AbstractBackgroundAs first objective, we examined in a clinical, real‐life setting, the prognostic value of cerebrospinal fluid (CSF) based Amyloid Tau Neurodegeneration (ATN) classification for subsequent cognitive decline during the three years following a lumbar puncture. The secondary objective was to investigate the prognostic value of CSF biomarkers as continuous variables.MethodRetrospective data from an academic memory clinic sample of 228 patients (median age 67 (47‐85) years) were retrieved. CSF data (Innotest assays) were available in all patients and used for ATN classification: the cut‐off values were 798 pg/mL for amyloid‐beta 1‐42 (Aβ42) (A), 87 pg/mL for hyperphosphorylated tau (p181‐tau) (T), and 465 pg/mL for total tau (t‐tau) (N). A secondary analysis with ATN based on lower tau cut‐offs (p181‐tau: 58.9 pg/ml; t‐tau: 354 pg/ml) was also applied. Cognitive performance was evaluated by Mini Mental State Examination (MMSE) every 6 months over a period up to 36 months following the lumbar puncture. Linear mixed‐effects modelling was performed on non‐imputed data (minimum 3 MMSE scores) as well as on imputed data using the R packages ‘nlme’ and ‘mice’.ResultIn the current sample, classification showed 32.02% A‐/T‐/N‐, 33.33% A+/T‐/N‐, 17.11% A+/T+/N+, 11.84% A+/T‐/N+, 4.39% A‐/T‐/N+ and 1.32% A‐/T+/N+ (3 cases), with the A‐/T+/N‐ and A+/T+/N‐ class being absent. Hence the latter 3 classes were excluded from further analyses. The change of MMSE relative to A‐/T‐/N‐ over a 36 months period was significant in all four ATN classes: A+/T+/N+ = ‐4.78 points on the MMSE; A‐/T‐/N+ = ‐4.76; A+/T‐/N+ = ‐2.83; A+/T‐/N‐ = ‐1.96. The earliest significant difference in slope was seen in the A+/T+/N+ class at 12 months after baseline (Figure 1A). The effect of ATN class on future cognitive decline was confirmed for a different set of CSF thresholds (Figure 1B). All individual baseline CSF biomarkers including the Aβ42/t‐tau ratio showed a significant correlation with subsequent cognitive decline, with the highest correlation seen for Aβ42/t‐tau.ConclusionATN classification based on CSF biomarkers has a statistically significant and clinically relevant prognostic value for the course of cognitive decline in a 3‐year period in a clinical practice setting.