Prognostic value of amyloid/tau/neurodegeneration (ATN) classification based on diagnostic cerebrospinal fluid samples for Alzheimer’s disease

OBJECTIVE: The primary study objective of this retrospective academic memory clinic-based observational longitudinal study was to investigate the prognostic value of a cerebrospinal fluid (CSF)-based ATN classification for subsequent cognitive decline during the 3 years following lumbar puncture in a clinical, real-life setting. The secondary objective was to investigate the prognostic value of CSF biomarkers as continuous variables. METHODS: Data from 228 patients (median age 67 (47–85) years), who presented at the Neurology Memory Clinic UZ/KU Leuven between September 2011 and December 2016, were included with a follow-up period of up to 36 months. Patients underwent a CSF AD biomarker test for amyloid-beta 1–42 (Aβ(42))(,) hyperphosphorylated tau (p(181)-tau) and total tau (t-tau) in the clinical work-up for diagnostic reasons. Patients were divided into ATN classes based on CSF biomarkers: Aβ(42) for amyloid (A), p(181)-tau for tau (T), and t-tau as a measure for neurodegeneration (N). Based on retrospective data analysis, cognitive performance was evaluated by Mini Mental State Examination (MMSE) scores every 6 months over a period up to 36 months following the lumbar puncture. The statistical analysis was based on linear mixed-effects modeling (LME). RESULTS: The distribution in the current clinical sample was as follows: A−/T−/N− 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+ 1.32% (3 cases), with no cases in the A−/T+/N− and A+/T+/N− class. Hence, the latter 3 classes were excluded from further analyses. The change of MMSE relative to A−/T−/N− over a 36-month 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 was seen in the A+/T+/N+ class at 12 months after baseline. The effect of ATN class on future cognitive decline was confirmed for a different set of CSF thresholds. All individual baseline CSF biomarkers including the Aβ(42)/t-tau ratio showed a significant correlation with subsequent cognitive decline, with the highest correlation seen for Aβ(42)/t-tau. CONCLUSION: ATN 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-021-00817-4.