108 Chapter 5 METHODS Population We retrospectively studied 829 cognitively normal individuals with SCD from the Amsterdam Dementia Cohort and SCIENCe project (Subjective Cognitive Impairment Cohort) (20). We selected all individuals with a baseline SCD diagnosis with available array genotyping, and availability of either ATN biomarkers, and/or follow-up information. In the selection process, we excluded 113 individuals due to non-European ancestry (population outliers) or due to close family relations, which led to a total sample size 829 individuals (Figure 1). All individuals received a standardized diagnostic workup, which included a medical and neurological investigation, neuropsychological assessment, cerebrospinal fluid (CSF) analysis and brain magnetic resonance imaging (MRI) (20, 21). The Dutch Verhage system is used for the rating of education (22). In a multidisciplinary consensus meeting, individuals received the label of SCD when they were cognitively normal; i.e. there were no formal deficits in cognition according to neuropsychological test scores and criteria for mild cognitive impairment (MCI) or dementia were not met, and when there was no other neurological or psychiatric condition that could cause their cognitive complaints. Eight hundred and seven individuals (97%) had any biomarker available within 1 year of baseline diagnosis (MRI, CSF and/or positron emission tomography (PET)). For 491 individuals (59%), follow-up assessments were available (4±3 years). At followup, clinical diagnoses were re-assessed as SCD, MCI, AD dementia, or other types of dementia (including frontotemporal dementia (FTD), primary progressive aphasia (PPA), vascular dementia, dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and Huntington’s disease) (23-29). For 469 individuals (57%), both followup diagnoses and baseline biomarkers were available. All patients gave written informed consent. The study was approved by the medical ethical committee of the VU University and was in accordance with the Helsinki Declaration of 1975. ATN classification PET, CSF and MRI procedures were similar to our previous study using the ATNclassification in SCD (4). The following sections describe the procedures for the ATN classification in brief. We used amyloid PET or CSF abeta to define A, CSF p-tau to define T, and the medial temporal atrophy score (MTA) on MRI to define N. When both amyloid PET and CSF abeta were available, the PET result was used to define A. We additionally clustered