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64 The Biomarker-Based Etiological Diagnosis of Neurocognitive Disorders: the European Inter-Societal Delphi Consensus
- Roy P.C. Kessels, Stefano Cappa, Cristina Festari, Matteo Cotta-Ramusino, Federico Massa, Stefania Orini, Flavio Nobili, Giovanni B. Frisoni, for the European Inter-Societal Consensus on the Biomarker-Based Diagnosis of Dementia
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 268-269
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Objective:
In the field of neurocognitive disorders, the perspective offered by new disease-modifying therapy increases the importance of etiological diagnosis. The prescription of cerebrospinal fluid analysis (CSF) and imaging biomarkers is a common practice in the clinic but is often driven more by personal expertise and local availability of diagnostic tools than by evidence of efficacy and cost-effectiveness analysis. This leads to a widely heterogeneous dementia care across Europe. Therefore, a European initiative is currently being conducted to establish a consensus for biomarker-based diagnosis of patients with mild cognitive impairment (MCI) and mild dementia.
Participants and Methods:Since November 2020, a European multidisciplinary task force of 22 experts from 11 scientific societies have been defining a diagnostic workflow for the efficient use of biomarkers. The Delphi consensus procedure was used to bridge the gaps of incomplete scientific evidence on biomarker prioritization. The project has been in two phases. During Phase 1, we conducted a literature review on the accuracy of imaging, CSF, neurophysiological and blood biomarkers in predicting the clinical progression or in defining the underpinning aetiology of main neurocognitive disorders. Evidence was provided to support the panelists’ decisions. In phase 2, a modified Delphi procedure was implemented, and consensus was reached at a threshold of 70% agreement, or 50%+1 when a question required rediscussion.
Results:In phase 1, 167 out of 2,200 screened papers provided validated measures of biomarker diagnostic accuracy compared with a gold standard or in predicting progression or conversion of MCI to the dementia stage (i.e., MRI, CSF, FDG-PET, DaT-imaging, amyloid-PET, tau-PET, and myocardial MIBG-scintigraphy and EEG). During phase 2, panelists agreed on the clinical workspace of the workflow, the stage of application, and the patient age window. The workflow is patient-centered and features three levels of assessment (W): W1 defines eleven clinical profiles based on integrated results of neuropsychology, MRI atrophy patterns, and blood tests; W2 describes the first-line biomarkers according to W1 versus clinical suspicion; and W3 suggests the second-line biomarkers when the results of first-line biomarkers are inconsistent with the diagnostic hypothesis, uninformative or inconclusive. CSF biomarkers are first-line in the suspect of Alzheimer’s disease (AD) and when inconsistent neuropsychological and MRI findings hinder a clear diagnostic hypothesis; dopamine SPECT/PET for those leading to suspect Lewy body spectrum. FDG-PET is first-line for the clinical profiles leading to suspect frontotemporal lobar degeneration and motor tauopathies and is followed by CSF biomarkers in the case of atypical metabolic patterns, when an underlying AD etiology is conceivable.
Conclusions:The workflow will promote consistency in diagnosing neurocognitive disorders across countries and rational use of resources. The initiative has some limitations, mainly linked to the Delphi procedure (e.g., kickoff questions were driven by the moderators, answers are driven by the Delphi panel composition, a subtle phrasing of the questions may drive answers, and 70% threshold for convergence is conventional). However, the diagnostic workflow will be able to help clinicians achieve an early and sustainable etiological diagnosis and enable the use of disease-modifying drugs as soon as they become available.
Grouping for behavioral and psychological symptoms in dementia: clinical and biological aspects. Consensus paper of the European Alzheimer disease consortium
- Philippe H. Robert, Frans R.J. Verhey, E. Jane Byrne, Catherine Hurt, Peter Paul De Deyn, Flavio Nobili, Roberta Riello, Guido Rodriguez, Giovanni B. Frisoni, Magda Tsolaki, Nora Kyriazopoulou, Roger Bullock, Alistair Burns, Bruno Vellas
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- Journal:
- European Psychiatry / Volume 20 / Issue 7 / November 2005
- Published online by Cambridge University Press:
- 16 April 2020, pp. 490-496
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Behavioral and psychological symptoms of dementia (BPSD), constitute a major clinical component of Alzheimer’s disease (AD). There is a growing interest in BPSD as they are responsible for a large share of the suffering of patients and caregivers, and they strongly determine the patient’s lifestyle and management. Better detection and understanding of these symptoms is essential to provide appropriate management. This article is a consensus produced by the behavioral group of the European Alzheimer’s Disease Consortium (EADC). The aim of this article is to present clinical description and biological correlates of the major behavioral and psychological symptomatology in AD. BPSD is not a unitary concept. Instead, it should be divided into several symptoms or more likely: groups of symptoms, each possibly reflecting a different prevalence, course over time, biological correlate and psychosocial determinants. There is some clinical evidence for clusters within groups of BPSD. Biological studies indicate that patients with AD and BPSD are associated with variations in the pathological features (atrophy, brain perfusion/metabolism, histopathology) when compared to people with AD without BPSD. An individually tailored approach taking all these aspects into account is warranted as it may offer more, and better, pharmacological and non-pharmacological treatment opportunities.
Mitochondrial Function Is Related to Alterations at Brain SPECT in Depressed Patients
- Ann Gardner, Dario Salmaso, Davide Nardo, Federica Micucci, Flavio Nobili, Alejandro Sanchez-Crespo, Hans Jacobsson, Stig A. Larsson, Marco Pagani
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- CNS Spectrums / Volume 13 / Issue 9 / September 2008
- Published online by Cambridge University Press:
- 07 November 2014, pp. 805-814
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Introduction: 99mTc-d,I-hexamethylpropylene amine oxime (99m Tc-HMPAO) retention in brain is proportional to cerebral blood flow and related to both the local hemodynamic state and to the cellular content of reduced glutathione. Alterations of the regional distribution of 99mTc-HMPAO retention, with discrepant results, have been reported at functional brain imaging of unipolar depression. Since mitochondrial involvement has been reported in depressed patients, the aim of the study was to explore whether the 99mTc-HMPAO retention at single-photon emission computed tomography in depressed patients may relate to different levels of mitochondrial function.
Methods: All patients had audiological and muscular symptoms, somatic symptoms that are common in depression. Citrate synthase (CS) activity assessed in muscle mitochondria correlated strongly with the activities of three mitochondrial respiratory chain enzymes and was used as a marker of mitochondrial function. K-means clustering performed on CS grouped eight patients with low and 11 patients with normal CS. Voxel-based analysis was performed on the two groups by statistical parametric mapping.
Results: Voxel-based analysis showed significantly higher 99mTc-HMPAO retention in the patients with low CS compared with the patients with normal CS in the posterior and inferior frontal cortex, the superior and posterior temporal cortex, the somato-sensory cortex, and the associative parietal cortex.
Conclusion: Low muscle CS in depressed patients is related to higher regional 99mTc-HMPAO retention that may reflect cerebrovascular adaptation to impaired intracellular metabolism and/or intracellular enzymatic changes, as previously reported in mitochondrial disorder. Mitochondrial dysfunction in varying proportions of the subjects may explain some of the discrepant results for 99mTc-HMPAO retention in depression.
Assessment of dementia in ethnic minority patients in Europe: a European Alzheimer's Disease Consortium survey
- T. Rune Nielsen, Asmus Vogel, Matthias W. Riepe, Alexandre de Mendonça, Guido Rodriguez, Flavio Nobili, Anders Gade, Gunhild Waldemar
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- Journal:
- International Psychogeriatrics / Volume 23 / Issue 1 / February 2011
- Published online by Cambridge University Press:
- 06 July 2010, pp. 86-95
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Background: In most European countries the ethnic minority migrant populations are currently reaching an age where dementia becomes an increasingly important issue. There is no European consensus on good clinical practice with these patient groups, who often have special needs and expectations with regard to dementia services.
Methods: A survey was conducted in clinical dementia centers in 15 European countries. Questionnaires focusing on different points in the clinical assessment of dementia in ethnic minority patients were mailed to leading dementia experts of the European Alzheimer's Disease Consortium.
Results: Thirty-six centers from 15 countries responded to the survey. Ethnic minority patients were seen on a regular basis in 69% of these centers. The diagnostic evaluation was in accordance with evidence-based clinical guidelines in 84–100% of the centers, but most centers performed cognitive assessment with instruments that are only validated in Western cultures and frequently relied on family members for interpretation. Diagnostic evaluation of the patients was considered to be challenging in 64% of the centers, mainly because of communication problems and lack of adequate assessment tools. In general, there were few indicators of culturally sensitive dementia services in the centers.
Conclusions: Ethnic minority patients are seen on a regular basis in European dementia clinics. Assessment of such patients is difficult for a number of reasons. Results from this study show that the most challenging issues are communication problems and assessment of cognitive function where there is a need to develop specific tests for ethnic minority patients.