Clinical utility of FDG PET in Parkinson's disease and atypical parkinsonism associated with dementia

PURPOSE: There are no comprehensive guidelines for the use of FDG PET in the following three clinical scenarios: (1) diagnostic work-up of patients with idiopathic Parkinson's disease (PD) at risk of future cognitive decline, (2) discriminating idiopathic PD from progressive supranuclear palsy, and (3) identifying the underlying neuropathology in corticobasal syndrome. METHODS: We therefore performed three literature searches and evaluated the selected studies for quality of design, risk of bias, inconsistency, imprecision, indirectness and effect size. Critical outcomes were the sensitivity, specificity, accuracy, positive/negative predictive value, area under the receiving operating characteristic curve, and positive/negative likelihood ratio of FDG PET in detecting the target condition. Using the Delphi method, a panel of seven experts voted for or against the use of FDG PET based on published evidence and expert opinion. RESULTS: Of 91 studies selected from the three literature searches, only four included an adequate quantitative assessment of the performance of FDG PET. The majority of studies lacked robust methodology due to lack of critical outcomes, inadequate gold standard and no head-to-head comparison with an appropriate reference standard. The panel recommended the use of FDG PET for all three clinical scenarios based on nonquantitative evidence of clinical utility. CONCLUSION: Despite widespread use of FDG PET in clinical practice and extensive research, there is still very limited good quality evidence for the use of FDG PET. However, in the opinion of the majority of the panellists, FDG PET is a clinically useful imaging biomarker for idiopathic PD and atypical parkinsonism associated with dementia

Diagnostic utility of FDG-PET in the differential diagnosis between different forms of primary progressive aphasia

PURPOSE: A joint effort of the European Association of Nuclear Medicine (EANM) and the European Academy of Neurology (EAN) aims at clinical guidance for the use of FDG-PET in neurodegenerative diseases. This paper addresses the diagnostic utility of FDG-PET over clinical/neuropsychological assessment in the differentiation of the three forms of primary progressive aphasia (PPA). METHODS: Seven panelists were appointed by the EANM and EAN and a literature search was performed by using harmonized PICO (Population, Intervention, Comparison, Outcome) question keywords. The studies were screened for eligibility, and data extracted to assess their methodological quality. Critical outcomes were accuracy indices in differentiating different PPA clinical forms. Subsequently Delphi rounds were held with the extracted data and quality assessment to reach a consensus based on both literature and expert opinion. RESULTS: Critical outcomes for this PICO were available in four of the examined papers. The level of formal evidence supporting clinical utility of FDG-PET in differentiating among PPA variants was considered as poor. However, the consensual recommendation was defined on Delphi round I, with six out of seven panelists supporting clinical use. CONCLUSIONS: Quantitative evidence demonstrating utility or lack thereof is still missing. Panelists decided consistently to provide interim support for clinical use based on the fact that a typical atrophy or metabolic pattern is needed for PPA according to the diagnostic criteria, and the synaptic failure detected by FDG-PET is an earlier phenomenon than atrophy. Also, a normal FDG-PET points to a non-neurodegenerative cause

Medial temporal lobe atrophy and posterior atrophy scales normative values

OBJECTIVES: The medial temporal lobe atrophy (MTA) and the posterior atrophy (PA) scales allow to assess the degree hippocampal and parietal atrophy from magnetic resonance imaging (MRI) scans. Despite reliable, easy and widespread employment, appropriate normative values are still missing. We aim to provide norms for the Italian population. // METHODS: Two independent raters assigned the highest MTA and PA score between hemispheres, based on 3D T1-weighted MRI of 936 Italian Brain Normative Archive subjects (age: mean ± SD: 50.2 ± 14.7, range: 20-84; MMSE>26 or CDR = 0). The inter-rater agreement was assessed with the absolute intraclass correlation coefficient (aICC). We assessed the association between MTA and PA scores and sociodemographic features and APOE status, and normative data were established by age decade based on percentile distributions. // RESULTS: Raters agreed in 90% of cases for MTA (aICC = 0.86; 95% CI = 0.69-0.98) and in 86% for PA (aICC = 0.82; 95% CI = 0.58-0.98). For both rating scales, score distribution was skewed, with MTA = 0 in 38% of the population and PA = 0 in 52%, while a score ≥ 2 was only observed in 12% for MTA and in 10% for PA. Median denoted overall hippocampal (MTA: median = 1, IQR = 0-1) and parietal (PA: median = 0, IQR = 0-1) integrity. The 90th percentile of the age-specific distributions increased from 1 (at age 20-59) for both scales, to 2 for PA over age 60, and up to 4 for MTA over age 80. Gender, education and APOE status did not significantly affect the percentile distributions in the whole sample, nor in the subset over age 60. // CONCLUSIONS: Our normative data for the MTA and PA scales are consistent with previous studies and overcome their main limitations (in particular uneven representation of ages and missing percentile distributions), defining the age-specific norms to be considered for proper brain atrophy assessment

European consensus for the diagnosis of MCI _QUADAS-II assessment

Using a modified Delphi procedure, a European task force is defining a diagnostic workflow for etiologicical and biomarker-based diagnosis of neurocognitive disorders, in which expert expertise fills evidence gaps for validity and prioritization of biomarkers. The panel of experts is asked to answer a Delphi questionnaire and justify their answers with evidence from the literature. We then provided the experts with data on the diagnostic accuracy of biomarkers (MRI, amyloid PET, tau and FDG, MIBG scintigraphy, DaT-SPECT, EEG and polysomnography) in predicting clinical progression from prodromal stages to mild dementia in neurocognitive disorders. We assessed the quality of evidence from the included literature using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). The data were recorded in the attached Excel sheet.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

European consensus for the diagnosis of MCI and mild dementia: Preparatory phase

Introduction: Etiological diagnosis of neurocognitive disorders of middle-old age relies on biomarkers, although evidence for their rational use is incomplete. A European task force is defining a diagnostic workflow where expert experience fills evidence gaps for biomarker validity and prioritization. We report methodology and preliminary results. Methods: Using a Delphi consensus method supported by a systematic literature review, 22 delegates from 11 relevant scientific societies defined workflow assumptions. Results: We extracted diagnostic accuracy figures from literature on the use of biomarkers in the diagnosis of main forms of neurocognitive disorders. Supported by this evidence, panelists defined clinical setting (specialist outpatient service), application stage (MCI-mild dementia), and detailed pre-assessment screening (clinical-neuropsychological evaluations, brain imaging, and blood tests). Discussion: The Delphi consensus on these assumptions set the stage for the development of the first pan-European workflow for biomarkers' use in the etiological diagnosis of middle-old age neurocognitive disorders at MCI-mild dementia stages. Highlights: Rational use of biomarkers in neurocognitive disorders lacks consensus in Europe. A consensus of experts will define a workflow for the rational use of biomarkers. The diagnostic workflow will be patient-centered and based on clinical presentation. The workflow will be updated as new evidence accrues

Do Beliefs about the Pathogenetic Role of Amyloid Affect the Interpretation of Amyloid PET in the Clinic.

Beliefs of dementia experts about the pathogenic role of amyloid in Alzheimer's disease (AD) may affect the use of amyloid positron emission tomography (PET)

Comparison of visual criteria for amyloid-pet reading: Could criteria merging reduce inter-rater variability?

BACKGROUND: Three different amyloid tracers labeled with 18-flourine have been introduced into clinical use. The leaflets of tracers indicate different visual criteria for PeT reporting. in clinical practice, it is not yet ascertained whether these criteria are equivalent in terms of diagnostic accuracy or if anyone is better than another. We aimed to evaluate the inter and intra-rater variability of visual assessment of 18f-florbetapir PeT/ cT images among six independent readers with different clinical experience. MeThodS: We analyzed 252 PeT/cT scans, visually assessed by each reader three times, applying independently the three different reading criteria proposed. each reader evaluated the regional uptake specifying for each cortical region a numeric value of grading of positivity in order to assign a final score. At the end of each reading a level of confidence was determined by assigning a score from 0 (negative) to 4 (positive). After first reading, those cases in which the evaluations by two experienced readers did not match (discordant cases) were independently reevaluated merging all the three different visual interpretation criteria. RESULTS: Good agreement was observed for visual interpretation among the six readers' confidence-level using independently the three visual reading criteria: icc=0.83 (0.80-0.86) for 18F-florbetapir, ICC=0.84 (0.81-0.87) for 18F-florbetaben, and ICC=0.86 (0.83-0.88) for 18F-flute-metamol reading. A good inter-rater agreement was observed for final-score too: ICC=0.74 (0.70-0.78) for 18F-florbetapir; ICC=0.82 (0.79-0.85) for 18F-florbetaben; ICC=0.84 (0.81-0.87) for 18F-flutemetamol. Intra-rater agreement was good for final-score (from 0.76 to 0.90; P<0.001) and confidence-level (Spearman's rho from 0.89 to 1.00; P<0.001). Disagreement between the two experienced readers was observed in 22 of 252 cases (9%). The agreement converged over a second round of independent reading in 12 of 22 cases (54%), by merging all the criteria. concluSionS: all the criteria proposed are useful to determine the grading of positivity or negativity of amyloid deposition and their merging improves the diagnostic confidence and provides a better agreement

Assessing FDG-PET diagnostic accuracy studies to develop recommendations for clinical use in dementia

BACKGROUND: FDG-PET is frequently used as a marker of synaptic damage to diagnose dementing neurodegenerative disorders. We aimed to adapt the items of evidence quality to FDG-PET diagnostic studies, and assess the evidence available in current literature to assist Delphi decisions for European recommendations for clinical use. METHODS: Based on acknowledged methodological guidance, we defined the domains, specific to FDG-PET, required to assess the quality of evidence in 21 literature searches addressing as many Population Intervention Comparison Outcome (PICO) questions. We ranked findings for each PICO and fed experts making Delphi decisions for recommending clinical use. RESULTS: Among the 1435 retrieved studies, most lacked validated measures of test performance, an adequate gold standard, and head-to-head comparison of FDG-PET and clinical diagnosis, and only 58 entered detailed assessment. Only two studies assessed the accuracy of the comparator (clinical diagnosis) versus any kind of gold-/reference-standard. As to the index-test (FDG-PET-based diagnosis), an independent gold-standard was available in 24% of the examined papers; 38% used an acceptable reference-standard (clinical follow-up); and 38% compared FDG-PET-based diagnosis only to baseline clinical diagnosis. These methodological limitations did not allow for deriving recommendations from evidence. DISCUSSION: An incremental diagnostic value of FDG-PET versus clinical diagnosis or lack thereof cannot be derived from the current literature. Many of the observed limitations may easily be overcome, and we outlined them as research priorities to improve the quality of current evidence. Such improvement is necessary to outline evidence-based guidelines. The available data were anyway provided to expert clinicians who defined interim recommendations

Comparison of Bioinformatics Pipelines and Operating Systems for the Analyses of 16S rRNA Gene Amplicon Sequences in Human Fecal Samples

Amplicon high-throughput sequencing of 16S ribosomal RNA (rRNA) gene is currently the most widely used technique to investigate complex gut microbial communities. Microbial identification might be influenced by several factors, including the choice of bioinformatic pipelines, making comparisons across studies difficult. Here, we compared four commonly used pipelines (QIIME2, Bioconductor, UPARSE and mothur) run on two operating systems (OS) (Linux and Mac), to evaluate the impact of bioinformatic pipeline and OS on the taxonomic classification of 40 human stool samples. We applied the SILVA 132 reference database for all the pipelines. We compared phyla and genera identification and relative abundances across the four pipelines using the Friedman rank sum test. QIIME2 and Bioconductor provided identical outputs on Linux and Mac OS, while UPARSE and mothur reported only minimal differences between OS. Taxa assignments were consistent at both phylum and genus level across all the pipelines. However, a difference in terms of relative abundance was identified for all phyla (p &lt; 0.013) and for the majority of the most abundant genera (p &lt; 0.028), such as Bacteroides (QIIME2: 24.5%, Bioconductor: 24.6%, UPARSE-linux: 23.6%, UPARSE-mac: 20.6%, mothur-linux: 22.2%, mothur-mac: 21.6%, p &lt; 0.001). The use of different bioinformatic pipelines affects the estimation of the relative abundance of gut microbial community, indicating that studies using different pipelines cannot be directly compared. A harmonization procedure is needed to move the field forward