2.10. Data analysis

Statistical analyses were performed with SPSS, version 20.0 for the Macintosh.

Linear mixed models (with covariates for age, sex, and level of education) were used to test the following effects: (1) we tested whether baseline scores differed between preclinical AD stage-1 and stage-2 and between subjects with prodromal AD stage-1 and stage-2 (i.e., differences in intercepts); (2) changes over time were assessed by testing whether slopes differed from 0 and whether they differed between subjects in preclinical AD stage-1 and stage-2 and between subjects in prodromal AD stage-1 and stage-2. For slope analyses, we used an unstructured covariance matrix, assuming a random intercept and fixed slope, and used follow-up time as repeated measure. We assumed a linear change in time (time coded with a quadratic term was not statistically significant). Separate analyses were performed for each criterion used to classify predementia AD. Difference with a P-value <.05 were considered to be statistically significant. Sample size was estimated for a hypothetical 3-year randomized-controlled trial with two arms, showing an expected treatment effect of 25% reduction of decline in outcome measures with a power of 80%, a two-sided alpha of 5%, and a 10% annual dropout rate using the following formula ^[25]:

with Δ as the difference in mean rate of decline in treatment versus control, σ²_e as the residual error variance of the mixed effects model, α as the type I error rate of a two-sided test and 1−β as the power, t_i as the times i at which measures were made, and t _mean as the average follow-up time. The total sample size n required for a trial was then obtained by multiplying this estimation by 2 and adjusted for an annual dropout rate of 10% over the course of 3 years (n/arm* 2 * 1.11³). Finally, we calculated the numbers needed to be screened, which is the sample size needed in a specific subgroup divided by the prevalence of this group in subjects with the same cognitive status. All analyses were stratified for baseline diagnosis.