27 ATN classification in subjective cognitive decline standardized residuals with values < -1.96 or > 1.96 considered significant. We used Chi-squared test to compare the distribution of ATN profiles between the SCD and control group. We performed Cox proportional hazards analyses to evaluate the association between eight-profile ATN classification (A-T-N-: reference) and clinical progression to dementia. Analyses were adjusted for age, sex and education. In additional analyses, we used progression to MCI or dementia as outcome. To explore the additive effect of A-status and memory function, we ran an additional analysis after constructing a new, four-level variable ((1) A-, high memory (baseline RAVLT-delayed recall z-score ≤ -1.0); (2) A-, low memory (z-score > -1.0); (3) A+, high memory; (4) A+, low memory). Analyses were adjusted for age, sex and education. As reference category we used (1) A-, high memory. Subsequently, we assessed the associations between ATN classification and cognitive decline using linear mixed models (LMM). ATN profiles (included as dummies, with the A-T-N- profile as reference), time and the interactions between ATN profiles and time were included as independent variables, age, sex and education were included as covariates, and cognitive test scores were used as dependent variables. Intercept and time were included as random factors. Separate models were run for 11 individual neuropsychological tests. We used the false discovery rate (FDR) method to correct for multiple testing with q set at 0.05. For the analyses in the control group without SCD, we additionally added family as a random factor to account for within twin pair dependence. All analyses were done using SPSS version 22. P-values <0.05 were considered significant. Kaplan Meier curves and figures showing association between ATN and cognitive decline were made with R studio 3.4.2. Data availability Any data not published within the article may be shared upon request. 2
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