171 Longitudinal change in biomarkers negative slope in some individuals, but did not address the possibility of reverting amyloid status and explained the negative slope by random variation, noise, or actual clearance of amyloid (7, 8). One potential explanation for the five individuals changing from a positive to negative amyloid status by visual rating (positive-negative) could be that these scans were false-positive at baseline. While the quantitative measures might not have changed much over time, scan could be visually assessed differently at the two time points due to an imperfect intra-rater agreement (20-22). This is part of clinical practice, especially in early disease stages. Therefore, acquiring followup scans is highly useful in individuals with equivocal scans with grey zone amyloid burden. Of note, one could also argue that also the negative-positive scans could be the result of rater variability, and that their changing from negative to positive does not necessarily reflect clinical relevance. However, a substantial portion of these individuals had grey zone amyloid burden at baseline, which is already associated with a changed slope in memory function, as shown by our group previously (6). We found that this group has a steeper decline in performance on Stroop I and III, which are indicative of attention and executive functioning. This is in line with other studies showing that amyloid burden in the subthreshold range is associated with cognitive decline and highlights the clinical relevance of grey zone amyloid burden (7, 8). In general, an amyloid status based on visual assessment is not identical to an amyloid status based on a threshold for quantitative measures. Quantitative measures are not directly affected by rater variability and could therefore be interpreted as more consistent. However, quantitative measures of amyloid burden are often averaged over a larger ROI. If a scan is visually assessed as A+ based on a relatively small area, this does not necessarily translate in a higher average BPND in the total ROI, which could be a potential cause of differences between the two approaches. Overall, we found a relatively high degree of changing biomarkers in a short time frame. These results add to the literature suggesting the clinical relevance of changing from a negative to a positive amyloid status. When we compared ATN profiles over time, we found 44% of individuals changed to a different ATN profile during 2.5 years of follow-up. Data on changing biomarkers enable the evaluation of the actual sequence of biomarker abnormality. Of note, most (11/17) individuals followed a different sequence than the overall accepted hypothesis of A becoming abnormal first, then T and N last (2). In our sample, individuals changed to T+ or N+ while still being A-, or changed to N+ before T+. These findings are in line with those of a former study investigating change in ATN profiles, which also found multiple sequences (5). There are several possible explanations for these observations. First, amyloid could already be accumulating in the subthreshold range in individuals changing to T+ or N+, but before A+, suggesting the pathological process 7
RkJQdWJsaXNoZXIy MjY0ODMw