82 Chapter 4 otherwise the addition of N would have no added value in the AT(N) classification. Furthermore, if different N biomarkers indeed capture the same process, correlations between N biomarkers should be higher than correlations between A and N, or T and N biomarkers. Finally, as N provides staging information, it should have some clinical correlate. In early disease stages especially, it is important to be able to accurately predict future deterioration, for both the individuals themselves and clinical trial recruitment, since these could still potentially benefit from disease modifying therapies. Therefore, our aims were (1) to compare the different N biomarkers CSF total (t)-tau, medial temporal atrophy (MTA) visual rating on MRI, hippocampal volume (HV), serum neurofilament light (NfL) and serum glial fibrillary acidic protein (GFAP) to each other and to markers of A and T, and (2) to determine their predictive value for clinical progression and cognitive decline beyond A and T, in a sample of cognitively normal individuals with subjective cognitive decline (SCD). METHODS Study population We included 401 individuals with SCD from the Amsterdam Dementia Cohort (ADC) and SCIENCe project (Subjective Cognitive Impairment Cohort) (16, 17). The SCIENCe project is a substudy of ADC and prospectively follows individuals with SCD. Individuals were referred to our memory clinic because of cognitive complaints by their general physician, a geriatrist or a neurologist, and underwent an extensive diagnostic workup, including a physical, neurological and neuropsychological evaluation. In a multidisciplinary consensus meeting, all individuals received the label SCD when they performed within normal limits on a neuropsychological assessment, and criteria for mild cognitive impairment (MCI), dementia, or other neurological or psychiatric diseases that could potentially cause cognitive complaints, were not met. At follow-up, diagnoses were re-evaluated as SCD, MCI, AD dementia or other types of dementia. Clinical progression was defined as progression from SCD to MCI or dementia. Inclusion criteria for the current study were baseline SCD diagnosis, availability of follow-up information (≥ 2 diagnoses), availability of CSF, and availability of MRI and/or serum biomarkers within one year of diagnosis. MMSE was assessed annually and was used as longitudinal measure of global cognition. Education was rated using the Dutch Verhage system (18). Biomarkers We used all biomarkers both as continuous and dichotomous measures. We used CSF Aβ (continuous and dichotomous, abnormal <813 pg/mL) or amyloid PET (dichotomous,
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