Finding our way through the labyrinth of dementia biomarkers

Abstract

In 1984, consensual criteria for Alzheimer’s disease (AD) were published, which were fully based on symptoms as tracked by clinical and neuropsychological examinations [1]. More than 20 years later, revised criteria have been proposed, progressively integrating biomarkers, until 2018 when the newly proposed research criteria exclusively relied on biomarkers [2–4]. This shift from one extreme to the other has been controversial [5]. Wherever we stand in this debate, it must be acknowledged that early diagnosis of neurodegeneration as well as reliable etiological diagnosis of the causes underlying cognitive decline remains challenging on the basis of merely clinical assessment. Biomarkers have demonstrated great value in that respect and, accordingly, they are playing an increasing role. There is also general agreement that combining biomarkers improves diagnostic accuracy [6, 7]. Consequently, biomarker development is booming, broadening the spectrum of available modalities (magnetic resonance imaging (MRI), positon emission tomography (PET), cerebrospinal fluid (CSF), upcoming blood biomarkers), and the pathologies to be assessed (neurodegeneration, amyloid, tau αsynuclein, neuroinflammation, synaptic density, etc.) (Fig. 1). However, faced with this arsenal of biomarkers, uncertainty has arisen regarding appropriate combination and/or order in which these biomarkers should be used in diagnostic evaluations. In an article published as a Personal View in the Lancet Neurology in November 2020 [8], we thus proposed a diagnostic algorithm aiming at providing consensus recommendations for the optimal ordering of the most validated biomarkers into meaningful sequences depending on the clinical presentation. This article was the end result of intensive debates and discussions from a multidisciplinary group of experts and opinion leaders from all over the world, comprised of nuclear medicine physicians, radiologists, neurologists, geriatricians, psychiatrists, clinical and basic neuroscientists, and patient-advocates, whomet January 30–February 2, 2019, in Cannes (France) under the auspices of the European Association of Nuclear Medicine (EANM) to discuss the current role and the future potential of PET neuroimaging in dementia. The members of the EANM Neuroimaging