European Inter‐Societal Delphi Consensus for the biomarker‐based etiological diagnosis of neurocognitive disorders in the mild stage
Authors: Massa Federico , Festari Cristina , Ramusino Matteo Cotta , Orini Stefania , Aarsland Dag , Agosta Federica , Babiloni Claudio , Boada Mercè , Borroni Barbara , Cappa Stefano F , Dubois Bruno , Frederiksen Kristian Steen , Frölich Lutz , Garibotto Valentina , Georges Jean , Haliassos Alexander , Hansson Oskar , Jessen Frank , Kamondi Anita , Kessels Roy P.C. , Morbelli Silvia , O'Brien John T , Otto Markus , Perret‐Liaudet Armand , Pizzini Francesca B , Ritchie Craig W. , Scheltens Philip , van der Flier Wiesje M. , Vandenbulcke Mathieu , Vanninen Ritva , Verhey Frans R.J. , Vernooij Meike W , Yousry Tarek , Nobili Flavio , Frisoni Giovanni B 
Published: June 2023

Background

CSF and imaging biomarkers are needed for the etiological diagnosis of neurocognitive disorders, but evidence is incomplete on their rational use in the clinic. Since October 2020, a European task force has been defining an evidence‐based diagnostic workflow, where incomplete evidence is filled by the opinion of experts. Herein, we report the preliminary results through January 2022.

Method

A Delphi method was used to reach consensus. Eleven pertinent European scientific societies delegated two panelists each to join Delphi rounds and voting. Consensus was set at 70% of consistent responses.

Result

In the 5 voting rounds completed so far, panelists defined clinical setting (specialist outpatient service) and stage of application (prodromal and mild dementia) of the workflow, patients’ age window of biomarkers use (strongly encouraged below 70 years and of limited usefulness over 85). Workflow is configurated to be patient‐centered and structured on three levels of assessment (W): W1, definition of clinical profiles based on the combined results of MRI, neuropsychology, blood tests; W2, choice of first‐line biomarkers according to the main clinical suspicion (i.e., FDG‐PET for frontotemporal lobar degeneration and motor tauopathies, dopamine SPECT/PET for Lewy body spectrum disorders, and CSF biomarkers either for Alzheimer’s disease or in cases with inconclusive neuropsychological and/or MRI findings, whereas no biomarker was indicated in suspected vascular cognitive impairment); W3, selection of a second‐line biomarker when results of first‐line biomarkers are inconsistent with diagnostic hypothesis (i.e., not typical FDG‐PET pattern) or uninformative (i.e., borderline CSF amyloid results) or not sufficient to rule out other etiologies (i.e., amyloid‐positive and tau‐negative CSF results) or when a diagnosis remains possible despite a negative first‐line biomarker (e.g., normal dopamine SPECT/PET in suspected prodromal dementia with Lewy bodies).

Conclusion

The task force is currently defining the second‐line biomarkers of W3 and the project it set to deliver the final algorithm by June 2022. The workflow will promote consistency in diagnosing neurocognitive disorders across countries, and rational use of resources. The initiative has an impact in preparing clinicians to work in the upcoming clinical space where etiological disease‐modifying drugs are expected to be available.