41 ATN classification in subjective cognitive decline seven individuals, one of which progressed to AD dementia. Upon scrutinizing this patient’s chart, this diagnosis was supported by a change in biomarker status from A- to A+ (Supplemental e-Box, available from Dryad). This suggests an unusual order of pathological events, which has been described before (6, 46). In line with the proposed model of amyloid changes being among the first changes in the cascade of events eventually leading to AD dementia, earlier studies have also found amyloid positivity to be a strong risk factor for clinical progression in the clinically relevant population of individuals with SCD (11-13, 15, 47-49). In addition, we found that the effects of memory and amyloid positivity seem additive, as individuals with a low baseline memory score and positive amyloid were at the highest risk of dementia. This study has important clinical implications. There is an increasing interest in SCD as a clinically relevant construct, because these are individuals that seek help at a memory clinic. We demonstrated that within SCD, the ATN classification is associated with clinical progression and cognitive decline at a group level. Although it originally emerged as a research framework, applying ATN to SCD participants presenting to a memory clinic is a first step in evaluating the potential for translation of these criteria to clinical practice. Our results show that ATN biomarker profiles help to identify which individuals with SCD are at risk of clinical progression. But just as important, the ATN classification can help to avoid demonizing SCD as a group, because most individuals with SCD have normal biomarkers and our results show that they are highly unlikely to show cognitive decline over time. This study has some major strengths. First, we included a large cohort with almost 700 participants with SCD. We had follow-up for many, which enabled us to analyze dementia as an outcome in this initially cognitively normal sample. We used a combination of modalities to define ATN categories, which resulted in a robust classification. Among the potential limitations of this study is that we found there is an important relationship between age and biomarker abnormality. Although we corrected for age in all models used, this might not have been sufficient to completely eliminate this factor. Second, despite the fact we had a large cohort, some groups were very small. This hampered the feasibility to investigate the true value of each of the eight biomarker profiles, and furthermore illustrates that eight categories may be too large a number for practical use, while simultaneously not even capturing all heterogeneity between patients. As an additional analysis, we used the three clustered categories, clearly showing that the A+ categories are associated with an increased risk of cognitive decline and dementia. Third, inherent to using the ATN framework, we dichotomized all biomarker data. This means we used cut-off values which implies loss of information. As an alternative, it would be worth considering 2