dynamic changes of local and long-distance dopaminergic networks across DLB continuum.METHODS:Forty-nine patients (including 29 with dementia and 20 prodromal cases) and fifty-two controls entered the study. Each subject underwent a standardized clinical and neurological examination and performed Brain SPECT to measuring brain dopamine transporter (DAT) density. Spatially normalized images underwent the occipital-adjusted specific binding to obtain parametric data. The ANCOVA was applied to assess 123I-FP-CIT differences between pDLB, overt-DLB and CG, considering age, gender, and motor impairment as variables of no interest. Between-nodes correlation analysis measured molecular connectivity within the ventral and dorsal dopaminergic networks.RESULTS:Prodromal DLB and DLB patients showed comparable nigrostriatal deficits in basal ganglia regions compared with CG. Molecular connectivity analyses revealed extensive connectivity losses, more in ventral than in dorsal dopaminergic network in DLB dementia. Conversely, the prodromal group showed increased connectivity compared to CG, mostly putamen-thalamus-cortical and striatal-cortical connectivity.CONCLUSIONS:This study indicates a comparable basal ganglia deficit in nigrostriatal projections in DLB continuum and supports a different reorganization of extra-striatal dopaminergic connectivity in the prodromal phases of DLB. The shift from an increased to a decreased bilateral putamen-thalamus-cortex connectivity might be a hallmark of transition from prodromal to dementia DLB stages.

This paper describes the evolution of nuclear cardiology techniques in the setting of acute coronary syndromes. Since the 1970s, the contribution of nuclear cardiology has been fundamental in delineating the physiopathology and diagnosis of acute myocardial infarction, when electrocardiogram (ECG) did not provide the diagnosis and when cardiac enzyme assessments were at a very early stage. In this clinical situation, at that time the role of pyrophosphate scintigraphy and antimyosin antibodies was important in ensuring diagnostic precision. However, these methods showed limitations and were abandoned in the late 80s and early 90s when therapeutic applications such as thrombolytic therapy, and primary-and rescue-percutaneous coronary intervention (PCI) were introduced. Beginning in the mid-80s, the introduction and widespread use of perfusion tracers such as 99mTc labelled compounds and technological advances such as SPECT, allowed to assess the efficacy of thrombolysis and early revascularization, as well as to assess in depth myocardial salvage. Currently, perfusion SPECT, especially using fast imaging techniques and dedicated cardiac SPECT with solid-state detectors, allows a quick confirmation or exclusion of acute coronary syndromes, particularly in low-to-intermediate likelihood of coronary artery disease (CAD), especially when there are absolute or relative contraindications to the use of coronary computed tomographic angiography (CCTA).

IntroductionBrain hypometabolism patterns have been previously associated with cognitive decline in Parkinson's disease (PD). Our aim is to evaluate the impact of single-subject fluorodeoxyglucose (FDG)-PET brain hypometabolism on long-term cognitive and motor outcomes in PD.MethodsForty-nine non-demented PD patients with baseline brain FDG-PET data underwent an extensive clinical follow-up for 8 years. The ability of FDG-PET to predict long-term cognitive and motor progression was evaluated using Cox regression and mixed ANCOVA models.ResultsParticipants were classified according to FDG-PET pattern in PD with typical (n = 26) and atypical cortical metabolism (n = 23). Patients with atypical brain hypometabolic patterns showed higher incidence of dementia (60% vs 3%; HR = 18.3), hallucinations (56% vs 7%, HR = 7.3) and faster motor decline compared to typical pattern group.ConclusionThis study argues for specific patterns of FDG-PET cortical hypometabolism in PD as a prognostic marker for long term cognitive and motor outcomes at single-subject level.

Brain imaging can reveal specific characteristics of Cognitive Impairment (CI) related to neurotoxicant exposure. Unique brain characteristic patterns of CI have been revealed among World Trade Center (WTC) responders to the 9/11 terrorist attack, compared to other signatures, including Alzheimer's Disease (AD). Diffuse brain atrophy, reduced cortical thickness and hippocampal subfield volume analyses suggest that reductions in specific subregions are specifically associated with the duration of WTC exposure. These findings support the hypothesis that WTC exposure to neurotoxicants and intense psychological trauma are causing long-term neurodegenerative impacts. The neuro-phenotype of this impairment is distinct from the AD and inconsistent with signatures developed for other known neurodegenerative diseases. The World Trade Center Cognitive Impairment (WTC-CI) may be a WTC-specific encephalopathy with an unknown etiology characterized by widespread cortical atrophy. Applying similar brain imaging modalities, a diffuse brain deposition of fibrillar amyloid-β (Aβ) peptide was observed among ferroalloy workers with prolonged occupational exposure to manganese. These two case studies provide further evidence of how modern brain imaging can improve understanding of relevant mechanisms of neurotoxicity after long term exposure to neurotoxicants.

AD diagnosis rarely relays on a pathophysiological marker in memory centers requiring procedure standardisation for real world diagnostic work up. To study the epidemiology of prodromal and mild stages of AD patients who are eligible for clinical trials with disease modifying therapies.

Preclinical and pathology evidence suggests an involvement of brain dopamine (DA) circuitry in Alzheimer’s disease (AD). We in vivo investigated if, when, and in which target regions [123I]FP-CIT-SPECT regional binding and molecular connectivity are damaged along the AD course. We retrospectively selected 16 amyloid-positive subjects with mild cognitive impairment due to AD (AD-MCI), 22 amyloid-positive patients with probable AD dementia (AD-D), and 74 healthy controls, all with available [123I]FP-CIT-SPECT imaging. We tested whether nigrostriatal vs. mesocorticolimbic dopaminergic targets present binding potential loss, via MANCOVA, and alterations in molecular connectivity, via partial correlation analysis. Results were deemed significant at p < 0.05, after Bonferroni correction for multiple comparisons. We found significant reductions of [123I]FP-CIT binding in both AD-MCI and AD-D compared to controls. Binding reductions were prominent in the major targets of the ventrotegmental-mesocorticolimbic pathway, namely the ventral striatum and the hippocampus, in both clinical groups, and in the cingulate gyrus, in patients with dementia only. Within the nigrostriatal projections, only the dorsal caudate nucleus showed reduced [123I]FP-CIT binding, in both groups. Molecular connectivity assessment revealed a widespread loss of inter-connections among subcortical and cortical targets of the mesocorticolimbic network only (poor overlap with the control group as expressed by a Dice coefficient ≤ 0.25) and no alterations of the nigrostriatal network (high overlap with controls, Dice coefficient = 1). Local- and system-level alterations of the mesocorticolimbic dopaminergic circuitry characterize AD, already in prodromal disease phases. These results might foster new therapeutic strategies for AD. The clinical correlates of these findings deserve to be carefully considered within the emergence of both neuropsychiatric symptoms and cognitive deficits.

Objective: To compare the predictive accuracy of Medial Temporal Lobe Atrophy (MTLA) measurements, for cognitive decline at two-years follow up in subjects subjective memory impairment (SMI).

OBJECTIVE:This study compared the performance of 18F-Florbetapir PET/CT early acquisitions to 18F-FDG PET/CT. METHODS:We included 12 patients who underwent 18F-FDG PET/CT and a dual-time 18F-Florbetapir PET/CT (1-6 min early-scan and 50 min late-scan). PET/CT were analyzed visually by three nuclear medicine physicians with different experience using a four-point scale (0 = no reduction, 1 = slight, 2 = moderate, 3 = severe reduction) for 18F-Florbetapir early-phase and 18F-FDG images in 10 cortical regions (bilateral frontal, temporal, parietal, occipital, posterior cingulate/precuneus), and 18F-Florbetapir late-phase in the same cortical regions using a three-point scale (0 = normal, 1 = abnormal with minor plaques, 2 = abnormal with major plaques). We used SPM12 for semiquantitative analysis applying a ROI-based correlation analysis (considering precuneus as target region and normalized for the mean global binding), a covariance-analysis taking precuneus as target and a comparison of global DMN (default mode network). RESULTS:Inter-reader agreement was high (Cohen's kappa 0.762 for 18F-FDG, 0.775 for 18F-Florbetapir early-phase and 0.794 for late-phase). Regional visual scores of early-phase and 18F-FDG were significantly correlated (ρ = 0.867). Also ROI-based analysis, global brain visual analysis and DMN comparison revealed concordant results, especially at parietal and precuneus (p < 0.001). CONCLUSIONS:18F-Florbetapir early-phase scans significantly correlate on quantitative and visual images with 18F-FDG-PET/CT scans, suggesting that amyloid tracer could be instead of 18F-FDG.

To develop and validate a semi-quantification method (time-delayed ratio, TDr) applied to amyloid PET scans, based on tracer kinetics information. The TDr method requires two static scans per subject: one early (~ 0–10 min after the injection) and one late (typically 50–70 min or 90–100 min after the injection, depending on the tracer). High perfusion regions are delineated on the early scan and applied onto the late scan. A SUVr-like ratio is calculated between the average intensities in the high perfusion regions and the late scan hotspot. TDr was applied to a naturalistic multicenter dataset of 143 subjects acquired with [18F]florbetapir. TDr values are compared to visual evaluation, cortical–cerebellar SUVr, and to the geometrical semi-quantification method ELBA. All three methods are gauged versus the heterogeneity of the dataset. TDr shows excellent agreement with respect to the binary visual assessment (AUC = 0.99) and significantly correlates with both validated semi-quantification methods, reaching a Pearson correlation coefficient of 0.86 with respect to ELBA. TDr is an alternative approach to previously validated ones (SUVr and ELBA). It requires minimal image processing; it is independent on predefined regions of interest and does not require MR registration. Besides, it takes advantage on the availability of early scans which are becoming common practice while imposing a negligible added patient discomfort.

ABSTRACT:Balint syndrome is a rare neurological disorder characterized by simultanagnosia, optic ataxia, and ocular apraxia, and its etiology can be very heterogeneous. Diagnosis is based on neuropsychological evaluation, but brain radiological and nuclear medicine imaging also plays an important role. Because few case reports have been published in literature, in this work, we present 2 patients affected by Balint syndrome in which 18F-FDG PET/CT helped in the diagnosis and follow-up.