64 Chapter 3 Statistics We used t-test, Mann-Whitney U and chi-square where appropriate to compare demographic measures between amyloid positive and amyloid negative groups, based on visual assessment. We used Cohen’s kappa to determine the degree of concordance between visual assessment on the one hand, and the six thresholds on the other hand. We used linear mixed models (LMM) to assess the associations between amyloid status (visual and data-driven) and memory slopes. Separate models were run for each of the seven ways of defining amyloid positivity. Amyloid status, time and the interaction between amyloid status and time were included as independent variables, age, sex, education and scanner type were included as covariates, and scores on the RAVLT delayed memory task were used as dependent variables. Intercept and time were included as random factors, as this resulted in a better fit. Using these models, we estimated the annual change over time for both a negative and a positive amyloid status. We compared models based on beta’s, p-values and Akaike Information Criterion (AIC). Subsequently, using an increasing number of quantiles, we divided the sample into two, three, four and five equal-sized distributions (i.e. subgroups) to explore whether there is a gradual association between amyloid burden and memory slope. We subsequently used LMM to estimate memory slopes for each subgroup. Separate analyses were run for each quantile-based division. Subgroups (entered as dummies), time and the interaction between subgroups and time were included as independent variables, age, sex, education and scanner type were included as covariates, and RAVLT delayed recall score was used as dependent variable. In addition, we ran models including subgroups as continuous variables, and present the resulting p-value for trend. All analyses were done using SPSS version 26 and R studio version 1.1.463. For the estimated trends we used the R studio function of emtrends. P-values <0.05 were considered significant. RESULTS Baseline demographics At baseline, individuals were on average 64±8 years old, 63 (39%) were female, and MMSE was 29±1 (Table 1). Among 162 individuals, 38 (24%) were amyloid positive as defined by visual assessment. Amyloid positive (A+) individuals were on average older and more often APOE ε4 carrier than amyloid negative (A-) individuals.
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