170 Chapter 7 Table 4. Associations between change in amyloid burden and cognitive test performance (continued) Baseline Longitudinal Positivenegative Negativepositive Positivepositive Positivenegative Negativepositive Positivepositive Stroop III 0.12 (0.09) 0.01 (0.06) 0.02 (0.05) -0.01 (0.02) -0.03 (0.01)* -0.02 (0.01)* MMSE -0.23 (0.48) 0.06 (0.34) -0.29 (0.26) -0.14 (0.18) 0.01 (0.11) -0.06 (0.08) Data is presented as beta (SE) as estimated by linear mixed models. Models included a four level variable indicating change in amyloid status (negative-negative (reference), negative-positive, positive-negative and positive-positive), time and their interaction as predictors. All models were adjusted for age, sex and education. Outcome was cognitive test performance. Baseline estimates represent the association between the predictor and baseline test performance, longitudinal estimates represent the association of the interaction between predictor and time, and reflect the slope of cognitive test performance. VAT = visual association test, RAVLT = rey auditory verbal learning task, TMT = trail making test, MMSE = mini mental state examination. * p < 0.05. DISCUSSION In our sample of cognitively normal individuals with SCD, we found that biomarker abnormality increased over a 2.5 year period. There was considerable variability in the order of biomarkers becoming abnormal in the ATN classification, suggesting no fixed order. Change from A- to A+ was associated with steeper decline in tests of attention and executive function. We showed that the number of individuals with an abnormal biomarker status increased for both A, T and N, over a time course of 2.5 years. Most of these individuals changed from a negative to positive biomarker status, yet of note, a smaller number of individuals changed from positive to negative. There are not many longitudinal studies investigating changes in the ATN classification, hence the phenomenon of change from a positive to a negative status has not yet received much attention. One study investigating amyloid burden excluded individuals who were amyloid positive at one time point, and negative at the next, but did not specify the number of individuals (9). Another excluded the 5% of individuals with borderline amyloid PET burden, reducing the risk of individuals crossing the threshold due to small changes (5). Other studies investigating amyloid accumulation rate as continuous measure showed a
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