213 Longitudinal change in ATN biomarkers ATN biomarkers over time We first examined changes in A, T, and N biomarkers individually. Figure 1 shows changes in biomarker status over time. Several individuals changed from negative to positive status (A: n = 10 (11%); T: n = 6 (14%); N: n = 7 (9%)). For A and N but not for T, a smaller number of individuals changed from a positive to a negative status (A: n = 5 (5%); N: n = 4 (5%)). For individuals with complete biomarker information for A, T, and N at two time points (n = 39), Figure 2 visualizes the trajectory of ATN profiles from baseline to follow-up. During follow-up, 17 (44%) changed to another ATN profile. The percentage of individuals with normal AD biomarkers changed from 62% at baseline to 46% at follow-up. Five percent of individuals fell within the category of non-AD pathologic change at baseline, which changed to 18% at follow-up. The percentage of individuals with biomarkers in the Alzheimer’s continuum changed from 33% at baseline to 36% at follow-up. According to the most common model of the pathophysiology of AD, the expected sequence of biomarkers becoming abnormal would be A → T → N. Only six of the 17 individuals changing profile fit into this hypothetical sequence. The other eight changed to T+ or N+ while still being A−, or changed to N+ before T+. Finally, three participants changed to a better ATN profile (A−T−N+ → A−T−N− n = 1, A+T−N− → A−T−N− n = 2). During the period of follow-up, three individuals showed clinical progression; to dementia with Lewy bodies (DLB) n = 1, MCI due to AD n = 1, and AD dementia n = 1. The individual who progressed to DLB changed from A−T−N− to A+T−N−.The individual who progressed to MCI due to AD had the A+T−N− profile at baseline and at follow-up. The individual who progressed to AD dementia changed from baseline A+T+N− to A+T+N+. The last two individuals both carried an APOE ε4 allele. 8
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