26 Chapter 2 [11C]PIB in older participants (38, 39). 90-minutes dynamic PET emission scans were obtained immediately starting with tracer injection. All scans were visually rated as ‘positive’ or ‘negative’ by a trained nuclear medicine physician. ATN classification We used amyloid PET (n=105) or CSF Aβ (n=588) to determine whether a participant was A- or A+. If both measures were available, the PET result was used. CSF concentrations were considered amyloid positive <813 pg/mL (34). For tau (T), we used CSF p-tau concentrations. Values were considered p-tau positive > 52 pg/ml (40). We used the average MTA to determine neurodegeneration (N). For participants <65 years of age, an average MTA score ≥1 was considered positive, for participants ≥65 years of age, an average MTA score ≥1.5 was considered positive (41). Because a number of ATN profiles only contained very few participants, we also clustered the eight biomarkers profiles into three categories. The A-T-N- profile was labelled as the ‘normal AD biomarker’ category. We clustered the remaining A- profiles (A-T-N+, A-T+N- and A-T+N+) as ‘non-AD pathologic change’ and we clustered all A+ profiles (A+T-N-, A+T-N+, A+T+N-, A+T+N+) as ‘Alzheimer’s continuum’ (1). Control group For comparison, we also included a control group without subjective cognitive decline, recruited from the EMIF-AD PreclinAD study (42). We included 124 participants, including 53 monozygotic twin pairs and 18 singletons. For 119 participants, A was determined by visual read of [18F]Flutemetamol PET. Levels of CSF Aβ 40 and Aβ42, and p-tau were analyzed using kits from ADx Neurosciences/Euroimmun. CSF concentrations were considered amyloid positive when the CSF Aβ42/40 ratio was < 0.065 (n=5 for whom amyloid PET was not available). To determine T, we used the 75th percentile of p-tau ( ≥ 86 pg/mL). N was determined using average MTA ( <65 years - MTA ≥1; ≥65 years - MTA ≥1.5 considered positive). Neuropsychological testing procedures for the control group were largely similar to procedures for participants with SCD. For 121 participants, follow-up assessments were available (2±0 years). Statistics We compared demographic and clinical variables between the eight ATN biomarker profiles. For continuous variables, we used Analysis of Variance (ANOVA) and Kruskal-Wallis where appropriate, and post-hoc Tukey’s test if the assumption for homogeneity of variances was met, and Games-Howell if the assumption was not met. For dichotomous variables we used Fisher’s exact test, and post-hoc looked at