23 ATN classification in subjective cognitive decline INTRODUCTION The research framework for Alzheimer’s disease (AD) diagnosis, developed under the auspices of the National institute on Aging and Alzheimer’s Association (NIAAA), proposes to categorize individuals based on biomarker evidence of pathology using the so-called ‘ATN classification’ (1). According to the ATN classification system, each individual is rated for the presence of beta-amyloid (CSF Aβ or amyloid PET, ‘A’), hyperphosphorylated tau (CSF p-tau or tau PET, ‘T’) and neurodegeneration (atrophy on structural MRI, FDG PET or CSF total tau, ‘N’), resulting in eight possible biomarker combinations. Several former studies have applied the ATN classification scheme (2-8). Of these, two have used a cross-sectional design in cognitively unimpaired participants (2, 3), and one focused on biomarker inconsistencies in healthy controls, MCI and dementia patients (4). Three former studies had a longitudinal design, evaluating the association between ATN and cognitive decline in a nondemented elderly (cognitively normal and/or MCI) (5-7). Subjective cognitive decline (SCD) is characterized by self-perceived decline in cognition, but comparable cognitive performance to peers (9, 10). In SCD, abnormal amyloid, abnormal tau and signs of neurodegeneration are associated with an increased risk of cognitive decline (11-17). Longitudinal studies investigating the ATN classification scheme in relation to clinical progression in SCD, which has been described as stage 2 in the diagnostic framework (1), are not yet available. We aimed to examine (i) the distribution and clinical correlates of the ATN biomarker profiles in individuals presenting with SCD at a memory clinic, and (ii) to investigate the ATN predictive value for risk of clinical decline over time. METHODS Population We included 693 participants with SCD from the Amsterdam Dementia Cohort and the ‘Subjective Cognitive Impairment Cohort’ (SCIENCe) project at the Alzheimer Center Amsterdam (18-20). All participants underwent a standardized diagnostic workup, which consisted of a neurological, physical and neuropsychological evaluation, and brain MRI (18, 19). We used the Geriatric Depression Scale (GDS) to assess depressive symptoms (21, 22). Participants were labeled SCD in a multidisciplinary consensus meeting when clinical and cognitive testing was normal and criteria for MCI, dementia 2