9 General introduction Subjective cognitive decline In 2014, the Subjective Cognitive Impairment Cohort (SCIENCe project) started at the Alzheimer Center Amsterdam, which studies individuals with SCD (Box 1)(8). Individuals with SCD are cognitively normal (i.e. performance on cognitive tests within normal limits) with a self-perceived (subjective) decline in any cognitive domain over time (7, 9). SCD can be caused by (a combination of) many different factors, such as depressive symptoms, sleeping disorders, stress-inducing life events or normal aging, making it a heterogeneous group of individuals. SCD could also be the first symptom of a neurodegenerative disease, most frequently AD. Since the pathogenesis of AD is a gradual process and accumulation of pathology starts decades before diagnosis of dementia, some cognitively normal individuals with SCD could already harbor the first pathological changes associated with this disease. As these subjects are difficult to identify, several so-called SCD plus clinical criteria have been proposed that are thought to increase the likelihood of a neurodegenerative disease in individuals with SCD. These include the self-perceived decline in memory rather than other domains of cognition, the onset of SCD within the last five years, age of onset ≥ 60 year, worries associated with SCD, feeling of worse cognitive performance than peers, confirmation of SCD by an informant and the presence of the APOE ε4 genotype (7). Individuals with SCD included in the SCIENCe project have presented to a memory clinic because of cognitive complaints, which makes them a clinically relevant population. They are searching for information about their biomarkers status and risk of progression to dementia, but it is often difficult for clinicians to provide answers, since these are largely unknown yet. ATN classification Over the past decade, there has been a change in the way AD is viewed by clinicians and researchers. Before availability of biomarkers, AD could only be diagnosed definitively after death by neuropathological examination, while a probable diagnosis in vivo relied mostly on clinical symptoms(2). Over the past decade, biomarker research has expanded greatly and many measures have become available that correlate well with neuropathology. This enables a biological approach for AD, which also helps to conduct studies aimed at a better understanding of the pathophysiological disease trajectories. It will furthermore benefit the search for therapeutic targets, since disease-modifying interventions must be focused on a biological target. In 2018, a new research framework was developed under the auspices of the National Institute on Aging and Alzheimer’s Association (NIA-AA) which groups biomarkers into three categories (ATN) (10). With this framework, the definition of AD was shifted from 1