P1-166: CSF biomarkers predict conversion to dementia in mild cognitive impairment

In order to investigate whether the cerebrospinal fluid (CSF) biomarkers β-amyloid protein (Aβ1–42), total tau protein (T-tau) and tau phosphorylated at threonine 181 (P-tau181P) can predict conversion to dementia in mild cognitive impairment (MCI), we set up a prospective, longitudinal study. Seventy-five MCI patients were included. CSF was collected by means of lumbar puncture at baseline. Clinical follow-up was scheduled at least semi-annually. A follow-up diagnosis of MCI (stable MCI) or dementia (converting MCI) was made by a neurologist using strictly applied clinical diagnostic criteria. CSF biomarker levels of Aβ1–42, T-tau and P-tau181P were determined with commercially available single-parameter ELISA kits. Optimal cut-off values of individual CSF biomarkers for discriminating dementia from controls were determined using ROC curves in a population of 152 neuropathologically confirmed dementia patients and 99 healthy controls. CSF concentrations of Aβ1–42≤587 pg/mL, T-tau≥270 pg/mL and P-tau181P≥39 pg/mL were considered pathological. MCI patients were divided into two categories: those with normal (pathological level for ≤1 biomarker) and with pathological (pathological levels for ≥2 biomarkers) biomarker profiles. Mean follow-up period was 15,5±15,3 months. At follow-up, 36 (48%) MCI patients converted to dementia of which 22 (29%) converted to Alzheimer's disease (AD). Of all converting MCI patients, 28/36 (78%) had pathological CSF biomarker profiles. Including only non-converting MCI patients and MCI patients converting to AD, 18/22 (82%) had pathological CSF profiles. Considering the MCI subgroup with pathological CSF (n=52), 28/52 patients (54%) converted to dementia during the study. Considering MCI patients with normal CSF at baseline (n=23), 15/23 patients (65%) remained stable during the study. The CSF biomarkers Aβ1–42, T-tau and P-tau181P predict conversion to dementia in MCI as 78% of converting MCI patients had pathological CSF biomarker profiles at baseline, defined as pathological levels for at least two out of three biomarkers.