28 Chapter 2 RESULTS Baseline demographics and clinical features At baseline, the 693 SCD participants were on average 60±9 years old, 283(41%) were female, and MMSE was 28±2. With 385 (56%) participants, the majority of the participants was negative for each of the three biomarkers (A-T-N-, normal AD biomarkers). Figure 1 and Table 1 show the distribution, demographics and clinical characteristics of all biomarker profiles (three category comparison provided in Supplemental Table e-1, available from Dryad: bg79cnp71). Participants were older in A+ profiles and in profiles with a higher number of biomarkers affected. There were no significant differences in sex, education, MMSE or GDS scores between ATN profiles. APOE ε4 varied by ATN biomarker profiles, with A+ profiles containing the highest number of APOE ε4 carriers. Comparing biomarker values between ATN profiles, we found that total-tau (not included in our ATN-definition) was lowest in A-T-N-, and was higher in T+ groups, but not in N+ groups. P-tau and total-tau strongly correlated with each other (Spearman’s rho 0.90, p≤0.00). GCA scores were higher in N+ profiles (Spearman’s rho MTA~GCA: 0.35, p≤0.00). There was no difference in any of the MRI measures of small vessel disease between groups. Participants in the control group without SCD were on average 9 years older than our SCD sample and more often female (52% versus 41%, (Supplemental Table e-2, available from Dryad: The distribution of ATN profiles differed between the two cohorts (p=0.00). The prevalence of A-T-N- was similar in both cohorts, but N+ biomarker profiles were more prevalent in the control group (23% versus 11%), while the A+ was somewhat more common in our SCD sample (18% versus 14%). In the control group, age differed across ATN profiles, with on visual inspection a stronger age effect than in the SCD sample. ATN profiles also differed on MMSE.