164 Chapter 7 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. Change in amyloid status over time To evaluate amyloid accumulation over time, Figure 3 visualizes changes in amyloid status in relation to actual BPND values at baseline and follow-up, using a division into low, grey zone and high BPND. Overall, BPND in the composite ROI increased with 0.011 (SE 0.002) annually (p-value 0.00). Most individuals who were negative at baseline and at follow-up on visual rating (i.e. negative-negative) had low baseline and low follow-up BPND (54/58), and most positive-positive individuals had high baseline and high follow-up BPND (14/19). The amyloid status of 15 individuals changed over time (positive-negative n=5, negative-positive n=10). Most positive-negative individuals had both low baseline and low follow-up BPND (4/5). The group of negative-positive individuals was quite heterogeneous in terms of BPND values and had at baseline and follow-up low (4/10), grey zone (1/10) or high (1/10) BPND. Two changed from low baseline BPND to grey zone BPND at follow-up, and two changed from grey zone BPND at baseline to high BPND at follow-up. When conversely focusing on the six individuals with grey zone BPND at baseline, three belonged to the negative-positive group, two to the positive-positive group and one to the negative-negative group. This shows a considerable part of this group is on the verge of transitioning to a visually positive amyloid status.